Statins beyond seventy

what STAREE will and will not answer

STAREE randomised almost 10,000 healthy Australians aged 70 and over to atorvastatin or placebo, with disability-free survival as its primary endpoint. Presented in Hot Line 2 at ESC Congress 2026, it addresses the largest remaining evidence gap in primary prevention: whether statins help healthy older adults live longer without disability or dementia. Either outcome will directly change everyday consultations about starting, or stopping, statins in older age.

The new ESC heart failure guideline

what lands on 28 August

The new ESC heart failure guideline, the first full revision since 2021, is presented on Friday 28 August at ESC Congress 2026, followed by an Ask the Task Force session. Expect consolidation of four-pillar HFrEF therapy and its rapid initiation, a firmer evidence base for HFpEF treatment, and close alignment with the simultaneously released guideline on cardiovascular disease and chronic kidney disease.

Heart and kidney in one guideline

why the ESC now treats them together

ESC Congress 2026 delivers the first dedicated ESC guideline on cardiovascular disease in chronic kidney disease, presented Saturday 29 August. It formalises care for a huge overlap population long excluded from trials, arriving exactly as SGLT2 inhibitors, finerenone and GLP-1 agonists have turned cardio-renal protection into a treatable continuum.

Factor XI inhibition

the hypothesis, the promise and the LIBREXIA ACS lesson

Factor XI inhibition promises antithrombotic effect without the bleeding cost, but the field keeps hitting reality: after asundexian, the 14,000-patient LIBREXIA ACS trial of milvexian was halted for futility in November 2025. The full results, presented at ESC Congress 2026, will determine what remains of the factor XI hypothesis in ACS, while the AF and stroke programmes continue.

Peptide hormone-based combinational pharmacotherapies for chronic metabolic diseases.

This narrative review evaluates the pharmacological and clinical advances of combination therapies using peptide hormone co-agonists, such as GLP-1 combined with FGF21 or GDF15 analogs, for chronic metabolic diseases including obesity, type 2 diabetes, MASLD, and cardiovascular disease. The authors highlight that synergistic targeting of multiple metabolic pathways yields superior efficacy over monotherapy, addressing the growing burden of metabolic multimorbidity. For clinicians, these findings outline the evolving therapeutic landscape and underscore the potential of next-generation co-agonists to transform cardiometabolic care, while noting ongoing challenges in clinical development and safety profiling.

Systolic blood pressure and albuminuria reduction mediate cardiovascular benefits of finerenone in T2 diabetes and CKD.

A causal mediation analysis of the pooled FIDELITY trial data (n = 12,143) demonstrates that the cardiovascular benefit of finerenone in patients with type 2 diabetes and chronic kidney disease is largely driven by early reductions in urine albumin-to-creatinine ratio (UACR) and systolic blood pressure. Within four months, UACR and systolic blood pressure changes accounted for 39% and 21% of the long-term cardiovascular risk reduction, respectively, while shifts in body weight and serum potassium did not mediate outcomes. These findings highlight UACR and blood pressure as complementary early markers to monitor cardiovascular efficacy when initiating finerenone therapy.

Blood Pressure Control and Mortality Among US Veterans

Intensive blood-pressure lowering reduces mortality and cardiovascular disease in clinical trials, but real-world BP measurements often differ from standardised protocols. In this retrospective cohort of over 2.3 million US Veterans with hypertension (mean age 66; 36% diabetes, 22% cardiovascular disease, 19% kidney disease), systolic BP was treated as a time-dependent variable across seven categories. Lowest mortality was seen at a systolic BP of 130-139 mmHg. Compared with a year at BP ≥160 mmHg, adjusted hazard ratios included 1.29 at <110, 0.83 at 130-139 and 0.86 at 140-149 mmHg — a J-shaped relationship consistent across patients with and without cardiovascular or kidney disease. In routine practice, a somewhat higher BP target thus appears appropriate, especially for older patients with comorbidity.

Sex differences in risk factor control and medication adherence post-ACS

insights from the TEXTMEDS randomised clinical trial

Good risk-factor control and medication adherence after an acute coronary syndrome (ACS) help determine long-term prognosis, and sex plays a role. In this secondary analysis of the randomised TEXTMEDS trial (1,379 patients post-ACS, 79% male), sex differences in secondary-prevention targets were examined. Women were less likely to reach the LDL-cholesterol target (<1.8 mmol/L; aOR 0.61) and to exercise regularly (aOR 0.61), but more likely to achieve a healthy BMI (aOR 1.47). Women were also less adherent to medication (aOR 0.68), though this association weakened and lost significance after adjustment for socioeconomic factors. The findings argue for sex-sensitive strategies for risk-factor control and adherence to improve cardiovascular outcomes.

Frailty and Heart Failure

An Integrated Review of a Bidirectional Relationship.

This integrated review examines the bidirectional relationship between frailty and heart failure in older adults, highlighting how frailty independently predicts incident HF while HF accelerates frailty progression through inflammation, sarcopenia, and deconditioning. Frailty is strongly associated with higher mortality, reduced quality of life, and poorer tolerance of guideline-directed medical therapy, with the newly proposed Heart Failure Frailty Score (HFFS) offering a dedicated assessment tool. Clinically, routine frailty screening and targeted interventions—including exercise rehabilitation, nutritional support, and structured medication review—are essential to optimise outcomes in this vulnerable population.

AHA/ACC/ESC/WHF Expert Consensus Document

Second Universal Definition of Heart Failure (2026).

A joint expert consensus from the AHA, ACC, ESC, and WHF introduces the second universal definition of heart failure to resolve longstanding diagnostic ambiguities and standardize global surveillance. The updated framework replaces rigid left ventricular ejection fraction cutoffs with dynamic categories of reduced, preserved, and improved ejection fraction, while formally integrating pre-heart failure (stage B), recovery trajectories, and social determinants into clinical classification. This standardized nomenclature will streamline early detection, guide prevention strategies, and align research and practice across primary care, cardiology, and health systems worldwide.

Antithrombotic Management in Patients with Chronic Coronary Syndrome Receiving Oral Anticoagulation.

A recent narrative review synthesizes evidence on antithrombotic management in patients with stable chronic coronary syndrome (CCS) and atrial fibrillation (AF). Trials including AFIRE, EPIC-CAD, AQUATIC, and ADAPT-AF-DES demonstrate that oral anticoagulant (OAC) monotherapy is superior to combination therapy with antiplatelets, resulting in significantly fewer major bleeding events without an increase in ischemic complications, and even showing excess mortality with prolonged combination regimens. For clinical practice, this supports OAC monotherapy as the preferred long-term strategy, effectively balancing ischemic protection with bleeding risk reduction.

Trends in nephrology

from "supportive care" to CKD combination therapy.

This narrative review outlines the shift in chronic kidney disease (CKD) management from renin-angiotensin system inhibitor monotherapy to a four-pillar combination approach incorporating SGLT2 inhibitors, GLP-1 receptor agonists, and nonsteroidal mineralocorticoid receptor antagonists. Evidence and the 2024 KDIGO guidelines indicate that these complementary therapies significantly reduce kidney failure risk in diabetic patients while improving safety and tolerability, notably by mitigating hyperkalemia. Clinicians should consider early integration of this multimodal strategy, with ongoing research focusing on non-diabetic CKD populations and novel agents like aldosterone synthase inhibitors.

Association between C reactive protein and risk of incident heart failure in cancer survivors

Cancer survivors are at risk of heart failure (HF), partly from prior cancer therapy, but early predictors are scarce. Chronic low-grade inflammation has been linked to both cancer and HF. In this UK Biobank analysis (20,244 participants with cancer at baseline, mean age 60), 2.0% developed incident HF over a median 10.5-year follow-up. After adjustment for sociodemographic, lifestyle and clinical factors, CRP above 2 mg/L was associated with a 53% higher HF risk (sHR 1.53). Subgroup analyses confirmed this trend, which was strongest among survivors of cutaneous malignancies. A simple inflammatory marker may thus help identify cancer survivors at elevated HF risk; future research should determine whether reducing inflammation lowers that risk.

Early outcomes and predictors of mortality in native aortic valve endocarditis

results from a national registry

Native aortic valve endocarditis is often complicated by heart failure, peri-annular extension and conduction disturbances, making surgery challenging. In this retrospective analysis of the UK NICOR registry, 3,694 patients underwent aortic valve replacement (AVR) for endocarditis (1996-2019; mean age 58, 22% female). In-hospital mortality was 7.8%. Non-survivors were older and more often had chronic kidney disease, diabetes, pulmonary disease, cardiogenic shock and poor ventricular function. On multivariable analysis, operative urgency (OR 2.49) and preoperative inotropic support (OR 2.24) were the strongest predictors of mortality, alongside NYHA III-IV, age, kidney disease and atrial fibrillation. More recent years of surgery were associated with better survival. Surgery for aortic valve endocarditis thus remains high risk, though outcomes have improved over time.

Sex differences in the diagnosis, management and outcomes of patients with infective endocarditis

Although interest in male-female differences in cardiovascular disease is growing, evidence in infective endocarditis (IE) is limited and contradictory. This prospective study included 791 patients with definite or possible IE discussed by the endocarditis team (2016-2025; 73% male, 27% female). Women more often had mitral-valve IE, men more often aortic-valve IE, more predisposing conditions and more Cutibacterium. Although the indication for surgery did not differ, men were operated on more often (41% vs 29%), and women with a surgical indication were more often treated conservatively (37% vs 23%). Over a median 2.1-year follow-up, women had higher adjusted mortality (HR 1.39); after excluding non-operated patients with an indication, surgery appeared more protective in women than men. The findings point to sex differences in surgical decision-making and a less favourable prognosis in women.

Transseptal puncture in cardiovascular interventions

a clinical consensus statement of the European Heart Rhythm Association, the Heart Failure Association, the European Association of Percutaneous Cardiovascular Interventions, the European Association of Cardiovascular Imaging of the ESC, and the Association for European Paediatric and Congenital Cardiology.

A multi-society ESC working group has released a clinical consensus on transseptal puncture (TSP), a foundational technique for over 250,000 annual atrial fibrillation ablations and various structural heart interventions. The statement emphasizes the critical role of echocardiographic guidance for precise fossa ovalis targeting, outlines standardized techniques, and provides clear algorithms for preventing and managing life-threatening complications such as cardiac tamponade and aortic puncture. This consensus offers interventional cardiologists and electrophysiologists a practical, evidence-based framework to enhance procedural safety and outcomes across routine and complex cases.

Chronotype-aligned exercise timing in middle-aged adults at cardiometabolic risk

a randomised controlled trial.

Aligning the timing of exercise with chronotype ('morning' or 'evening' type) may yield greater cardiometabolic benefit. In this 12-week randomised trial (Lahore, Pakistan; 150 sedentary adults aged 40-60 with at least one cardiovascular risk factor), chronotype was determined by questionnaire and confirmed with 48-hour core body-temperature monitoring. Participants trained supervised (5×/week, 40 min moderate intensity) either at their preferred time (chronotype-aligned, CAE) or at their non-preferred time (CME). The CAE group improved significantly more in systolic blood pressure (-10.8 vs -5.5 mmHg), diastolic blood pressure, heart-rate variability (RMSSD), peak VO2, LDL, fasting glucose and sleep quality (PSQI). Matching exercise to individual chronotype could thus be a low-cost, personalised way to improve cardiovascular health.

Lipid management in type 2 diabetes and non-HDL-cholesterol

target all atherogenic lipoproteins.

Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality in diabetes, partly driven by dyslipidaemia. Although LDL cholesterol (LDL-C) is the primary treatment target, many patients with diabetes have mixed dyslipidaemia with elevated triglycerides and atherogenic remnant lipoproteins, better captured by non-HDL cholesterol (non-HDL-C). Guidelines from the ADA, AACE and ESC recommend both LDL-C and non-HDL-C targets based on individual risk, yet target attainment remains suboptimal in practice. Statins, ezetimibe, bempedoic acid and PCSK9 inhibitors effectively lower LDL-C and non-HDL-C and reduce cardiovascular risk; triglyceride-lowering agents (omega-3, fibrates) lower triglycerides but their effect on hard outcomes remains uncertain. This review argues for using non-HDL-C and apolipoprotein B (apoB) alongside LDL-C as measures of atherogenic burden, and for more targeted treatment of residual atherogenic particles in diabetes.

New kidneys, old risks

cardiovascular challenges after transplantation.

Kidney transplantation significantly improves survival, yet cardiovascular disease remains the leading cause of morbidity and mortality in transplant recipients. This review highlights how traditional risk factors, immunosuppressive therapies, and post-transplant metabolic complications sustain a high cardiovascular burden, while evidence for targeted interventions remains largely extrapolated from non-transplant populations. For clinical practice, this underscores the need for rigorous risk stratification and cautious adoption of emerging cardiorenal therapies like SGLT2 inhibitors and GLP-1 receptor agonists, alongside a strong push for transplant-specific randomized trials.

Combined effect of educational attainment and diabetes on 1-year all-cause mortality in heart failure patients

findings from the National Heart Failure Registry, India.

Patients with both heart failure (HF) and diabetes are often prescribed complex regimens, but their impact may depend on social determinants such as educational attainment. This analysis of India's National Heart Failure Registry (10,850 patients, 53 hospitals, 21 states) followed patients for one year. Cumulative 1-year mortality was 22.1%. Diabetes was associated with 10% higher mortality (HR 1.10), and higher education independently with lower mortality. Compared with patients without diabetes and low education, those with both diabetes and low education had 25% higher risk of death (HR 1.25), whereas those with diabetes and higher education had 22% lower risk (HR 0.78). A significant interaction was found: the adverse effect of diabetes is greater among the less educated. The findings underscore the importance of health literacy and equitable access to care to reduce disparities in heart failure.

Epidemiology, economic burden and mortality of atrial fibrillation in a region with very high life expectancy

a contemporary, population-based analysis in Catalonia.

The high prevalence of atrial fibrillation (AF) is a public-health challenge, especially in ageing societies. This retrospective population-based study used the Catalan public health system database (8 million people, 2019-2023). Age-standardised AF prevalence remained stable at 2.5%, while incidence fell slightly (from 3.8 to 3.6 per 1,000). The 2023 AF population had a median age of 77.6 years and a high comorbidity burden: heart failure (37.6%), obesity (33.8%) and coronary disease (26.7%). Low socioeconomic status was associated with higher AF prevalence. AF was modestly associated with all-cause mortality (OR 1.25), and its healthcare costs were estimated at 2% of the annual Catalan health budget. In a high-life-expectancy region, AF prevalence thus appears to be plateauing, with a high disease burden and substantial economic impact.

Phenotyping patients with a low-flow, low-gradient aortic stenosis and a preserved ejection fraction undergoing TAVI.

In a cohort of 827 patients undergoing TAVI, unsupervised clustering of AI-assessed echocardiographic parameters identified two distinct phenotypes among the 35% with paradoxical low-flow, low-gradient aortic stenosis and preserved ejection fraction. Patients exhibiting a HFpEF and atrial fibrillation phenotype faced a significantly higher risk of cardiovascular mortality and heart failure hospitalisation at 1 and 5 years. These findings suggest that targeted guideline-directed medical therapy for HFpEF, including SGLT2 inhibitors and MRAs, may improve outcomes in this high-risk subgroup.

Assessment and management of cardiovascular-kidney-liver metabolic-syndrome in the primary care setting

A multidisciplinary consensus statement.

The recently introduced cardiovascular-kidney-metabolic (CKM) syndrome captures the close interplay between metabolic risk factors, chronic kidney disease and cardiovascular disease, but underestimates the role of the liver. Metabolic dysfunction-associated steatotic liver disease (MASLD) — the world's most prevalent chronic liver disease — is strongly linked to cardiovascular events, kidney-disease progression and mortality, yet is often missed in practice. This multidisciplinary consensus statement proposes the concept of a cardiovascular-kidney-liver-metabolic syndrome (CKLMS) and offers a practical, primary-care-centred framework. Using accessible, validated tools — blood pressure and lipid profiling, kidney function and albuminuria, non-invasive liver fibrosis testing, and screening for diabetes and obesity — cardiovascular, renal, hepatic and metabolic risk are stratified together. It emphasises early lifestyle intervention, drugs with multi-organ benefit, and clear referral pathways, positioning the primary-care physician as coordinator of longitudinal, patient-centred care.

Patient Care Pathways and Outcomes Following Newly Diagnosed Atrial Fibrillation.

Care pathways in atrial fibrillation (AF) are poorly characterised and may influence guideline-concordant treatment. In the Optum database (37,370 patients with incident AF, 2015–2023), 20.6% had a pathway including an electrophysiologist visit. Older patients and those with a higher CHA2DS2-VASc score were less likely to see an electrophysiologist. An electrophysiologist visit was associated with more antiarrhythmic therapy and oral anticoagulation, and in patients aged 80+ with lower stroke risk (HR 0.63). Guideline-concordant care and better outcomes — especially in the highest stroke-risk groups — were thus associated with electrophysiology pathways, even though high-risk groups received that care less often.

Sex Differences in Outcomes After Breakthrough Ischemic Stroke on Oral Anticoagulants for Atrial Fibrillation

An ASPERA-R Inverse Probability Weighted Analysis.

Sex-specific outcomes after breakthrough ischaemic stroke on oral anticoagulation (OAC) in atrial fibrillation were unknown. In the international retrospective ASPERA-R study (1,649 patients, 52% women, mean age 78), women were older and had more severe baseline impairment. After inverse-probability weighting, women were less likely to return to baseline neurologic function (35.2% vs 42.7%; adjusted RR 0.82), had a worse mRS distribution and more recurrent stroke/TIA (adjusted HR 1.70), with a trend toward more major bleeding. Significant sex interactions were seen for OAC type, endovascular treatment and OAC restart. The findings argue for sex-aware management.

Lipoprotein(a), High-Sensitivity C-Reactive Protein, and Incident ASCVD Risk in Individuals Without Standard Modifiable Risk Factors.

The combined value of lipoprotein(a) [Lp(a)] and high-sensitivity CRP (hsCRP) in primary prevention among people without standard modifiable risk factors (SMuRF-less: no smoking, obesity, hypertension, dyslipidaemia or diabetes) was unclear. In 50,450 SMuRF-less UK Biobank participants, 1,104 (2.2%) ASCVD events occurred over 15 years. Both elevated hsCRP (sHR 1.35) and elevated Lp(a) (sHR 1.24) were independently associated with ASCVD; risk was highest with concurrent elevation of both (sHR 1.64, and 1.74 using clinical cutoffs Lp(a) ≥125 nmol/L and hsCRP ≥2.0 mg/L). Combined Lp(a) and hsCRP assessment thus provides complementary risk information, even in apparently low-risk individuals.

Blood Pressure Control and Mortality Among US Veterans

Intensive blood-pressure lowering reduces mortality and cardiovascular disease in clinical trials, but real-world BP measurements often differ from standardised protocols. In this retrospective cohort of over 2.3 million US Veterans with hypertension (mean age 66; 36% diabetes, 22% cardiovascular disease, 19% kidney disease), systolic BP was treated as a time-dependent variable across seven categories. Lowest mortality was seen at a systolic BP of 130-139 mmHg. Compared with a year at BP ≥160 mmHg, adjusted hazard ratios included 1.29 at <110, 0.83 at 130-139 and 0.86 at 140-149 mmHg — a J-shaped relationship consistent across patients with and without cardiovascular or kidney disease. In routine practice, a somewhat higher BP target thus appears appropriate, especially for older patients with comorbidity.

Kidney Dysfunction and Pulmonary Vascular Disease in Heart Failure with preserved Ejection Fraction.

Chronic kidney disease (CKD) is common in heart failure with preserved ejection fraction (HFpEF) and is linked to worse outcomes via unclear mechanisms. In this cohort of 925 HFpEF patients undergoing invasive haemodynamic exercise testing (34.5% with eGFR <60), worse kidney function was associated with higher biventricular filling pressures, lower cardiac output and — most strikingly — increasing pulmonary vascular disease: pulmonary vascular resistance rose and pulmonary arterial compliance fell as kidney function declined. During exercise these differences became even more pronounced, with the greatest cardiac-output limitation in the worst kidney function. CKD thus contributes to progressive pulmonary vascular disease in HFpEF.

Multi-Organ Physiologic Deficits During Exercise Identify Clinical and Molecular Predisposition to Heart Failure with Preserved Ejection Fraction

Exercise unmasks the limited multi-organ reserve characteristic of heart failure with preserved ejection fraction (HFpEF). Using invasive cardiopulmonary exercise testing (iCPET), metabolite profiling and genomics, the investigators characterised seven exercise physiologic deficits in HFpEF patients: reduced exercise stroke volume and heart rate, a steep PCWP/cardiac-output slope, elevated pulmonary vascular resistance, pulmonary mechanical limitation, impaired peripheral oxygen extraction, and the obesity-related exaggerated metabolic cost of exercise. They mapped the distribution and the functional and prognostic significance of these deficits and linked them to molecular (metabolite and genetic) signatures — a step toward more targeted HFpEF phenotyping and risk assessment.

The Natural History of Massive Left Ventricular Hypertrophy in Pediatric Hypertrophic Cardiomyopathy

A Multiregistry Analysis

Massive left ventricular hypertrophy (LVH) is a risk factor for sudden cardiac death in children with hypertrophic cardiomyopathy (HCM), but its natural history is poorly understood. This analysis from two large international registries (SHaRe and IPHCC) compares children with HCM with and without massive LVH — defined as maximal wall thickness ≥30 mm or a z-score ≥+20 before age 18 — using serial wall-thickness measurements and composite outcomes for major ventricular arrhythmia events (sudden cardiac death, aborted sudden cardiac death or appropriate ICD therapy) and heart failure. The study characterises the course and risk profile of this severe phenotype to support risk stratification and treatment decisions such as ICD implantation.

New-onset postoperative atrial fibrillation management and outcomes

the VISION Cardiac Surgery cohort.

In the prospective VISION Cardiac Surgery cohort (12,234 patients, 12 countries), new-onset postoperative atrial fibrillation (POAF) occurred in 31.8% within 30 days of cardiac surgery. Antithrombotic and antiarrhythmic management varied widely: 15.6% received anticoagulation alone, 54.3% antiplatelets alone, 24% both, and 49% amiodarone. At one year, clinical AF was detected in 6.9% of POAF patients versus 0.6% without (aHR 11.3), and all-cause mortality was higher (3.0% vs 1.7%; aHR 1.54). POAF after cardiac surgery is thus common and associated with both more AF and higher mortality in the first year.

Development of an Integrated Monogenic and Polygenic Risk Assessment Tool for Coronary Artery Disease and Its Application in a Community-Based Health Care Biobank.

Current genetic testing for coronary artery disease (CAD) mainly targets monogenic variants in severe hypercholesterolaemia. GenProbCAD combines monogenic pathogenic variants with polygenic risk scores for CAD and for lipoprotein(a), developed and validated in the UK Biobank (two cohorts of 226,145) and applied in a community biobank (20,477). The integrated score predicted CAD better than monogenic variants or the polygenic score alone and flagged 16% as high-risk — 46-fold more than monogenic carriers — with comparable CAD prevalence and consistent prediction across all LDL strata and ancestries. A universal strategy would hypothetically capture ~21% of all incident CAD, versus 0.3% with current monogenic testing.

PCSK9 inhibitor treatment and outcomes in patients with atherosclerotic cardiovascular disease but without prior ischaemic events

an observational study.

This real-world study (Optum database; 19,670 patients with atherosclerotic cardiovascular disease and no prior ischaemic event) compared PCSK9 monoclonal-antibody initiators with matched non-initiators. Over five years, the composite of non-fatal myocardial infarction, non-fatal ischaemic stroke or death was lower with a PCSK9 inhibitor (17.5% vs 25.4%): a 31% relative and 7.8% absolute risk reduction. LDL cholesterol fell by a mean of 54% (from 118 to 55 mg/dL). The data support early, intensive LDL lowering even before a first event.

Pharmacological blood-pressure lowering for the prevention of cardiovascular disease and death across the full spectrum of chronic kidney disease severity

an individual-participant data meta-analysis.

This individual-participant-data meta-analysis from the Blood Pressure Lowering Treatment Trialists' Collaboration (46 trials, 285,124 participants) examined blood-pressure lowering across all stages of chronic kidney disease (CKD). A 5 mmHg systolic reduction lowered major cardiovascular event risk similarly in people with (HR 0.91) and without CKD (HR 0.90), consistent across all CKD stages (including stages 4–5), blood-pressure thresholds (down to <120/70 mmHg) and proteinuria status. However, the relative benefit was attenuated in CKD with concomitant diabetes (HR 0.96), underscoring the need for adapted strategies in that high-risk subgroup.

Cerebral Amyloid Angiopathy.

Cerebral amyloid angiopathy (CAA) — deposition of beta-amyloid in the brain's small vessels — is a major cause of haemorrhagic stroke and contributes to cognitive decline and to complications of anti-amyloid immunotherapy. Diagnosis usually rests on MRI showing multiple (micro)bleeds or cortical/leptomeningeal blood products. For cardiovascular practice the key issue is the high recurrence risk: in patients with an indication for antithrombotic therapy, CAA demands a carefully individualised weighing of bleeding versus thrombotic risk. Research focuses on risk prediction, early markers and disease-modifying therapy.

Are clinical improvements in anxiety or depression associated with improvement in walking fitness following a cardiac rehabilitation programme?

Retrospective observational study on data from the UK National Audit of Cardiac Rehabilitation: 4,585 patients with acute coronary syndrome who underwent both a valid Incremental Shuttle Walk Test and the Hospital Anxiety and Depression Scale before and after cardiac rehabilitation between January 2021 and June 2024. Patients who achieved a minimum clinically important difference (MCID) for depression (>1.7-point HADS improvement) had 23% higher odds of also achieving the MCID for walking fitness (>70 m improvement; OR 1.23; 95% CI 1.01-1.49). Compared with home-based programmes, centre-based group programmes and hybrid programmes had higher odds of clinically meaningful improvement in walking fitness. Older age, female sex, physical inactivity, obesity, and longer waiting time were associated with lower likelihood of MCID improvement. The findings underscore the importance of integrating depression care within cardiac rehabilitation.

Clinical outcomes of conduction system pacing versus right ventricular pacing in patients with atrioventricular block

a systematic review and meta-analysis of randomised controlled trials

Systematic review and meta-analysis of randomised trials only — 5 RCTs with 985 patients with atrioventricular (AV) block — comparing conduction system pacing (CSP) with conventional right ventricular pacing (RVP). The composite endpoint significantly favoured CSP (HR 0.54; 95% CI 0.31-0.95; p=0.03), with markedly reduced risk of HF hospitalisation (RR 0.30; 95% CI 0.17-0.54; p<0.0001). No significant difference in all-cause mortality (RR 0.69; 95% CI 0.36-1.30; p=0.25). Secondary outcomes: significantly greater LVEF improvement (p=0.008) and shorter QRS duration (p=0.002) with CSP. In AV block, CSP therefore yields cardiac and clinical benefit over RVP — mainly through reduced HF hospitalisation and preservation of physiological activation. Mortality evidence remains uncertain. A practice shift toward CSP in pacemaker selection is supported by these data.

Multiorgan Physiological Deficits During Exercise Identify Clinical and Molecular Predisposition to Heart Failure With Preserved Ejection Fraction

Exercise unmasks the limited multi-organ reserve characteristic of heart failure with preserved ejection fraction (HFpEF). Using invasive cardiopulmonary exercise testing (iCPET), metabolite profiling and genomics, the investigators characterised seven exercise physiologic deficits in HFpEF patients: reduced exercise stroke volume and heart rate, a steep PCWP/cardiac-output slope, elevated pulmonary vascular resistance, pulmonary mechanical limitation, impaired peripheral oxygen extraction, and the obesity-related exaggerated metabolic cost of exercise. They mapped the distribution and the functional and prognostic significance of these deficits and linked them to molecular (metabolite and genetic) signatures — a step toward more targeted HFpEF phenotyping and risk assessment.

The Natural History of Massive Left Ventricular Hypertrophy in Pediatric Hypertrophic Cardiomyopathy

A Multiregistry Analysis

Massive left ventricular hypertrophy (LVH) is a risk factor for sudden cardiac death in children with hypertrophic cardiomyopathy (HCM), but its natural history is poorly understood. This analysis from two large international registries (SHaRe and IPHCC) compares children with HCM with and without massive LVH — defined as maximal wall thickness ≥30 mm or a z-score ≥+20 before age 18 — using serial wall-thickness measurements and composite outcomes for major ventricular arrhythmia events (sudden cardiac death, aborted sudden cardiac death or appropriate ICD therapy) and heart failure. The study characterises the course and risk profile of this severe phenotype to support risk stratification and treatment decisions such as ICD implantation.

Left ventricular thrombus in Takotsubo syndrome and ST-elevation myocardial infarction

Prospective cohort study at Sahlgrenska University Hospital in 314 patients with Takotsubo syndrome (TS, n=68), anterior STEMI (n=148), or non-anterior STEMI (n=98), with serial echocardiography on admission and days 1, 2, 3, 7, 14, and 30. Mean LVEF at admission: 39% in TS (lowest), 47% in anterior STEMI, and 53% in non-anterior STEMI. Despite the poorest LV function, no TS patient developed a left ventricular thrombus, while 20 of 246 STEMI patients (8.1%) did — almost exclusively anterior STEMI. All LV thrombi in anterior STEMI were detected within 7 days; the single non-anterior thrombus appeared at day 30. All patients received anticoagulation. Predictors: lower LVEF and higher troponin. The findings underscore pathophysiological differences between TS and STEMI and argue for distinct post-acute surveillance strategies.

Determining the Physiological Threshold for Angina (ORBITA-FIRE)

A Double-Blind, Randomized, Placebo-Controlled Study

Multicenter, double-blind, randomised, placebo-controlled study in 65 patients with stable angina and single-vessel coronary disease. After image-guided PCI, an in-stent balloon was incrementally inflated until angina occurred, verified against placebo inflation; FFR-angina and RFR-angina were recorded at symptom onset, also during low- and high-intensity exercise. Median pre-PCI FFR was 0.59 (IQR 0.46-0.70). Median FFR-angina at rest was 0.29 (IQR 0.23-0.35), during low-intensity exercise 0.38, and during high-intensity exercise 0.45. RFR-angina followed parallel values: 0.22 at rest, 0.26 at low, and 0.32 at high intensity. All thresholds were significantly lower than clinical ischaemia cut-offs (p<0.001). Lower FFR-angina thresholds were associated with greater baseline angina burden and greater symptom relief from PCI. The physiological angina threshold is therefore highly individualised, varies with cardiac workload, and lies well below universal cut-offs — arguing for symptom-led, personalised revascularisation strategy.

Angiotensin Receptor Neprilysin Inhibitor in Heart Failure with Preserved Ejection Fraction and Secondary Mitral Regurgitation

the PRAISE-MR Randomized Trial

Multicenter open-label randomised trial with blinded primary endpoint in 84 patients with symptomatic HFpEF and ≥moderate atrial functional mitral regurgitation (AFMR), randomised to sacubitril/valsartan (n=41) or standard of care (n=43). The primary endpoint was change in exercise mPAP/CO slope (mean pulmonary arterial pressure to cardiac output) measured via cardiopulmonary exercise testing with simultaneous echocardiography. At 6 months, mPAP/CO slope significantly improved with sacubitril/valsartan (adjusted between-group difference -0.93 mm Hg/L/min; 95% CI -1.80 to -0.07; p=0.035). Accompanying benefits: higher peak VO2 (+0.9 vs -0.6 mL/kg/min; p=0.002), higher KCCQ score (+10 vs +2 points; p=0.002), significantly lower NT-proBNP and LA volume (both p<0.001), and attenuation of the dynamic MR increase during exercise (p=0.020). Target dose was achieved in 60%; symptomatic hypotension was the main titration-limiting factor. A phenotype-specific benefit warranting confirmation in larger outcome trials.

Wrist-Measured Nighttime Home BP and Left Ventricular Hypertrophy

The WISDOM-HMOD Study

WISDOM-Night substudy in 1,218 patients with hypertension or heart failure (mean age 67.2 years; 53.9% men) using a wrist-type oscillometric home BP monitor (HEM9601T, Omron) to measure nighttime BP at 2:00, 3:00, and 4:00 am plus 4 hours after bedtime, alongside morning/evening BPs over 7 days. Mean nighttime SBP/DBP 110.5/63.5 mm Hg; 70.4% had well-controlled nighttime BP (<120/70). Echo-derived LV mass index: 90.1 g/m² in men, 80.3 g/m² in women. An increase in nighttime SBP was significantly associated with higher LV mass index, independent of office, morning, and evening home BP. Per 10 mm Hg increase in nighttime SBP, the OR for LVH was 1.36 (95% CI 1.15-1.60) overall, 1.54 in men, and 1.27 in women — sex-specific thresholds. Less sleep-disturbing wrist home monitors make nighttime BP monitoring accessible and clinically relevant.

Calcium Channel Blockade Versus Beta-Blockade for Hypertension in Heart Failure With Preserved Ejection Fraction

A Randomized Crossover Trial

Double-blind randomised crossover trial in 50 adults with HFpEF and hypertension, who received in random order 4 weeks of amlodipine 5-10 mg and 4 weeks of metoprolol succinate 100-200 mg (equipotent antihypertensive doses). Mean age 72 years, 68% women, 66% Black, baseline BP 144/78 mm Hg, 46% already on beta-blockers. Amlodipine produced significantly lower home systolic BP (-4 mm Hg; 95% CI -7 to -1; p=0.017), higher peak oxygen uptake during exercise (+1.2 mL/min/kg; p=0.008), higher physical activity (+0.1 MET-h/day; p=0.019), and lower NT-proBNP (-200 pg/mL; p<0.0001) than metoprolol. No difference in septal E/e', myocardial strain, or systemic vasodilatory reserve. Adverse events comparable. The results support dihydropyridine calcium channel blockers as a preferred alternative to beta-blockers for managing hypertension in HFpEF.

Evolocumab in Patients With Prior Percutaneous Coronary Intervention and No Prior MI

Results From the VESALIUS-CV Trial

Prespecified subgroup analysis of VESALIUS-CV in 3,627 patients (29.6% of the total study population) with prior PCI but no prior myocardial infarction or stroke, randomised to evolocumab or placebo (median follow-up 4.6 years). Median age 66 years, 30.7% women, median time since PCI 4 years. At 48 weeks, median LDL-C was 41.5 versus 107.0 mg/dL with evolocumab versus placebo. Evolocumab reduced 3-point MACE by 30% (5-year KM 7.0% vs 9.5%; HR 0.70; 95% CI 0.56-0.89; p=0.004), 4-point MACE by 18%, MI risk by 50% (3.0% vs 6.1%; HR 0.50; p<0.001), and urgent coronary revascularisation by 39%. The effect was apparent within 6 months. Numerically lower cardiovascular mortality (HR 0.66) and all-cause mortality (HR 0.76). The findings support intensive LDL-C lowering with evolocumab in stable patients with prior PCI even without prior MI — a substantial practical expansion of the indication.

Wrist-Measured Nighttime Home BP and Left Ventricular Hypertrophy

The WISDOM-HMOD Study

WISDOM-Night substudy in 1,218 patients with hypertension or heart failure (mean age 67.2 years; 53.9% men) using a wrist-type oscillometric home BP monitor (HEM9601T, Omron) to measure nighttime BP at 2:00, 3:00, and 4:00 am plus 4 hours after bedtime, alongside morning/evening BPs over 7 days. Mean nighttime SBP/DBP 110.5/63.5 mm Hg; 70.4% had well-controlled nighttime BP (<120/70). Echo-derived LV mass index: 90.1 g/m² in men, 80.3 g/m² in women. An increase in nighttime SBP was significantly associated with higher LV mass index, independent of office, morning, and evening home BP. Per 10 mm Hg increase in nighttime SBP, the OR for LVH was 1.36 (95% CI 1.15-1.60) overall, 1.54 in men, and 1.27 in women — sex-specific thresholds. Less sleep-disturbing wrist home monitors make nighttime BP monitoring accessible and clinically relevant.

Angiotensin Receptor Neprilysin Inhibitor in Heart Failure With Preserved Ejection Fraction and Secondary Mitral Regurgitation

The PRAISE-MR Randomized Trial

Multicenter open-label randomised trial with blinded primary endpoint in 84 patients with symptomatic HFpEF and ≥moderate atrial functional mitral regurgitation (AFMR), randomised to sacubitril/valsartan (n=41) or standard of care (n=43). The primary endpoint was change in exercise mPAP/CO slope (mean pulmonary arterial pressure to cardiac output) measured via cardiopulmonary exercise testing with simultaneous echocardiography. At 6 months, mPAP/CO slope significantly improved with sacubitril/valsartan (adjusted between-group difference -0.93 mm Hg/L/min; 95% CI -1.80 to -0.07; p=0.035). Accompanying benefits: higher peak VO2 (+0.9 vs -0.6 mL/kg/min; p=0.002), higher KCCQ score (+10 vs +2 points; p=0.002), significantly lower NT-proBNP and LA volume (both p<0.001), and attenuation of the dynamic MR increase during exercise (p=0.020). Target dose was achieved in 60%; symptomatic hypotension was the main titration-limiting factor. A phenotype-specific benefit warranting confirmation in larger outcome trials.

Determining the Physiological Threshold for Angina (ORBITA-FIRE)

A Double-Blind, Randomized, Placebo-Controlled Study

Multicenter, double-blind, randomised, placebo-controlled study in 65 patients with stable angina and single-vessel coronary disease. After image-guided PCI, an in-stent balloon was incrementally inflated until angina occurred, verified against placebo inflation; FFR-angina and RFR-angina were recorded at symptom onset, also during low- and high-intensity exercise. Median pre-PCI FFR was 0.59 (IQR 0.46-0.70). Median FFR-angina at rest was 0.29 (IQR 0.23-0.35), during low-intensity exercise 0.38, and during high-intensity exercise 0.45. RFR-angina followed parallel values: 0.22 at rest, 0.26 at low, and 0.32 at high intensity. All thresholds were significantly lower than clinical ischaemia cut-offs (p<0.001). Lower FFR-angina thresholds were associated with greater baseline angina burden and greater symptom relief from PCI. The physiological angina threshold is therefore highly individualised, varies with cardiac workload, and lies well below universal cut-offs — arguing for symptom-led, personalised revascularisation strategy.

Diastolic dysfunction is equally common in pre-diabetes and diabetes and associated with concomitant cardiometabolic risk factors

Cross-sectional study within the Swedish CArdioPulmonary bioImage Study (SCAPIS) in 3,840 men and women aged 50-64 years with transthoracic echocardiography, anthropometry, blood pressure, biochemistry, and coronary CT calcium scoring. Normoglycaemia 82%, pre-diabetes 12%, diabetes 6%. Diastolic dysfunction was significantly more common in pre-diabetes (30%) and diabetes (33%) than in normoglycaemia (21%); prevalence was therefore equivalent between pre-diabetes and diabetes. In dysglycaemic individuals, diastolic dysfunction was associated with hypertension and more severe coronary atherosclerosis. In multivariable analysis, waist circumference (OR 1.034) and high CAC score (OR 2.90) were independent predictors — even after excluding ischaemic heart disease. In individuals without coronary atherosclerosis and hypertension, systolic blood pressure remained the only independent predictor. The findings challenge the concept of an 'isolated diabetic cardiomyopathy' and argue for early, integrated cardiometabolic risk management to prevent HFpEF.

Evolocumab in Patients With Prior Percutaneous Coronary Intervention and No Prior MI

Results From the VESALIUS-CV Trial

Prespecified subgroup analysis of VESALIUS-CV in 3,627 patients (29.6% of the total study population) with prior PCI but no prior myocardial infarction or stroke, randomised to evolocumab or placebo (median follow-up 4.6 years). Median age 66 years, 30.7% women, median time since PCI 4 years. At 48 weeks, median LDL-C was 41.5 versus 107.0 mg/dL with evolocumab versus placebo. Evolocumab reduced 3-point MACE by 30% (5-year KM 7.0% vs 9.5%; HR 0.70; 95% CI 0.56-0.89; p=0.004), 4-point MACE by 18%, MI risk by 50% (3.0% vs 6.1%; HR 0.50; p<0.001), and urgent coronary revascularisation by 39%. The effect was apparent within 6 months. Numerically lower cardiovascular mortality (HR 0.66) and all-cause mortality (HR 0.76). The findings support intensive LDL-C lowering with evolocumab in stable patients with prior PCI even without prior MI — a substantial practical expansion of the indication.

Calcium Channel Blockade Versus β-Blockade for Hypertension in Heart Failure With Preserved Ejection Fraction

A Randomized Crossover Trial

Double-blind randomised crossover trial in 50 adults with HFpEF and hypertension, who received in random order 4 weeks of amlodipine 5-10 mg and 4 weeks of metoprolol succinate 100-200 mg (equipotent antihypertensive doses). Mean age 72 years, 68% women, 66% Black, baseline BP 144/78 mm Hg, 46% already on beta-blockers. Amlodipine produced significantly lower home systolic BP (-4 mm Hg; 95% CI -7 to -1; p=0.017), higher peak oxygen uptake during exercise (+1.2 mL/min/kg; p=0.008), higher physical activity (+0.1 MET-h/day; p=0.019), and lower NT-proBNP (-200 pg/mL; p<0.0001) than metoprolol. No difference in septal E/e', myocardial strain, or systemic vasodilatory reserve. Adverse events comparable. The results support dihydropyridine calcium channel blockers as a preferred alternative to beta-blockers for managing hypertension in HFpEF.

Dietary Intakes of Plant and Animal Nitrate and 5-Year Blood Pressure Changes

Cohort study in 2,942 Chinese adults analysing plant- versus animal-sourced nitrate intake via a validated food frequency questionnaire in relation to 5-year blood pressure changes and arterial stiffness (brachial-ankle pulse wave velocity). Higher plant nitrate intake was associated with greater 5-year SBP decline (β -3.51; 95% CI -5.89 to -1.13) and lower arterial stiffness (OR 0.59; 95% CI 0.35-0.98). Higher animal nitrate intake was conversely associated with DBP increase (β +1.95; 95% CI 0.54-3.37). In 2×2 analyses, plant nitrate + polyphenols or vitamin C gave the strongest BP decline, while animal nitrate + heme iron gave the strongest DBP rise. The BP effect of nitrate therefore depends strongly on the dietary context — an argument for actively promoting plant nitrate sources (green vegetables, beetroot) over animal sources (processed meat).

Dietary Intakes of Plant and Animal Nitrate and 5-Year Blood Pressure Changes

Cohort study in 2,942 Chinese adults analysing plant- versus animal-sourced nitrate intake via a validated food frequency questionnaire in relation to 5-year blood pressure changes and arterial stiffness (brachial-ankle pulse wave velocity). Higher plant nitrate intake was associated with greater 5-year SBP decline (β -3.51; 95% CI -5.89 to -1.13) and lower arterial stiffness (OR 0.59; 95% CI 0.35-0.98). Higher animal nitrate intake was conversely associated with DBP increase (β +1.95; 95% CI 0.54-3.37). In 2×2 analyses, plant nitrate + polyphenols or vitamin C gave the strongest BP decline, while animal nitrate + heme iron gave the strongest DBP rise. The BP effect of nitrate therefore depends strongly on the dietary context — an argument for actively promoting plant nitrate sources (green vegetables, beetroot) over animal sources (processed meat).

Infective endocarditis after transcatheter aortic valve implantation

risk factors and mortality impact in a case-control study

Case-control study at Haukeland University Hospital (Norway, 2012-2023) comparing 71 patients with TAVI-related infective endocarditis (TAVI-IE) to 213 age- and sex-matched controls without IE (1:3 ratio). Incidence was 1.2% per patient-year; median time from TAVI to infection was 13 months (IQR 4-29). Diabetes mellitus was the only independent predictor of TAVI-IE in multivariable competing-risk analysis (SHR 2.08; 95% CI 1.19-3.65). Obesity (27% vs 15%) and balloon-expandable valve use (28% vs 13%) were more frequent in IE patients. Enterococcus faecalis was the most common pathogen (30%). TAVI-IE was associated with approximately twofold higher all-cause mortality (aHR 2.13; 95% CI 1.48-3.07), with the highest risk in early infections. The findings can guide targeted monitoring and prevention in high-risk patients.

Adolescent Cardiorespiratory Fitness and the Trade-Off Between Atrial Fibrillation Risk and Cardiovascular Benefits

A Nationwide Sibling-Controlled Cohort Study

Nationwide Swedish cohort with sibling-controlled analysis of 1,124,049 men (mean age 18.3 years) who underwent mandatory military fitness testing between 1972 and 1995, followed until December 2023. 45,179 (4.0%) developed atrial fibrillation and 96,404 (8.6%) had non-AF cardiovascular disease (median events around age 55 years). In population-wide analysis, the fittest men (highest decile) had a small excess of AF in early adulthood but greater reductions in non-AF CVD from age 45. In full-sibling comparison (controlling for shared familial factors), the trade-off disappeared entirely: from age 35 the reduction in non-AF CVD was already larger (RD -0.11%) than the AF excess (RD +0.06%); at age 65, respectively -3.91% versus +2.30%. High youth fitness therefore confers no net cardiovascular disadvantage — supporting public-health efforts to improve youth fitness and reassuring about the safety of high fitness levels.

Adolescent Cardiorespiratory Fitness and the Trade-Off Between Atrial Fibrillation Risk and Cardiovascular Benefits

A Nationwide Sibling-Controlled Cohort Study

Nationwide Swedish cohort with sibling-controlled analysis of 1,124,049 men (mean age 18.3 years) who underwent mandatory military fitness testing between 1972 and 1995, followed until December 2023. 45,179 (4.0%) developed atrial fibrillation and 96,404 (8.6%) had non-AF cardiovascular disease (median events around age 55 years). In population-wide analysis, the fittest men (highest decile) had a small excess of AF in early adulthood but greater reductions in non-AF CVD from age 45. In full-sibling comparison (controlling for shared familial factors), the trade-off disappeared entirely: from age 35 the reduction in non-AF CVD was already larger (RD -0.11%) than the AF excess (RD +0.06%); at age 65, respectively -3.91% versus +2.30%. High youth fitness therefore confers no net cardiovascular disadvantage — supporting public-health efforts to improve youth fitness and reassuring about the safety of high fitness levels.

Physical fitness after myocardial infarction compared with clinical reference values

a SWEDEHEART registry study

Registry study from the Swedish SWEDEHEART post-MI register (2016-2019) in 15,105 patients with first-time myocardial infarction (mean age 62.5 years; 78.4% male) who underwent physiotherapist-led assessments of exercise capacity (symptom-limited cycle ergometry) and muscular endurance (unilateral heel-rise test) at the start of cardiac rehabilitation. Results were compared with Swedish age- and sex-stratified reference values (Kalmar dataset). Mean exercise capacity was only 64.7% of predicted in men and 68.4% in women; muscular endurance 78.4% in men and 61.7% in women. Women showed a steeper age-related decline in heel-rise performance. The results underscore the importance of systematic baseline assessment and tailored rehabilitation targeting both exercise capacity and muscle strength.

Risk factors for multimorbidity of cardiovascular diseases in the prospective Million Women Study

Prospective cohort within the UK Million Women Study: 1.3 million women aged 50-64 recruited in 1996-2001, with baseline data on demographics, BMI, smoking, alcohol, physical activity, and treatment for hypertension, diabetes, and hypercholesterolaemia. Through linked hospital and death records, 19 cardiovascular disease subtypes were tracked. Cardiovascular multimorbidity (CVM, ≥2 diagnoses) and complex CVM (≥4 diagnoses) were analysed. Obesity, smoking, and treated diabetes or hypertension were each independently associated with 2-3× higher CVM risk; severe obesity, heavy smoking, and diabetes with 3-4× higher complex-CVM risk. Strongest associations: severe obesity with fivefold risk of atrial fibrillation + heart failure together, and diabetes with fivefold risk of ischaemic heart disease + heart failure together. Alcohol and physical activity showed weak associations. Targeted risk-factor management is particularly important in women to prevent CV multimorbidity.

Estimating 5-year absolute risk of cardiovascular disease using routinely collected electronic medical records from Australian general practices

Study using routinely collected electronic medical records (EMRs) from 680 Australian general practices (Lumos programme, linked to hospital and death records) in 850,216 patients aged 30-74 years without prior CVD. Over a mean follow-up of 4.9 years, 33,578 cardiovascular events occurred. Sex-specific Cox models with 28 predictors achieved Harrell's C 0.803 (95% CI 0.801-0.804) in females and 0.772 (95% CI 0.770-0.773) in males; simpler LASSO models with 12-15 predictors performed similarly. Models were well calibrated across age, socioeconomic strata, and smoking status, with consistent discrimination across 10 regional Primary Health Networks. Net reclassification improvement up to 0.185 versus existing AusCVDRisk variables. EMR-based models are suitable for automated integration into primary-care software for real-time CVD risk assessment — an important scalability step for primary prevention.

Natural history of asymptomatic moderate or severe aortic regurgitation

a systematic review and meta-analysis

Systematic review and meta-analysis of 27 cohort studies (4,720 patients; mean age 49 years; median follow-up 3.9 years) on the natural history of asymptomatic moderate or severe aortic regurgitation (AR). Pooled incidence per 100 person-years: all-cause mortality 1.75 (95% CI 1.27-2.41), cardiac death 1.29, sudden death 0.29, new symptoms 4.30, and aortic valve replacement/repair (AVR) 7.01. Asymptomatic LV dysfunction occurred at only 0.9 per 100 person-years. Mortality rates were more than double those of the general population irrespective of age — 2.45 per 100 person-years in cohorts ≥50 years versus 0.59 in younger cohorts. Early AVR was associated with lower mortality (pooled HR 0.33; 95% CI 0.30-0.37). The findings contradict the historical view of AR as a 'benign' valvular lesion and argue for earlier intervention guided by more sensitive markers of LV damage.

Real-World Incidence of Cancer Therapy-Related Cardiac Dysfunction in a Large, Diverse, and Contemporary Cohort.

Retrospective cohort study within Kaiser Permanente Northern California: 26,646 adults diagnosed with malignant tumours between 2012-2022 who received anthracyclines, HER2 inhibitors, immune checkpoint inhibitors (ICIs), or tyrosine kinase inhibitors (TKIs). Mean age 62 years, 64% women. Cancer therapy-related cardiac dysfunction (CTRCD) — defined as >10% LVEF decline to <53% or incident heart failure — occurred in 8.4% (95% CI 7.7-9.1) cumulative. Highest incidence with HER2 inhibitors (10.7%), lowest with ICIs (5.2%) (p<0.001). Nearly half of all events occurred within the first year. The cohort supports early risk prediction models and targeted cardiology surveillance during oncologic therapy to reduce downstream HF risk — a key message for cardio-oncology practice.

Pulsed Field Ablation Versus Sham to Treat Atrial Fibrillation

The PFA-SHAM Randomized Clinical Trial

Prospective, sham-controlled, single-blind randomised trial in 60 patients with highly symptomatic atrial fibrillation (AFEQT score <50), assigned 1:1 to pulsed field ablation (PFA) or a sham procedure. All participants received implantable rhythm monitors for continuous rhythm monitoring. At 6 months: AF recurrence occurred in 6.7% (PFA) versus 83.3% (sham); posterior HR 19.6 (95% Bayesian credible interval 6.7-76.9; posterior superiority probability >0.99). Quality of life (AFEQT) improved +43.9 points with PFA versus +11.3 with sham (difference +32.6 points). AF burden was significantly lower with PFA (median 0% vs 0.43%). Anxiety/depression score (HADS) improved -4 points with PFA versus -0.5 with sham. This first sham-controlled PFA trial excludes a placebo effect and confirms PFA as robustly effective in symptomatic AF — both objectively (rhythm) and subjectively (quality of life, psychological distress).

Direct Oral Anticoagulants, COX-2-Selective NSAIDs, and Gastrointestinal Bleeding in Atrial Fibrillation.

Multinational cohort study (UK EHR + Quebec claims, 2011-2020) in 30,240 patients with nonvalvular atrial fibrillation initiating concomitant DOAC and NSAID (37,833 episodes; 45.2% COX-2-selective, 54.8% nonselective). Mean age 72.1 years, 56.7% male. Pooled weighted analysis with inverse-probability-of-treatment weighting showed that COX-2-selective NSAIDs combined with DOACs were associated with fewer gastrointestinal bleeds (HR 0.63; 95% CI 0.46-0.87; I²=56%) and fewer non-GI bleeds (HR 0.54; 95% CI 0.40-0.74; I²=0%) versus nonselective NSAIDs. The effect was stronger in women (HR 0.50 for GI bleeding) than in men (HR 0.85). No major effect modification by age, order of initiation, baseline bleeding risk, or specific DOAC. COX-2-selective NSAIDs thus retain their GI-protective benefit during DOAC therapy; future research should clarify the relationship with stroke risk.

Diet-Gut Microbiota Interaction Index and Heart Failure Risk in Diabetes and Prediabetes

Evidence from NHANES 2007-2018.

Cross-sectional analysis of NHANES 2007-2018 data in 15,219 US adults with diabetes or prediabetes. The Dietary Index for Gut Microbiota (DI-GM) was calculated from two 24-hour dietary recalls covering 14 food groups linked to gut microbiota. Higher DI-GM scores were independently associated with lower heart failure risk (aOR 0.93 per point; 95% CI 0.89-0.98; p=0.005). Compared with scores 0-3, DI-GM ≥6 was associated with 27% lower HF risk (OR 0.73; 95% CI 0.58-0.92; p=0.007). The inverse association was stronger in prediabetes (OR 0.89 per point; p=0.004) but not significant in diabetes. Microbiota-related dietary patterns may thus play a role in HF prevention in metabolically vulnerable populations.

Coronary Embolism in Atrial Fibrillation

A Distinct High-Risk Phenotype With Residual Thromboembolic Risk Despite Anticoagulation.

Retrospective cohort study (China, 2014-2023, n=4,777 with acute myocardial infarction) in which coronary embolism (CE) was diagnosed via a 3-step validation process (Shibata criteria, angiographic core lab, final adjudication). Patients were grouped: CE with AF (n=78), non-CE AMI with AF (n=205), and non-CE AMI without AF (n=3,937), with propensity-score overlap weighting. CE accounted for 1.6% of all AMIs and 14.7-27.6% of AF-related AMIs. Compared with non-CE AMI without AF, CE+AF patients had significantly higher all-cause mortality (aHR 1.77; 95% CI 1.15-2.71) and ischaemic stroke (aHR 4.45; 95% CI 2.34-8.45), despite 79.2% receiving therapeutic anticoagulation. CE in AF is therefore an underrecognised high-risk phenotype with residual thromboembolic risk. The authors advocate multimodal imaging, embolism-targeted reperfusion, and optimisation of antithrombotic therapy including standard-dose DOACs.

Out-of-hours primary care management for patients with heart failure.

Dutch observational study of out-of-hours primary care (OHS-PC) contacts for acute shortness of breath (Sep 2020-Aug 2021). Of 1,833 calls, 102 (5.1%) involved patients in whom heart failure was deemed the cause (mean age 79.6 years, 53% women). 10 (9.8%) were referred directly to the emergency department; of the remaining 92, 60.8% were assessed by home visit, 14.7% at the clinic, and 14.7% by telephone advice. Subsequently 44.6% were referred to the ED and 42.4% received loop diuretics at home (new or up-titrated). Of the 51 ED-referred patients, 82.4% were admitted. The 6-month all-cause mortality was 32.3%. The findings underscore that heart failure patients in out-of-hours primary care are a high-risk subgroup with substantial heterogeneity in care pathway — relevant for triage and long-term outcomes in primary-care acute services.

Blinded withdrawal of randomized treatment with low-dose digoxin or placebo in patients with heart failure

the DECISION trial.

Prespecified analysis of the DECISION trial: 1,001 heart failure patients on contemporary guideline therapy were randomised to low-dose digoxin or placebo, with a median treatment of 36.5 months. At study end, 587 patients on active treatment (288 digoxin, 299 placebo) underwent blinded withdrawal with 6-week follow-up. During the 100 days before withdrawal, cardiovascular death/HF event rates were similar (5.7 vs 6.5 events per 100 patient-years). After withdrawal, the rate rose sharply in the digoxin arm but not in the placebo arm (42.8 vs 5.9 per 100 patient-years; time-by-treatment interaction p=0.036). 14 events occurred in the digoxin withdrawal arm (12 hospitalisations, 2 urgent HF visits) versus 2 in the placebo withdrawal arm (RR 7.37; 95% CI 1.56-34.88; p=0.012). Withdrawal was accompanied by higher heart rate, lower systolic BP, and rising NT-proBNP. Conclusion: caution is warranted when stopping long-standing digoxin in HF with (mildly) reduced ejection fraction.

1-Year Real-World Outcomes With the Amulet Occluder From the EMERGE LAA Postapproval Study.

Postapproval registry (EMERGE LAA) of the first 12,180 patients with attempted Amulet occluder implantation for left atrial appendage occlusion (LAAO) in nonvalvular atrial fibrillation, captured in the US NCDR LAAO Registry between August 2021 and December 2023. Implantation success was 96.0% — 88.9% in patients with prior failed LAAO attempt. Clinically relevant closure (peridevice leak ≤3 mm) at day 45 was 97.2%. The composite safety endpoint (death, ischaemic stroke, embolism, device-/procedure-related events) occurred in 0.9%. Major adverse events at day 45 decreased with operator experience (8.4% at <10 cases to 5.8% at ≥30; p<0.001). At 1 year: 1.6% all stroke, 6.3% major bleeding, 2.9% CV/unknown-cause death, 7.9% all-cause death. The real-world data confirm safety and effectiveness of the Amulet occluder and highlight the impact of the learning curve on procedural outcomes.

Outcomes after a first acute myocardial infarction in patients with or without congenital heart disease.

Nationwide case-control study (2000-2022) of 214 adults with congenital heart disease (ACHD) and their first acute myocardial infarction, matched to 2,092 controls without ACHD on age, sex, hypertension, diabetes, hyperlipidaemia, and previous PCI/CABG. ACHD patients were younger at first infarction (58 vs 70 years). Over a mean follow-up of 6.5 (ACHD) and 7.3 years (controls), no difference emerged in mortality or recurrent MI at 1 year. At 10 years, mortality appeared higher in ACHD (HR 1.4; 95% CI 1.0-1.9) but lost significance after adjustment. The findings suggest ACHD patients have survival similar to the general population after MI. Since they share the same cardiovascular risk factors, healthy lifestyle and proactive risk management remain essential to prevent acquired heart disease in this growing population.

One-year multicenter prospective real-world study of vericiguat effectiveness and safety in Spain.

Prospective multicenter registry (VERISEC) of 835 consecutive patients with HFrEF after recent decompensation initiating vericiguat at 41 Spanish centres (mean age 71.3 years, 78.9% male). Baseline therapy was highly optimised: 91.5% SGLT2i, 90.7% beta-blockers, 85.4% RAAS inhibitors, 79.8% MRAs; quadruple therapy was 61.7-63.0% throughout follow-up. At 1 year, NT-proBNP fell from 3,532 to 2,292 pg/mL (p<0.001), LVEF rose from 30.3% to 35.4% (p<0.001), and NYHA class improved. HF decompensations requiring IV diuretics halved (1.34 → 0.65/year); non-HF cardiovascular hospitalisations fell from 0.98 to 0.39/year. Vericiguat was discontinued in 13.4%, mostly for symptomatic hypotension (49.4%); higher baseline NT-proBNP predicted discontinuation (OR 1.06 per 1,000 pg/mL). The real-world data confirm clinical utility and safety of vericiguat on top of quadruple therapy.

Drug targets for lipid modification and risk of type 2 diabetes

a cis-Mendelian randomization study.

Cis-Mendelian randomisation study using individual-level data from UK Biobank, Lifelines, and publicly available GWAS sources, examining 13 lipid-related drug targets (including ACLY, ANGPTL3/4, APOB, APOC3, CETP, HMGCR, LDLR, LIPG, LPA, MTTP, NPC1L1, and PCSK9). Lipid modification via HMGCR (statins) was predicted to reduce CAD risk but increase type 2 diabetes risk — a known statin side-effect. Modification via APOC3, LDLR, LPA, MTTP, NPC1L1, and PCSK9 reduced CAD risk without changing T2D risk. ANGPTL4 and CETP reduced risk of both CAD and T2D. For ACLY, ANGPTL3, APOB, and LIPG, no genetic evidence was found for either CAD or T2D effects. The findings suggest substantial variation in diabetes risk between lipid-lowering classes and may guide future drug development and individual therapy decisions.

Lipid-related cardiovascular risk beyond low-density lipoprotein cholesterol.

Heart review of lipid-related cardiovascular risk beyond LDL cholesterol. While LDL lowering has been the dominant target for decades, mechanistic, observational, and genetic studies support a causal role for remnant particles and lipoprotein(a) in ASCVD development. Multiple new drugs targeting these are now in development with RCT results expected. Lipoprotein(a) is largely genetically determined; remnant cholesterol correlates strongly with overeating, obesity, and diabetes. The global obesity epidemic is driving an increase in metabolic dyslipidaemias and related ASCVD risk. The era of LDL-only risk management is over — targeted approaches to metabolically dysregulated and genetically driven lipid fractions are becoming increasingly important.

Intracoronary imaging for left main percutaneous coronary intervention

a clinical consensus statement of the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC and the European Bifurcation Club (EBC).

Joint clinical consensus statement from EAPCI and the European Bifurcation Club (EBC) on intracoronary imaging for left main percutaneous coronary intervention. The document underpins recent American and European guideline recommendations to use intravascular ultrasound (IVUS) or optical coherence tomography (OCT) for planning, guidance, and optimisation of left main bifurcation PCI in both chronic and acute coronary syndromes. The authors emphasise that benefit will only be realised when the interventional community routinely deploys intracoronary imaging for these complex high-risk lesions. The document provides practical guidance to maximise the benefit of IVUS and OCT in left main bifurcation disease.

Laroprovstat, the First Oral Small-Molecule PCSK9 Inhibitor for the Treatment of Hypercholesterolemia

Results From a Randomized, Single-Blind, Placebo-Controlled Phase 1 Trial in Treatment-Naive Patients.

Phase 1 randomised, single-blind, placebo-controlled trial of laroprovstat (AZD0780), the first oral small-molecule PCSK9 inhibitor. Unlike injectable PCSK9 antibodies, laroprovstat does not block the PCSK9-LDLR interaction but stabilises the PCSK9 C-terminal domain, preventing lysosomal degradation of the LDL receptor. In healthy participants with LDL-C ≥70 and ≤190 mg/dL, pharmacokinetics were dose-proportional and suitable for once-daily dosing (half-life ~40 hours), with no food interaction. After a 3-week run-in with rosuvastatin 20 mg, laroprovstat 1 mg reduced LDL by 29% and 30 mg by 51% versus baseline. Combined rosuvastatin + laroprovstat resulted in total LDL reductions of ~70% and ~80%. Safety was favourable with no concerning signals. The results support further development as the first oral PCSK9 inhibitor.

Homozygous familial hypercholesterolaemia

insights from the Global HICC Registry.

Data from the Global HoFH International Clinical Collaborators (HICC) registry, which has now included over 950 patients with homozygous familial hypercholesterolaemia (HoFH) from 45 countries. HoFH is characterised by extremely elevated LDL cholesterol from birth and very high risk of premature atherosclerotic CVD. Median age at diagnosis was 12 years (IQR 5.5-27.0), with untreated LDL cholesterol at median 14.7 mmol/L. At diagnosis 9% already had ASCVD or (supra)aortic valve disease; despite widespread lipid-lowering therapy, only 4% reached guideline LDL goals. Early initiation of lipoprotein apheresis was associated with greater LDL reductions and delayed ASCVD onset. Median age at death is just 37 years [20-50]. No sex differences emerged at diagnosis or in treatment, and the usual sex gap in CVD onset is absent. Global disparities in genetic screening and access to therapy are profound, with earlier events in low-income countries.

Age-Dependent Association between Heart Failure and Stroke Risk in Atrial Fibrillation

A Nationwide Cohort Study.

Nationwide Finnish retrospective cohort study (FinACAF) of 229,565 patients with new-onset atrial fibrillation (AF) between 2007 and 2018. Prevalence of heart failure was much higher in older than younger patients (38.7% vs 4.3%). The relative association between heart failure and ischaemic stroke was age-dependent: in patients <60 years the incidence rate ratio was ≥2.0, falling to ≈1.0 in the oldest group (p<0.001 for interaction). The adjusted absolute event-rate difference remained stable at ≈1 event per 100 patient-years across all age categories. The findings argue for extra weight on heart failure when deciding on oral anticoagulation in younger AF patients — co-existing HF is prognostically more important in this group than in older patients.

Association of Dietary Patterns and Genetic Risk With Cardiovascular Disease in UK Biobank Cancer Survivors.

Prospective cohort study in UK Biobank of 10,414 cancer survivors free of prior CVD who had completed ≥2 dietary recalls (mean age 59.5 years, 37% men). Over a median follow-up of 13.1 years, 1,331 incident CV events occurred. Higher adherence to four healthy dietary patterns reduced CV risk (highest vs lowest tertile): alternate Mediterranean diet HR 0.83, Alternative Healthy Eating Index 2010 HR 0.76, Dietary Approaches to Stop Hypertension HR 0.82, EAT-Lancet HR 0.85. Effects were consistent for ischaemic heart disease (HR 0.77-0.85); AHEI-2010, DASH, and EAT-Lancet also reduced heart failure risk (HR 0.74-0.88); AHEI-2010 and EAT-Lancet also reduced stroke risk. There was no interaction with genetic CVD risk. Healthy eating thus benefits cancer survivors regardless of genetic predisposition — a growing high-risk population.

Clinical Effectiveness of Sodium-Glucose Cotransporter-2 Inhibitors Among Older Patients Hospitalized for Heart Failure With Reduced Ejection Fraction.

Analysis of Medicare data from Get with the Guidelines-Heart Failure: 8,847 patients aged ≥65 years hospitalised for HFrEF between July 2021 and June 2023, eligible for SGLT2 inhibitors but not yet receiving them (median age 77 years, 40% women, median LVEF 28%). 16.5% (n=1,464) initiated an SGLT2 inhibitor at discharge. After overlap weighting via propensity score, SGLT2i initiation was independently associated with lower 12-month all-cause mortality (aHR 0.76; 95% CI 0.67-0.86), all-cause readmission (aHR 0.89), and HF readmission (aHR 0.84). Findings were consistent across age, sex, race/ethnicity, diabetes status, CKD status, and LVEF. Early in-hospital initiation of SGLT2 inhibitors thus improves prognosis in older HFrEF patients in routine practice — a population previously underrepresented in RCTs.

Comparative Effectiveness of Individual Sodium Glucose Transporter 2 Inhibitors on Cardiovascular Outcomes in Type 2 Diabetes With Moderate Cardiovascular Risk

Emulation of a Target Trial.

Target trial emulation on US claims data (commercial + Medicare) of adults with type 2 diabetes and moderate cardiovascular risk who started canagliflozin (n=42,877), dapagliflozin (n=17,871), or empagliflozin (n=7,648) between 2015 and 2020. In the weighted cohort (n=137,232; mean age 65.7 years, 81.9% on metformin), MACE risk was slightly lower with empagliflozin versus canagliflozin (HR 0.92; 95% CI 0.87-0.97), driven by reduced all-cause mortality (HR 0.86). Empagliflozin versus dapagliflozin and dapagliflozin versus canagliflozin did not differ. No differences in hyperglycaemic or hypoglycaemic crises between the three drugs. The three most commonly used SGLT2 inhibitors show comparable cardiovascular effectiveness; clinicians and health systems should prioritise enhancing access to this class rather than drug selection.

Cost-effectiveness and budget-impact analysis of tirzepatide in heart failure with preserved ejection fraction and obesity in the German health-care system.

Markov model of tirzepatide versus placebo (both on top of standard care) in the SUMMIT population (HFpEF + obesity) from the German payer perspective, with monthly cycles over 5 years and four KCCQ-defined health states plus death. Discounted per-patient costs: €5,827 (placebo) versus €31,052 (tirzepatide), with QALYs of 3.539 versus 3.638. Tirzepatide yielded 0.100 additional QALYs at incremental costs of €25,225, ICER €252,611/QALY — far above the €100,000/QALY threshold. Five-year budget impact: €1.9-6.2 billion under SUMMIT criteria and €3.8-12.6 billion under broad eligibility, depending on uptake (30/50/100%). Substantial price reduction would be needed for tirzepatide to be both cost-effective and affordable at population scale.

Effect of Different Types of Whole Dietary Pulses on Established Therapeutic Lipid Targets for Cardiovascular Risk Reduction

An Updated Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials.

Systematic review and dose-response meta-analysis of 38 randomised trials (52 comparisons, n=2,095) on the effect of whole dietary pulses on lipid targets. Median duration 6 weeks, median dose 130 g/day (0.5-0.67 cup). Pulses reduced LDL cholesterol by -0.14 mmol/L (95% CI -0.19 to -0.08), non-HDL cholesterol by -0.22 mmol/L, apoB by -0.08 g/L, and HDL by -0.03 mmol/L (the last clinically trivial). No effect on other lipids. Results were consistent across pulse types. For beans, a linear inverse relationship was demonstrated up to 1 cup/day for LDL (-0.25 mmol/L per 0.5 cup) and non-HDL (-0.45 mmol/L per 0.5 cup). GRADE certainty was moderate-to-high for most outcomes. Effects are small-to-moderate but clinically meaningful, supporting dietary guidelines on pulses as a lipid-lowering strategy.

European Society of Cardiology

cardiovascular disease statistics 2025.

Fifth biennial ESC Atlas report presenting cardiovascular disease statistics from more than 50 ESC member countries for 2024. CVD causes over 3 million deaths and 68 million disability-adjusted life years annually in the region, remaining the leading cause of death. Substantial variation exists by national income: middle-income countries show age-standardised mortality roughly twice that of high-income countries, with major disparities in workforce capacity and access to advanced interventions. The report informs the EU Safe Hearts Plan (adopted December 2025) and highlights new threats — particularly the obesity and diabetes epidemic — that risk reversing progress in CVD reduction. Ageing and socioeconomic inequality call for coordinated European policy to safeguard further progress.

Low-Density Lipoprotein Cholesterol Lowering With Inclisiran Plus Usual Care in Recent Acute Coronary Syndrome

VICTORION-INCEPTION, a Randomized, Controlled, Open-Label Trial.

Open-label phase 3b multicenter randomised trial in 400 patients ≤5 weeks after acute coronary syndrome with LDL-C ≥70 mg/dL (or non-HDL ≥100 mg/dL) on statin therapy or statin-intolerant. 1:1 randomisation to inclisiran 300 mg (days 0, 90, 270) plus usual care versus usual care alone, with 330 days of follow-up. At day 90, 74.6% of inclisiran patients reached LDL <70 mg/dL versus 26.6% with usual care (OR 10.84); for LDL <55 mg/dL it was 63.2% vs 8.5% (OR 26.58). At day 330 the gap persisted: 66.7% vs 28.1% for LDL <70 (OR 5.42; p<0.001) and 54.2% vs 13.6% for LDL <55. Mean LDL reduction from baseline was -46.9% greater with inclisiran. Adverse events were comparable between arms (58.6% vs 53.3%). The first inclisiran trial in recent ACS — early addition rapidly and durably achieves guideline LDL targets.

Mobile Health Unit Outreach to Socially Disadvantaged Urban Communities Detects Uncontrolled Cardiometabolic Risk Factors.

Cross-sectional analysis of the Wayne State University/Wayne Health mobile health unit program, which conducted screening at over 1,000 locations across metropolitan Detroit between July 2021 and September 2025. In voluntary adult participants: median BP 122/75 mm Hg, LDL cholesterol 103 mg/dL, HbA1c 5.7%. About half had elevated BP (48%; n=6,182/12,821) or LDL ≥100 mg/dL (54%; n=3,860/7,115); 16% had HbA1c ≥6.5%. Among 5,393 participants with all four measurements, only 4% had an ideal cardiometabolic risk profile (SBP <120, LDL <70, HbA1c <5.7%), while 70% had at least one uncontrolled risk factor. Older age predicted all four; Black race predicted uncontrolled BP; male sex predicted uncontrolled BP and HbA1c. Mobile units are a valuable tool for detection and targeted intervention in socioeconomically disadvantaged populations.

Optimal Exercise Modalities and Dosages for Blood Pressure Reduction in Adults With Prehypertension and Established Hypertension

A Network Meta-Analysis and Dose-Response Relationship Study.

Bayesian network meta-analysis of 105 randomised trials examining different exercise modalities and doses on blood pressure in prehypertension and established hypertension. Combined training (strength + aerobic) reduced systolic blood pressure by -12.05 mm Hg (95% CrI -15.08 to -9.05) and diastolic by -6.20 mm Hg; high-intensity interval training reduced systolic by -10.97 mm Hg and diastolic by -6.42 mm Hg. Yoga and tai chi had moderate effects; aerobic, isometric, and resistance training were relatively weaker as single modalities. Dose-response was non-linear and U-shaped, with greatest benefit at ~830 metabolic-equivalent minutes per week (optimal dose varying by modality). Conclusion: all modalities lower BP; combined training and HIIT are most effective, with diminishing returns beyond ~830 MET-min/week.

Primary Results of the SALAMANDER Registry

A Multicenter Observational Cohort Study.

Prospective multicenter observational cohort of 1,660 patients with non-valvular atrial fibrillation undergoing stand-alone left atrial appendage occlusion (LAAO) at 16 European centres between 2010 and 2024. Median age 76 years (IQR 70-81); 38% women; median CHA2DS2-VASc 4. Indication was significant bleeding in 83.7% — most often on DOAC (68.8%) and less often VKAs (24.9%); main bleeding sites were lower (27.9%) and upper (21.7%) GI tract, with 17.4% history of haemorrhagic stroke. Technical success 95.5% (limited mainly by residual leak 2.2% and tamponade 1.4%); procedural success 90.5% (vascular complications 3.7%, periprocedural death 1.1%). Results were comparable across devices. Virtually all patients received dual antiplatelet therapy post-procedure.

Preservative food additives, hypertension, and cardiovascular diseases

the NutriNet-Santé study.

Prospective French cohort study (NutriNet-Santé, 2009-2024) in 112,395 participants (78.7% women; mean age 42.8 years; median follow-up 7.9 years). Dietary intake was assessed via repeated 24-hour dietary records (up to 96 per participant); exposure to food additives was analysed using multiple composition databases and laboratory assays. Total non-antioxidant preservatives were associated with increased incident hypertension (n=5,544; HR highest vs lowest consumers 1.29; 95% CI 1.20-1.39) and cardiovascular disease (n=2,450; HR 1.16). Antioxidant preservatives were linked only to hypertension (HR 1.22). Of 17 individually examined additives (consumed by ≥10%), eight were associated with hypertension and one with CVD after multiple-testing correction. If confirmed experimentally, the findings call for re-evaluation of regulations on industrial food additives.

Body Composition Changes in Patients on GLP-1 Receptor Agonists Undergoing an Intensive Cardiac Rehabilitation Program.

Retrospective cohort of 468 patients enrolled in a structured Pritikin intensive cardiac rehabilitation program (UC San Diego, 2017-2024), 67 of whom were taking GLP-1 receptor agonists for a median of 231 days. Body composition was assessed by bioelectrical impedance at baseline and program completion. GLP-1 RA users had higher baseline BMI and body fat but similar skeletal muscle mass (SMM). After adjustment for age, sex, BMI, diabetes, and fitness, there was no significant difference in percent change in SMM (β 0.62%; 95% CI -0.62 to 1.86; p=0.33) or fat mass (p=0.20) between users and non-users. Both groups improved METs significantly. The findings counter — in this setting — the concern that GLP-1 therapy drives clinically relevant sarcopenia and support combining it with structured exercise.

Autosomal Dominant Alport syndrome.

JASN review of autosomal dominant (AD) Alport syndrome, caused by heterozygous pathogenic variants in COL4A3 or COL4A4. With ~1% population prevalence, it is the most common monogenic kidney disease — characterised by persistent glomerular haematuria, thinned glomerular basement membrane, and family history of kidney disease, without the hearing and ocular abnormalities of X-linked Alport. Penetrance is incomplete (only two-thirds of variant carriers have haematuria). Missense mutations with glycine substitutions confer proteinuria more often. Genetic testing distinguishes AD from X-linked Alport (the latter has higher kidney-failure risk). Recommended: monitoring of albuminuria and treatment with ACE inhibitors and, if needed, SGLT2 inhibitors from onset; genetic testing for all first-degree relatives regardless of haematuria status.

Projected reduction in major adverse cardiovascular events among high-risk U.S. adults with type 2 diabetes eligible for oral semaglutide

a SOUL trial-based analysis using NHANES (1988-2018) cycles.

Population-level modeling study applying SOUL trial eligibility criteria to NHANES data of US adults with type 2 diabetes. An estimated 6.1 million Americans met eligibility for oral semaglutide. Without treatment, 847,598 major adverse cardiovascular events (MACE) were projected over 4.5 years; with treatment, 728,934 — a potential prevention of 118,664 events (14% relative reduction; NNT 55). At 50% uptake and 15.5% discontinuation (as in SOUL), this translates to roughly 59,000 MACE prevented, including 14,000 CV deaths, 41,000 non-fatal MIs, and 12,000 non-fatal strokes. The findings support oral semaglutide as a scalable cardiometabolic intervention and argue for system-level strategies to enhance access and uptake.

Lipid clinics worldwide

harmonization and guidance on how to optimally organize and fund. European Atherosclerosis Society consensus statement across 55 countries and more than 500 lipid clinics

Through its Lipid Clinic Network, the European Atherosclerosis Society (EAS) presents the first worldwide consensus on lipid clinics, drawing on data from 55 countries and more than 500 clinics. Lipid clinics deliver specialised diagnostics, lifestyle management and evidence-based lipid-lowering therapy to high-risk patients — including those with familial hypercholesterolaemia, markedly elevated lipoprotein(a), statin intolerance, refractory LDL cholesterol, severe hypertriglyceridaemia and other rare or complex lipid disorders — to prevent atherosclerotic cardiovascular disease and acute pancreatitis. The statement defines lipid clinics across four tiers and offers practical guidance on staffing, referral criteria, Lp(a) and genetic testing, quality monitoring and funding, highlighting the major differences between countries by income level. The authors — including Jeanine Roeters van Lennep (Erasmus MC) — call for national and international harmonisation so that patients everywhere receive equitable, high-quality lipid care.

Effects of semaglutide on mortality, cardiovascular, and kidney outcomes across the cardio-kidney-metabolic continuum

a systematic review and meta-analysis.

Systematic review and meta-analysis of 8 randomised trials (39,204 patients) on semaglutide versus placebo across the full cardio-kidney-metabolic (CKM) spectrum. Semaglutide significantly reduced all-cause mortality (HR 0.84; 95% CI 0.77-0.92), cardiovascular mortality (HR 0.83), MACE (HR 0.82), non-fatal myocardial infarction (HR 0.75), worsening heart failure (HR 0.84) and adverse kidney outcomes (HR 0.83). No significant effect on non-fatal stroke. The breadth of CKM benefit — kidney, heart and mortality together — distinguishes semaglutide from many other classes and aligns with the recognition of CKM as an integrated disease entity.

Lipoprotein(a) Levels, Risk of Cardiovascular Events and Benefit of Evolocumab

Findings From the VESALIUS-CV Trial.

Prespecified analysis of VESALIUS-CV (n=7,557 patients with atherosclerosis or high-risk diabetes, without prior MI or stroke; median follow-up 4.6 years). Higher baseline Lp(a) was associated with more major coronary events (HR 1.15 per 100 nmol/L; 95% CI 1.05-1.26), particularly myocardial infarction (HR 1.23), but not with ischaemic stroke. After 48 weeks, evolocumab reduced LDL-C by 66.8 mg/dL and Lp(a) by 38.0 nmol/L in patients with baseline Lp(a) >105 nmol/L. The relative risk reduction of major coronary events was similar across Lp(a) strata (~41% high vs ~35% low; p-interaction 0.45), but the absolute reduction was greater with elevated Lp(a) (3.7% vs 2.5%; NNT 28 vs 40 over 5 years). Lp(a) remains an independent risk factor in primary prevention, with evolocumab effective regardless of baseline level.

Familial hypercholesterolaemia in children and adolescents

a European Atherosclerosis Society consensus statement.

European Atherosclerosis Society consensus statement on familial hypercholesterolaemia (FH) in children and adolescents. Heterozygous FH affects about 1 in 300 worldwide; homozygous FH about 1 in 300,000. Early diagnosis and treatment in childhood can normalise life expectancy, but underdiagnosis and undertreatment remain major challenges. The statement provides: (1) a call for all countries to establish paediatric FH screening programmes; (2) revised diagnostic criteria because current ones often miss genetically confirmed cases; (3) updated LDL-C treatment goals; (4) guidance to start lipid-lowering therapy in HeFH before puberty and in HoFH from age 6 where needed; (5) treatment algorithms and recommendations for smooth transition to adult care.

Obicetrapib and lipoprotein(a) levels in patients at high cardiovascular risk

a pooled analysis of trials.

In a pooled analysis of trials in 2,356 high-risk patients (heterozygous FH or established ASCVD), the selective CETP inhibitor obicetrapib 10 mg daily lowered LDL-C by 37%, apoB by 21% and Lp(a) by 37% versus placebo at 12 weeks. Notably, the absolute Lp(a) reduction was similar in patients with mildly and with markedly elevated Lp(a). Obicetrapib thus offers an oral option for patients with mildly elevated Lp(a) who are unlikely to qualify for costlier RNA-targeted Lp(a) therapies.

Outcomes in the BETAMI-DANBLOCK trial compared with a Norwegian nationwide myocardial infarction population.

Comparison of participants in the BETAMI (n=2,867) and DANBLOCK (n=2,707) trials with the Norwegian nationwide myocardial infarction registry (NORMI, n=20,804) — all patients with recent MI, LVEF ≥40% and no heart failure. NORMI patients were older on average (66 vs 63 years) and had more diabetes, prior coronary disease and LVEF 40-49%. Absolute 3-year risks were higher in NORMI (mortality/MI 12.0%) than in the trials (7.7-7.8%). A transportability analysis (reweighting the trial population to NORMI characteristics) showed that the beta-blocker treatment effect remained consistent. BETAMI-DANBLOCK findings therefore generalise to the broader Norwegian — and by extension European — post-MI population.

Pulmonary embolism epidemiology

trends, risk factors, comorbidities, and clinical implications.

EHJ review of acute pulmonary embolism (PE) epidemiology. As ageing populations live longer with chronic diseases associated with venous thromboembolism, PE remains a major public health challenge. Like myocardial infarction and stroke, PE is linked to established cardiovascular risk factors — age, obesity, smoking and chronic inflammatory conditions. Yet population-based primary and secondary prevention strategies remain limited. The authors call for a comprehensive public-health approach that addresses not only acute events and transient risk factors but also community-level risk assessment and long-term prevention, supported by improved clinician education and public awareness.

Renal-diabetic overlap in pulmonary arterial hypertension.

Retrospective international cohort of 555 incident PAH patients (diagnosed 2001-2023). 42% (n=234) had chronic kidney disease and/or diabetes (renal-diabetic, RD): 45 DM only, 135 CKD only, 54 both. RD patients were older, had greater comorbidity burden, worse WHO functional class and higher pulmonary artery wedge pressure. At PAH diagnosis, RD patients were less often treated with endothelin receptor antagonists (61% vs 69%) and more often with single-agent therapy (55% vs 45%). Over 2.5 years of follow-up, the composite of death or PAH hospitalisation was significantly higher in RD (HR 1.45; 95% CI 1.07-1.98), as was all-cause mortality (HR 1.47). PAH with renal-diabetic overlap is common, under-treated and prognostically worse.

Shared pathophysiological mechanisms between diabetes and calcific aortic valve disease

an immunometabolic perspective.

Review of the immunometabolic mechanisms linking diabetes mellitus to accelerated calcific aortic valve disease (CAVD). Diabetes consistently increases incident aortic stenosis risk (HR 1.3-1.7), calcification burden and disease severity, independent of traditional risk factors. The authors delineate seven overlapping pathways: valvular interstitial cell phenotypic switching driven by hyperglycaemia and insulin resistance, AGE-RAGE signalling, oxidative stress, NLRP3-IL-1β inflammasome activation, endothelial dysfunction, BMP-Runx2-Wnt-Notch osteogenic reprogramming, and CKD-mineralocorticoid receptor cross-talk. Metformin, SGLT2 inhibitors, IL-1β/NLRP3 inhibitors and Lp(a)-lowering strategies are proposed candidates for clinical evaluation. The framework argues for valve-focused randomised trials in diabetic CAVD.

The Kidney in the Middle

KDIGO Guidelines Address Multiple Key Components of Cardiovascular-Kidney-Metabolic Syndrome.

Review of KDIGO guidelines addressing the cardiovascular-kidney-metabolic (CKM) syndrome — formally recognised by the American Heart Association in 2023 as the integrated entity linking chronic kidney disease with obesity, diabetes, hypertension, dyslipidaemia, and cardiovascular disease. The review synthesises relevant KDIGO Clinical Practice Guidelines (CKD, blood pressure, diabetes, lipids), the upcoming guideline on heart failure in CKD, and Controversies Conference reports on obesity and CKD prevention. Core themes: early detection and intervention, personalised management of kidney and cardiovascular risk, and multidisciplinary care. KDIGO provides a robust framework for clinical practice and research priorities in patients at risk for or with CKM syndrome.

Pathophysiology, prevention, and management of coronary microvascular obstruction.

Clinical consensus statement on the pathophysiology, prevention, and management of microvascular obstruction ('no-reflow') after primary PCI in STEMI. Despite timely revascularization, suboptimal myocardial reperfusion persists in up to 60% of cases, with major risk of adverse LV remodeling, heart failure and death. Pharmacological therapies (intracoronary adenosine, nitroprusside) show unclear benefit. Non-pharmacological strategies — ischemic postconditioning, supersaturated oxygen therapy, mechanical LV unloading — show promise but require large-scale RCT validation. The statement underscores the need for better risk stratification and novel microvasculature-targeted therapies.

Women's heart centres

a clinical consensus statement of the European Association of Cardiovascular Imaging (EACVI), the European Association of Percutaneous Cardiovascular Interventions (EAPCI), the Heart Failure Association (HFA), and the Association for Acute CardioVascular Care (ACVC) of the ESC.

Joint clinical consensus statement from EACVI, EAPCI, HFA and ACVC on establishing Women's Heart Centres (WHC) in Europe. WHCs are conceived as hub-and-spoke networks embedded in existing cardiovascular systems, delivering multidisciplinary, sex-sensitive care across the life course. Key domains: INOCA/MINOCA, cardio-obstetrics, cardio-oncology, autoimmune disease in women, mental health, cardiac rehabilitation. The document defines referral pathways, operational standards and core competencies; available evidence suggests improved diagnostic precision, risk factor control and patient-reported outcomes.

SGLT2 inhibitors are associated with reductions in epicardial adipose tissue volume and thickness

a meta-analysis.

Systematic review and meta-analysis of 11 studies (284 patients) on the effect of SGLT2 inhibitors on epicardial adipose tissue (EAT). SGLT2 inhibitor therapy produced a significant reduction in EAT versus conventional antidiabetic therapy (Hedges g -1.64; 95% CI -2.10 to -1.18), consistent across thickness (echocardiography) and volume (CT/CMR) modalities. Modest reductions in BMI and systolic blood pressure were also observed. EAT reduction may contribute to the broad cardiovascular benefits of SGLT2 inhibitors.

Pulsed Field Ablation for the Interventional Treatment of Atrial Fibrillation. A Scientific Statement of the European Heart Rhythm Association (EHRA) of the ESC, the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS), the Latin American Heart Rhythm Society (LAHRS) and the Canadian Heart Rhythm Society (CHRS).

International scientific statement from EHRA, HRS, APHRS, LAHRS and CHRS on pulsed field ablation (PFA) for atrial fibrillation. Through irreversible electroporation, PFA achieves myocardial ablation while preserving surrounding structures such as nerves, vasculature and the esophagus. Randomized trials demonstrate efficacy comparable to radiofrequency and cryoballoon ablation, with clear advantages in safety and procedural efficiency. The statement summarizes biophysics, technology and clinical evidence and provides practical guidance for clinical implementation and operator training.

Glucagon-Like Peptide-1 Receptor Agonists in Patients with Heart Failure with Reduced Ejection Fraction.

Multicenter retrospective cohort (UT Southwestern) of 2,550 propensity-matched patients with heart failure with reduced ejection fraction (HFrEF, LVEF ≤40%). GLP-1 receptor agonist therapy (semaglutide, tirzepatide, or liraglutide) was associated with 32% lower 1-year all-cause mortality (7.1% vs 10.2%; OR 0.68; HR 0.54) and fewer acute decompensated heart failure hospitalizations (27.7% vs 32.8%; OR 0.79), without an increase in arrhythmic events or new ACS/stroke. Prospective randomized trials are needed before GLP-1 RAs can be recommended in HFrEF.

In Vivo Base Editing of PCSK9 with VERVE-102 for Hypercholesterolemia

VERVE-102 is a base-editing therapy that permanently inactivates the hepatic PCSK9 gene with a single infusion — an adenine base-editor mRNA plus a guide RNA in a GalNAc lipid nanoparticle. In this phase 1 study of 35 patients with heterozygous familial hypercholesterolaemia or premature coronary artery disease, PCSK9 protein fell dose-dependently by 51% to 88% and LDL cholesterol by up to 62%, with a durable effect after one dose. No dose-limiting toxic effects occurred; there were mild-to-moderate infusion reactions and transient ALT elevations (and one aspiration pneumonitis in a patient with reflux). A one-time, durable LDL reduction thus comes into view as a treatment concept.

Secondary Prevention After Coronary Artery Bypass Graft Surgery

2026 Update: A Scientific Statement From the American Heart Association

First AHA scientific statement on post-CABG secondary prevention since 2015, published in Circulation in the week after HF26. Covers lipid lowering (including PCSK9 inhibitors / inclisiran in this population), antiplatelet/anticoagulation, BP targets, diabetes and CKM management, cardiac rehabilitation, and post-discharge follow-up — separating evidence-based from consensus recommendations throughout. Reference document for the multidisciplinary CABG follow-up team.

One-year multicenter prospective real-world study of vericiguat effectiveness and safety in Spain

the VERISEC registry

VERISEC (n=835, 41 Spanish centres) confirms vericiguat's real-world benefit in HFrEF after recent decompensation. Over 12 months on top of >90% SGLT2i / >85% RAASi / ~80% MRA / 91% beta-blocker background, NT-proBNP fell from 3,532 to 2,292 pg/mL (p<0.001), LVEF rose from 30.3% to 35.4%, NYHA class improved, and HF decompensations requiring IV diuretics halved (1.34 → 0.65 per year). 13.4% discontinued, mostly for symptomatic hypotension; higher baseline NT-proBNP predicted discontinuation.

Does the global prevalence of heart failure now exceed 600 million people? From guesswork to evidence

Cleland, Lainscak, Pellicori editorial (EHJ, during HF26) revises global heart failure prevalence: historical ~60M figures reflect symptomatic HF in registries, but contemporary population-based echo screening including stage A/B, HFpEF and structural/functional abnormalities consistently finds 8–12% of older adults — implying a global population >600 million. Calls for international case-definition consensus, routine NT-proBNP + echo screening in primary care, and HF prevalence in national CV registries. Frames HF as a population-health emergency rather than a sub-specialty problem.

Predictors of Long-Term Outcomes in Hypertrophic Cardiomyopathy

The NHLBI HCM Registry (HCMR)

HCMR (NHLBI HCM Registry) prospectively enrolled 2,750 patients with HCM at 44 expert sites across North America and Europe; all underwent contrast CMR, biomarker/genotyping bloodwork, and structured history. Median follow-up >7 years. An integrated multidimensional model (combining clinical, imaging, genetic and biomarker data via elastic-net selection) outperforms current SCD-only risk prediction, capturing patients at risk of HF events and transplant that are under-recognized today. Likely reduces both unnecessary ICDs (overtreatment) and avoidable deaths (undertreatment). Important context for HCM clinics now selecting candidates for mavacamten/aficamten therapy.

Sotatercept for Combined Post- and Pre-capillary Pulmonary Hypertension Associated With Heart Failure

Results from the Phase 2, Randomized, Placebo-Controlled CADENCE Study

CADENCE (n=164, multicentre, randomized, placebo-controlled phase 2) tested sotatercept (activin signalling inhibitor) in patients with combined post- and pre-capillary pulmonary hypertension (CpcPH) in HFpEF. PVR at week 24 dropped by −1.02 Wood units (95% CI −1.81 to −0.23; p=0.004) at the 0.3 mg/kg dose and −0.75 (p=0.024) at 0.7 mg/kg. Mean PAP fell by ~9 mmHg, wedge pressure by 2.5–3 mmHg, 6-min walk improved 20.3 m at the lower dose. Proof of concept for the first therapy in CpcPH-HFpEF, a high-mortality phenotype without approved treatment. Major extension of the sotatercept (WINREVAIR) platform from PAH into HFpEF-PH. (Originally presented at ACC.26 in March; full Circulation publication during HF26.)

SUBCUT HF II — At-home subcutaneous furosemide reduces hospital days versus inpatient intravenous furosemide in patients admitted with heart failure-associated edema

a multicentre randomised controlled trial

SUBCUT HF II (UK, 20 NHS sites, n=170) compared at-home subcutaneous furosemide via the Lasix ONYU patch-pump (80 mg over 5h) versus continued inpatient IV furosemide in patients admitted with HF-associated edema. At-home treatment yielded +4 days alive-and-out-of-hospital at 30 days (p<0.001) and reduced index hospitalization length by 5.5 days (p<0.001), sustained at 60 days, with equivalent safety. Lasix ONYU was FDA-approved October 2025; SUBCUT HF II provides the supporting RCT evidence. Direct implications for cardiology capacity planning.

Incident cancer in heart failure, myocardial infarction or both

a report from a global federated research network

Federated cohort study (TriNetX) of 120,783 HF patients and 7,896 AMI patients propensity-matched 1:1 to controls without HF/AMI, excluding prior/concurrent cancer. New cancer diagnoses starting 6 months after index hospitalization showed strikingly elevated risk: HF HR 2.80 (95% CI 2.69–2.91); AMI HR 2.02 (95% CI 1.71–2.39); both p<0.001. The excess risk was much greater for haematologic malignancies (HF HR 6.78; AMI HR 4.45) than solid tumours. HFpEF carried slightly higher cancer incidence than HFrEF/HFmrEF (HR 1.10). Hypothesis-generating finding in 'reverse cardio-oncology' — possible mechanisms include shared inflammatory pathways and clonal haematopoiesis. Prospective confirmation needed before screening implications.

Anthropometric adiposity measures and natriuretic peptides in heart failure screening

population-based evidence from the PORTHOS study

PORTHOS (Portugal, population-based, age ≥50, n=2,498) shows NT-proBNP is systematically lower in obesity — ~50 pg/mL lower per 5 kg/m² BMI increase. Obese participants with NT-proBNP <125 pg/mL had higher odds of HF symptoms (OR 1.97) and echo abnormalities (OR 3.63) than lean participants above the cut-off, despite being 9 years younger and having 4x lower NT-proBNP (59 vs 235 pg/mL). Fixed cut-offs miss HF in obesity; primary-care screening pathways need adjustment.

Prevalence and Predictors of High Inflammatory Risk in Heart Failure Subtypes

Findings From the Global POSEIDON Study

POSEIDON enrolled 18,904 individuals at 317 sites in 18 countries (2023–2025); 11,809 had HF with hsCRP available. Elevated hsCRP (≥2 mg/L) was present in ~38% of patients across HFpEF, HFmrEF and HFrEF — strikingly consistent across the EF spectrum. Patients with elevated hsCRP were more likely female with a cardio-kidney-metabolic phenotype: CKD, obesity, worse NYHA, higher NT-proBNP. Smoking, autoimmune/inflammatory disease, obesity and reduced eGFR were independent predictors. The findings define the target population for IL-6 trials (ATHENA, HERMES with ziltivekimab) also announced at HF26.

Physical Activity in Pediatric Cardiomyopathies

Moving for Health: A Scientific Statement From the American Heart Association

Decades of risk-averse guidance have left children with cardiomyopathy sedentary, with poor cardiorespiratory fitness and added cardiometabolic risk. This AHA Scientific Statement provides an evidence-based framework to actively promote physical activity in paediatric hypertrophic, dilated, restrictive and arrhythmogenic cardiomyopathy. Newer data suggest sudden cardiac death risk in selected patients is not higher with exercise than with inactivity, and physical activity may even support reverse remodelling. The statement offers a practical framework for risk stratification and personalised exercise prescription.

Cardiovascular disease in Sickle cell

mechanisms, diagnostics and therapeutic advances

A contemporary review of cardiovascular complications in sickle cell disease: myocardial dysfunction, pulmonary hypertension, cardiac iron overload, arrhythmias, myocardial infarction, stroke and sudden death. They remain under-recognised despite their growing role in morbidity and premature mortality. Cardiac MRI with T2* mapping and ECV sequences, speckle-tracking echocardiography and invasive exercise testing reveal a distinct phenotype of restrictive cardiomyopathy with high-output heart failure. The review provides SCD-specific risk stratification and treatment algorithms.

Guideline-recommended medical therapy efficacy according to use of digoxin

a study-level meta-analysis combining DECISION, DIGIT-HF and DIG

A study-level meta-analysis pooling DECISION, DIGIT-HF and DIG (n=9,013) shows digitalis glycosides reduce CV death or first worsening HF event (HR 0.85; 95% CI 0.80–0.90; p<0.001) and time to first worsening HF event (HR 0.75; p<0.001), with consistent benefit on top of contemporary RALES/EMPHASIS-HF/PARADIGM-HF/DAPA-HF backbones. Population-level evidence reopening the case for digitalis as an add-on in symptomatic HF(m)rEF despite four-pillar therapy.

Angiotensin Receptor Neprilysin Inhibitor in Heart Failure with Preserved Ejection Fraction and Secondary Mitral Regurgitation

the PRAISE-MR Randomized Trial

PRAISE-MR is the first medical-therapy trial demonstrating exercise-hemodynamic benefit in HFpEF with atrial functional mitral regurgitation (AFMR). In 84 patients randomized to sacubitril-valsartan or standard of care, the 6-month change in exercise mPAP/CO slope improved by 0.93 mmHg/L/min with sacubitril-valsartan (95% CI 0.07–1.80; p=0.035). Peak VO2, KCCQ score, NT-proBNP, LA volume and AFMR severity all improved. The findings position ARNI as a credible disease-modifying option for HFpEF + AFMR, alongside transcatheter mitral repair as evidence emerges.

Digoxin in Patients With Symptomatic Rheumatic Heart Disease

Dig-RHD is the first RCT of digoxin in rheumatic heart disease. 1,769 patients across 12 Indian tertiary centers (mean age 46, 72% female, 70% AF, 90% NYHA II–IV, mostly with mixed valve lesions) were randomized to digoxin 0.125–0.25 mg/day or placebo and followed a median 2.1 years. The primary composite of all-cause death or new-onset/worsening HF occurred in 31.4% (digoxin) vs 35.5% (placebo) — HR 0.82; 95% CI 0.69–0.96. Practice-changing for the Global South where RHD remains the leading cause of HF; relevant for migrant populations with chronic rheumatic valve disease in Western settings.

Blinded withdrawal of randomized treatment with low-dose digoxin or placebo in patients with heart failure

the DECISION trial

Pre-specified DECISION substudy: 587 patients on active treatment (digoxin or placebo) underwent blinded withdrawal with 6-week in-person follow-up. Pre-withdrawal event rates were similar between groups. Post-withdrawal, digoxin-withdrawn patients had a sharp increase in CV death/worsening HF events (42.8 vs 5.9 per 100 patient-years; RR 7.37; 95% CI 1.56–34.88; p=0.012), accompanied by rising heart rate, falling SBP and rising NT-proBNP. Discontinuing digoxin after long-term exposure is associated with clinical deterioration — a clinically relevant caution for deprescribing reviews.

Low-dose digoxin in patients with heart failure with reduced or mildly reduced ejection fraction

a randomized controlled trial

DECISION (n=1,001, 43 Dutch sites, median 36.5-month follow-up) is the first major modern RCT of low-dose digoxin in contemporary HF(m)rEF on guideline-directed therapy. The primary composite of worsening HF events plus CV mortality was lower with digoxin (RR 0.81; 95% CI 0.61–1.07) but did not reach statistical significance (p=0.133). Worsening HF events trended lower (RR 0.76); CV mortality was unchanged. Drug was well tolerated. Pooled with DIGIT-HF and DIG (n=9,013), digitalis glycosides did significantly reduce the composite (HR 0.85; p<0.001), reopening the case for digitalis as a cheap, safe add-on in HF(m)rEF.

The microRNA inhibitor CDR132L in patients with reduced left ventricular ejection fraction after myocardial infarction

a randomized phase 2 trial

HF-REVERT (n=294) is the first phase 2 randomized trial of an antisense microRNA inhibitor in cardiology. CDR132L (anti-miR-132) given as three IV doses 3–14 days post-MI did not improve the primary endpoint (% change in LVESVi at 6 months) nor any secondary endpoint over placebo. The drug was well tolerated. Pre-specified exploratory analyses suggest potential benefit in patients with marked adverse remodeling at baseline — a hypothesis-generating signal worth pursuing in chronic HF populations. Important null finding for the cardiac RNA-therapeutics pipeline.

Subcutaneous Defibrillator Implantation With or Without Defibrillation Test

The Primary Results of the Randomized PRAETORIAN-DFT Trial

The multinational PRAETORIAN-DFT RCT randomised 965 subcutaneous ICD recipients across 37 centres to defibrillation testing versus no testing — using the PRAETORIAN score (based on chest X-ray) to assess implant position in the no-DFT arm. First-shock failure for spontaneous ventricular arrhythmias was non-inferior without DFT, with comparable mortality and revisions. Routine defibrillation testing can therefore be omitted in patients with a favourable PRAETORIAN score, reducing implant-related risk.

Stroke and Bleeding Risks With Non-Vitamin K Oral Anticoagulants in Nonvalvular Atrial Fibrillation.

A cohort study in the FDA Sentinel System of >173,000 NVAF patients aged 21-64 found that rivaroxaban was associated with higher major extracranial bleeding (HR 1.91) and gastrointestinal bleeding (HR 1.92) versus apixaban, with no difference in thromboembolic stroke. Dabigatran carried a higher thromboembolic stroke risk than both rivaroxaban and apixaban. Apixaban emerged with the most favourable benefit-harm profile — extending Medicare findings into a younger AF population.

Kidney function and risk of heart failure in older adults

findings from a prospective cohort study

A prospective cohort analysis nested in the ASPREE trial and its extension study (17,834 older adults) examined whether elevated urine albumin-creatinine ratio (UACR) or reduced eGFR predicted heart failure hospitalisation or death. Over a median 8.6-year follow-up, 354 (1.98%) had a first HF hospitalisation and 147 (0.82%) died from HF. Albuminuria (UACR ≥3.0 mg/mmol; 11.3% of the cohort) was associated with higher risk of HF events. Routine kidney screening in primary care looks valuable for cardiovascular risk stratification in older adults.

Combined transcatheter mitral and tricuspid edge-to-edge repair or tricuspid edge-to-edge repair alone in moderate mitral regurgitation

a propensity-matched analysis.

In the EuroTR registry of 3,100 patients with severe tricuspid regurgitation, 30% also had moderate mitral regurgitation — associated with higher 2-year mortality (37% vs 23%). After propensity score matching (217 pairs), concomitant mitral TEER added to tricuspid TEER produced greater TR reduction, better NYHA class and 6-minute walk distance, and significantly higher survival (87% vs 76% at 1 year; 81% vs 70% at 2 years). On multivariable analysis, moderate MR predicted death (HR 1.81) and combined M-TEER predicted survival (HR 0.46). Hypothesis-generating — a dedicated RCT is needed.

Risk factors for atherosclerotic cardiovascular disease in individuals with heterozygous familial hypercholesterolemia

a systematic review and meta-analysis.

A systematic review and meta-analysis (21 studies, 23,613 genetically confirmed heterozygous FH patients, 3,489 cardiovascular events) showed independent associations between ASCVD and hypertension (effect size 0.41), male sex (0.33), smoking (0.32), Lp(a) (0.22), age (0.21), BMI (0.11), triglycerides (0.08) and LDL-C (0.02). Beyond intensive LDL lowering, aggressive management of classic risk factors — especially blood pressure and smoking — is essential to limit residual risk in this high-risk group.

Extensive pregnancy-related off-treatment time in women with familial hypercholesterolaemia

A Norwegian cohort within the FH-FEMINA study followed 27 women with familial hypercholesterolaemia from 36 weeks of gestation until one year postpartum or end of breastfeeding. Median pregnancy-related off-treatment time per woman was 2.9 years (range 0.8–12) across all childbirths. The pregnancy itself accounted for only 42% of off-treatment time; the pre- and post-pregnancy windows together accounted for 58%. Including untreated years in childhood and before diagnosis, lifelong off-treatment time reached a median of 66% of total lifespan. The authors — including Jeanine Roeters van Lennep (Erasmus MC) and Janneke Mulder, both active in the Dutch LEEFH cascade screening programme — call for earlier FH diagnosis in girls, prompt resumption of lipid-lowering therapy immediately after breastfeeding and between pregnancies, and urgently needed evidence on statin safety during pregnancy and lactation.

Sex differences in pharmacological treatment of heart failure

a meta-analysis of randomized trials.

A meta-analysis of 139 heart failure RCTs (292,027 patients, 28.1% women) tested whether pharmacological efficacy differs by sex. Across 78 trials reporting sex-stratified results the primary-endpoint effect was identical in women and men (delta ln[REM] 0.00; 95% CI −0.04 to 0.03), and meta-regression found no association between the proportion of women enrolled and treatment effect. Decades of female under-representation are therefore unlikely to have masked clinically meaningful sex differences — though better gender balance in HF trials remains ethically and socially essential.

Continuation vs Switching Direct Oral Anticoagulant Therapy After Breakthrough Stroke.

A registry-based emulated target trial of 1,006 AF patients with ischaemic stroke during DOAC therapy: 463 continued the same DOAC and 543 switched. After IPTW adjustment, 90-day net clinical benefit was 4.9% with switching versus 5.1% with continuation, a difference of −0.3 percentage points (90% CI −2.7 to 2.1) — within the prespecified non-inferiority margin. Recurrent ischaemic events, intracerebral haemorrhage, all-cause mortality and vascular death did not differ. After a breakthrough stroke on DOAC, switching is not better than continuing — the upfront DOAC choice matters more.

Multi-modality non-invasive cardiovascular screening and sex-specific outcomes

the Viborg Screening Program.

The Danish Viborg Screening Program invited all 67-year-olds for population-based screening (carotid plaque, lower-limb arterial disease, abdominal aortic aneurysm, hypertension, arrhythmia/ischaemia and diabetes). Across 5,412 invitees versus 16,236 matched controls, 5-year all-cause mortality was significantly lower (6.9% vs 8.9%; HR 0.76; number-needed-to-invite 49). Benefit was seen in both sexes and was strongest in those without prior CVD (HR 0.70); major adverse limb events also fell (HR 0.70).

RAAS blockade in the kidney Life-Cycle - Treatment Standard.

An ERA-EDTA treatment-standard review on RAAS blockade across the kidney life cycle. ACE inhibitors, ARBs, direct renin inhibitors and mineralocorticoid receptor antagonists remain a cornerstone in proteinuric CKD and even in advanced stages, while benefit in non-proteinuric disease is limited. Non-steroidal MRAs such as finerenone add renal and cardiovascular protection in diabetes and CKD. In dialysis populations RAAS blockade may preserve residual kidney function; in kidney transplantation, early initiation may improve graft and patient survival. SGLT2 inhibitors and GLP-1 receptor agonists complement rather than replace RAAS blockade.

Stereotactic arrhythmia radioablation for refractory ventricular tachycardia

the STOPSTORM.eu study.

The European STOPSTORM registry followed 193 patients (88% male, 53% non-ischaemic cardiomyopathy) treated with stereotactic arrhythmia radioablation (STAR) for refractory ventricular tachycardia. Among 107 patients with ≥6-month follow-up, median VT burden fell 80% over the six months after STAR and 72% remained free of ICD shocks. Twelve serious adverse events were adjudicated as possibly or probably treatment-related (including pericardial effusion and coronary events); 12-month overall survival was 77%.

Three Low-Dose Antihypertensive Agents in a Single Pill after Intracerebral Hemorrhage.

In a multinational double-blind RCT of 1670 patients with prior intracerebral haemorrhage, a once-daily low-dose triple pill (telmisartan 20 mg, amlodipine 2.5 mg and indapamide 1.25 mg) added to standard care reduced recurrent stroke by 39% (4.6% vs 7.4%; HR 0.61) over 2.5 years, with mean systolic BP of 127 vs 138 mmHg. Major cardiovascular events were also lower (6.6% vs 9.8%). Early discontinuation for adverse events — mainly serum creatinine rises — was more common with the triple pill (13.6% vs 6.0%).

Early atheroma prevention

a cost-effective approach to healthy cardiovascular ageing

With annual ASCVD deaths projected to rise from 20.5 million (2025) to 35.6 million (2050), the authors make the Lancet case for earlier and longer primary prevention — aimed at slowing atheroma formation rather than intervening only once disease becomes symptomatic. The piece frames prevention as a life-course intervention and provides relevant context for conversations about early statin initiation, Lp(a) screening, and lifestyle measures.

Automated Echocardiographic Detection of Congenital Heart Disease Using Artificial Intelligence

EchoFocus-CHD is a multi-task AI model that automatically detects 12 critical and 8 non-critical congenital heart lesions on standard echocardiography. On an external cohort the model matched expert interpretation — with the promise of extending scarce paediatric echo expertise beyond academic centres. A concrete example of where AI-assisted imaging can rapidly deliver clinical value in primary care and smaller hospitals.

Assessment for Long-Term Cardiovascular Disease Risk in Pregnancy

Adverse pregnancy outcomes — hypertensive disorders, gestational diabetes, preterm birth, SGA — complicate nearly one in five pregnancies and are associated with both short- and long-term maternal CV risk. This review consolidates the growing consensus that pregnancy is a natural stress test and the postpartum period an opportunistic window for targeted CV risk screening and lifestyle counselling. It argues for formally embedding pregnancy history into cardiovascular risk assessment.

Sotatercept for Combined Post- and Pre-capillary Pulmonary Hypertension Associated With Heart Failure

Results from the Phase 2, Randomized, Placebo-Controlled CADENCE Study

In this phase 2, placebo-controlled trial (n=164), sotatercept lowered pulmonary vascular resistance at week 24 in patients with combined post- and pre-capillary pulmonary hypertension associated with HFpEF. The median placebo-adjusted decline was largest in the 0.3 mg/kg arm. Until now no proven therapy existed for this CpcPH–HFpEF population, which involves remodeling in both the heart and pulmonary vasculature.

The Role of Atrial Pacing Support in Cardiac Resynchronization Therapy

A Non-Inferiority Randomized Trial

In this Italian multicenter RCT (n=636), a two-lead CRT-DX system with atrial sensing via a floating dipole on the RV lead was non-inferior to standard three-lead CRT-D on the 1-year composite of mortality, cardiovascular hospitalisation, and lead-related complications. For CRT-D candidates without sinus node dysfunction, the simplification is clinically appealing: fewer leads, fewer complications.

2026 Dietary Guidance to Improve Cardiovascular Health

A Scientific Statement From the American Heart Association

This AHA scientific statement updates food-based guidance for cardiovascular health with seven practical pillars: energy balance, abundant vegetables and fruit, mostly whole grains, healthy protein sources, unsaturated over saturated fats, less ultra-processed food, and less sodium and added sugar. It deliberately emphasises dietary pattern over isolated nutrients — relevant simultaneously for prevention, CKM syndrome, and oncology.

Cardiovascular–Kidney–Metabolic Syndrome Stages, Echocardiographic Characteristics, and Heart Failure Risk

The Atherosclerosis Risk in Communities Study

In 5,646 older ARIC participants (66–90), CKM syndrome staging using the AHA framework showed a clear gradient: higher stages tracked with greater echocardiographic remodelling and significantly increased incident heart failure over follow-up. The results validate the CKM framework as a clinically useful risk model in older adults — the very group where HF prevention yields the highest absolute benefit.

Two Trials Comparing Conduction System Pacing and Biventricular Pacing

Two new RCTs compare conduction system pacing (chiefly left bundle-branch area pacing) with conventional biventricular pacing in heart failure patients with LBBB. Earlier observational data suggested superior electrical resynchronisation and larger LVEF gains with CSP, fuelling rapid clinical adoption. These trials finally test whether the physiologically attractive approach actually outperforms BiVP on hard endpoints.

Effect of APOC3 Inhibition with Olezarsen on Coronary Atherosclerosis

Essence–TIMI 73b Imaging Study

This CCTA sub-study of Essence-TIMI 73b showed that olezarsen — an APOC3 antisense oligonucleotide — lowered triglycerides by ~60% and remnant cholesterol by ~70%, with neutral LDL-C and ~15% apoB reduction. Over 12 months in patients with moderate hypertriglyceridemia and non-calcified coronary plaque, olezarsen produced a placebo-adjusted reduction in non-calcified plaque volume. It provides some of the first imaging evidence that triglyceride-directed therapy favorably modifies coronary atherosclerosis.

Low-Dose Rivaroxaban to Prevent Left Ventricular Thrombosis After Anterior Myocardial Infarction

This French multicenter randomized trial assessed whether adding low-dose rivaroxaban to dual antiplatelet therapy reduces left ventricular thrombus incidence at one month in anterior STEMI patients. The strategy targets a persistent problem: subclinical LV thrombus soon after anterior MI with silent embolic implications. The results support targeted thromboprophylaxis in this high-risk subgroup without disproportionate bleeding.

2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Dyslipidemia

A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines

The 2026 ACC/AHA dyslipidemia guideline retires the 2018 cholesterol document and broadens scope to hypertriglyceridemia and elevated lipoprotein(a). Non-HDL-C and apoB gain ground as secondary targets, LDL goals tighten for high-risk groups, and Lp(a) gets formal standing in risk assessment. Clinicians should anticipate broader lipid panels and more frequent escalation to PCSK9 inhibitors and emerging Lp(a)-lowering therapies.

Memantine for Premature Atrial Contractions

A Phase 2 Randomized Clinical Trial

In this phase 2 double-blind randomized trial, memantine — an NMDA-receptor antagonist — suppressed premature atrial contractions in symptomatic adults with ≥1,000 PACs per 24 h. The result opens a genuinely new pharmacological route for atrial arrhythmia, grounded in the recently identified cardiac glutamatergic system. If PAC reduction translates into downstream AF and stroke benefit, it could reshape atrial arrhythmia treatment.

Prehospital Heparin Administration in Patients With STEMI Undergoing Primary PCI

HEPARIN STEMI Randomized Controlled Trial

This single-center RCT in 593 STEMI patients found that unfractionated heparin (70–100 IU/kg) given at first medical contact — prior to PCI-center arrival — significantly improved TIMI 2–3 flow in the infarct-related artery at initial angiography compared with standard UFH at PCI. BARC 3–5 bleeding was similar. The trial supports prehospital heparin as a simple, low-cost reperfusion strategy ahead of primary PCI.

Wearable devices and cardiovascular health

revolutionizing remote monitoring and disease prevention.

This EHJ review maps the current landscape of wearables (smartwatches and activity trackers) in cardiovascular care, from lifestyle coaching to continuous monitoring of heart failure and arrhythmias. It highlights the main barriers — variability in device methodology and validation, EHR incompatibility, and lack of standardised clinical workflows — and discusses AI-assisted interpretation. It offers practical guidance for clinicians integrating wearable data into routine practice.

Lp(a) Has Specific Effects on Coronary Artery Disease Independent of LDL-C

A Mendelian Randomization Study.

A phenome-wide Mendelian randomisation study in the UK Biobank (n=425,677) identified coronary artery disease (OR 1.36) and HbA1c (β 0.099) as the only direct, causal effects of Lp(a) exposure — independent of LDL-C. Very low Lp(a) was not linked to diabetes, addressing earlier safety concerns about Lp(a)-lowering therapies. Ancestry-specific risk thresholds were identified (86 nmol/L European, 93 nmol/L African). The findings support targeted Lp(a) testing and strengthen the mechanistic case for RNA-based Lp(a) lowering.

Impact of Genetic Testing Among Patients With Familial Hypercholesterolemia on Adverse Cardiovascular Events　- The Hokuriku-Plus Familial Hypercholesterolemia Registry Study.

In the Japanese Hokuriku-Plus registry (n=386 heterozygous FH), 52% of patients underwent genetic testing. These patients achieved lower LDL-C (102 vs 130 mg/dL) and had 34% lower MACE risk (HR 0.66) even after adjusting for LDL-C over 3.9-year median follow-up. The results suggest genetic confirmation itself drives better adherence and treatment intensity, arguing for broader FH genetic testing in clinical practice.

Glucagon-like peptide-1 receptor agonists for prevention of heart failure events in type 2 diabetes and/or obesity.

This meta-analysis of 12 placebo-controlled trials (n=95,023) found GLP-1 receptor agonists reduced heart failure events by 12% (NNT 238), and by 19% (NNT 167) in patients without baseline HF. Semaglutide specifically reduced HF events by 16% overall and by 31% in those without prior HF (NNT 80). Absolute benefits are modest but clinically relevant given the widespread use of GLP-1 therapy in type 2 diabetes and obesity management.

Sex differences in cardiovascular-kidney-metabolic syndrome

the FINE-HEART pooled analysis.

This prespecified pooled analysis of FIDELIO-DKD, FIGARO-DKD and FINEARTS-HF (n=18,991) found women with cardiovascular-kidney-metabolic syndrome were older, had more Stage 4 CKM disease, and received fewer guideline-recommended therapies (aspirin, statins, RAS inhibitors, SGLT2 inhibitors, GLP-1 receptor agonists) than men. Rates of HF hospitalisation or CV death were similar across sexes, but women had 17% lower all-cause mortality. Finerenone was equally effective in both sexes. The results highlight a persistent treatment gap that deserves clinical attention.

Lipoprotein(a) and incident venous thromboembolism in pre- and postmenopausal women, and in men.

In the UK Biobank (≈373,000 participants), Lp(a) ≥ 125 nmol/L was associated with incident venous thromboembolism in premenopausal women (aHR 1.32) and in postmenopausal women on menopausal hormone therapy (aHR 1.48), but not in postmenopausal women without hormones or in men. Oral contraceptive use did not modify the relationship in premenopausal women. The findings suggest sex-hormone status modifies Lp(a)-related VTE risk and support considering Lp(a) before starting hormone therapy.

Evolocumab to Reduce First Major Cardiovascular Events in Patients Without Known Significant Atherosclerosis and With Diabetes

Results From the VESALIUS-CV Trial.

This prespecified VESALIUS-CV subgroup (n=3655 diabetics with LDL-C ≥ 90 mg/dL and no established atherosclerosis) found that evolocumab on top of optimised statin therapy significantly reduced first MACE over a median 4.8 years of follow-up. The JAMA-published analysis pushes PCSK9 inhibition further upstream in high-risk diabetics without prior arterial disease, calcium score ≥ 100, or stenosis ≥ 50%. It strengthens the case for earlier intensive LDL-C lowering in primary prevention for diabetic patients.

Acute eGFR Changes and Their Mediation of Albuminuria Reduction with Empagliflozin and Finerenone.

This prespecified CONFIDENCE analysis (n=790 with T2D, CKD and albuminuria) found the greatest acute day-14 eGFR decline with combination therapy (-6.6 mL/min) vs finerenone alone (-2.1) or empagliflozin alone (-4.8), but declines were reversible. Finerenone's additive UACR-lowering effect was non-haemodynamic, while empagliflozin's effect was partly eGFR-mediated. The results reinforce that initial eGFR dips should not trigger discontinuation and support combination therapy in diabetic CKD.

Volume vs intensity of physical activity and risk of cardiovascular and non-cardiovascular chronic diseases.

Using wrist-accelerometer data from 96,408 UK Biobank participants, a higher share of vigorous activity (%VPA) showed a non-linear inverse association with MACE, atrial fibrillation, type 2 diabetes, CKD, dementia and all-cause mortality — independent of total activity volume. Participants exceeding 4% VPA had 29–61% lower risk of these outcomes. The study suggests exercise intensity deserves more weight in prevention counselling, alongside the traditional focus on weekly duration.

The Liraglutide Effects in Atrial Fibrillation (LEAF) Study.

In this randomized study, 59 overweight or obese patients with (mostly persistent) atrial fibrillation received three months of risk-factor modification with or without liraglutide before catheter ablation. The primary endpoint — reduction of left-atrial epicardial adipose tissue — did not differ significantly between groups. Nonetheless, one-year freedom from AF/atrial flutter was higher with liraglutide (81% vs 54%; p=0.007). The authors suggest pleiotropic GLP-1 effects may offer a novel target for AF treatment, to be confirmed in larger trials.

Left Atrial Appendage Closure or Anticoagulation for Atrial Fibrillation

In CHAMPION-AF, 3,000 patients with non-valvular AF were randomized to WATCHMAN FLX LAA closure or NOAC therapy. At 36 months, the device was noninferior for the primary efficacy endpoint (stroke, CV death, systemic embolism: 5.7% vs 4.8%; P<0.001 for noninferiority) and superior for non-procedural bleeding (45% reduction: 10.9% vs 19.0%; P<0.001). This contrasts with the negative CLOSURE-AF trial and establishes WATCHMAN FLX as the first LAA closure device to demonstrate noninferiority vs NOACs as first-line therapy.

Ultrasound-Facilitated, Catheter-Directed Fibrinolysis for Acute Pulmonary Embolism

In the HI-PEITHO trial, 544 patients with acute intermediate-high-risk PE were randomized to ultrasound-facilitated catheter-directed fibrinolysis (EKOS) vs anticoagulation alone. The primary composite endpoint (PE-related death, cardiorespiratory decompensation, or recurrent PE within 7 days) occurred in 3.7% vs 10.3% — a 61% relative risk reduction (RR 0.4; P=0.005). No intracranial bleeding in either group. First positive hard-outcome trial for catheter-directed intervention in intermediate-risk PE.

Evolocumab Reduces Risk of First Major Cardiovascular Events by 31% in Patients Without Significant Atherosclerosis

Results from VESALIUS-CV

In a subgroup analysis of VESALIUS-CV, 3,655 patients with diabetes but no known significant atherosclerosis were followed for a median of 4.8 years. Evolocumab reduced 3-P MACE by 31% (HR 0.69; P=0.009) and 4-P MACE by 31% (HR 0.69; P=0.001). The effect appeared after 1 year and grew to ~40% reduction thereafter. CV death was reduced by 32% and all-cause mortality by 24%. This supports the use of PCSK9 inhibitors for primary prevention in high-risk diabetes patients.

Intensive Low-density Lipoprotein Cholesterol Targeting in Patients with Atherosclerotic Cardiovascular Disease

In the Ez-PAVE trial, the first randomized head-to-head comparison of LDL-C targets, 3,048 patients with ASCVD were shown to have a 33% lower risk of cardiovascular events with a target of <55 mg/dL vs <70 mg/dL (HR 0.67; P=0.002). At 3 years, the primary composite endpoint occurred in 6.6% vs 9.7%. Safety profiles were similar. This is the first randomized evidence that the lower target in the 2026 ACC/AHA dyslipidemia guideline is superior.

Calcium release channel deficiency syndrome in patients diagnosed with idiopathic ventricular fibrillation and decedents classified as sudden unexplained death in the young.

Calcium release channel deficiency syndrome (CRCDS), caused by loss-of-function RYR2 variants, can lead to ventricular fibrillation without exercise test abnormalities. This study assessed the prevalence of potentially CRCDS-causing variants in idiopathic ventricular fibrillation and unexplained sudden death in young individuals, underscoring the importance of genetic screening.

Deep endotyping of renal damage in type 2 diabetes

ex uno, plures

Kidney damage in type 2 diabetes is highly heterogeneous and poorly captured by traditional markers such as albuminuria and eGFR. This Kidney International review discusses how deep endotyping — integrating clinical trajectory analysis, renal histopathology, and molecular profiling — can identify subgroups with distinct pathophysiology, enabling more targeted therapy selection.

Kidney Disease

Improving Global Outcomes (KDIGO): navigating a rapidly changing landscape

KDIGO has published 17 kidney disease guidelines, but traditional full-revision cycles take years and lag behind rapidly evolving therapies such as SGLT2 inhibitors and finerenone. This article describes KDIGO's transition to modular, faster guideline updates to accelerate evidence translation into cardiometabolic clinical practice.

Optimizing NT-proBNP Inclusion Cut-offs for Randomized Clinical Trials in Heart Failure

Data from the Swedish Heart Failure Registry.

NT-proBNP is widely used as an enrolment criterion in heart-failure trials, but cut-offs vary widely. Using the Swedish Heart Failure Registry (SwedeHF, 43,750 patients), the investigators applied prior-trial cut-offs (200–5,000 pg/mL) and computed the 1-year incidence of cardiovascular death or heart-failure hospitalisation across subgroups (ejection fraction, care setting, AF, CKD, obesity). Higher cut-offs increased event enrichment but excluded more patients (more screening failures). In HFrEF outpatients, 1-year incidence rose from 22.0% (no cut-off) to 26.2% at ≥1,200 pg/mL, at the cost of 26% screening failure. The authors advise tailoring cut-offs to trial aims while accounting for obesity and CKD.

Left Atrial Appendage Closure or Medical Therapy in Atrial Fibrillation.

In the CLOSURE-AF trial, 912 patients with atrial fibrillation at high risk for both stroke and bleeding were randomized to catheter-based left atrial appendage closure or physician-directed best medical care. After a median follow-up of 3 years, LAA closure was not noninferior to medical therapy for the composite endpoint of stroke, systemic embolism, major bleeding, or cardiovascular death (16.8 vs 13.3 events per 100 patient-years; P=0.44 for noninferiority). Serious adverse events occurred in 82.5% of the device group versus 77.4% of the medical-therapy group. These results provide critical context for the CHAMPION-AF trial results to be presented at ACC.26.

Novel cardiovascular metabolic risk factor mechanisms and therapeutic opportunities.

This European Heart Journal review examines how metabolic disorders — obesity, type 2 diabetes, and dyslipidaemia — drive cardiovascular risk through newly identified mechanisms. The authors highlight unexpected cardiovascular benefits from metabolic drug classes including GLP-1 receptor agonists and SGLT2 inhibitors, and discuss emerging therapeutic opportunities at the intersection of metabolic and cardiovascular disease.

Senescent obesity signature in breast cancer

a paradigm of reverse cardio-oncology.

This EHJ review introduces 'reverse cardio-oncology': how cardiometabolic dysfunction — such as obesity — influences breast-cancer risk and biology through shared mechanisms (chronic inflammation, hormonal dysregulation, cellular senescence), even without overt cardiovascular disease. Refined obesity phenotypes (metabolically healthy/unhealthy, sarcopenic obesity) stratify risk better than BMI. Senescent adipose tissue is a key driver of the tumour microenvironment. Cardiometabolic therapies (GLP-1 agonists, SGLT2 inhibitors) and senolytics may offer shared targets for cardiovascular and oncologic prevention.

Gene Editing Therapy in Cardiovascular Disease

2026 ACC Scientific Statement: A Report of the American College of Cardiology

In this scientific statement the American College of Cardiology charts the rise of gene and base editing as a therapeutic strategy in cardiovascular disease. It places the rapid advances — such as permanently switching off PCSK9 — in a broader context and discusses the technology, the potential targets and the clinical, safety, regulatory and ethical questions that accompany these one-time, durable interventions. The international author panel includes Dutch researcher Menno Hoekstra (Leiden University).

Heritability and Cardiovascular Disease in Adult Offspring of Hypertensive Disorder of Pregnancy

A Systematic Review and Meta-Analysis

This systematic review and meta-analysis examined the heritability of hypertensive disorders of pregnancy (HDP) and their association with cardiovascular disease in adult offspring. Fifteen studies (266,244 participants, offspring aged 19-55) were pooled. Adults exposed in utero to HDP had higher systolic (+3.40 mmHg) and diastolic blood pressure (+2.19 mmHg) and more hypertension (OR 1.50). Female offspring had 72% higher odds of developing HDP themselves (OR 1.72) and 90% higher odds of preeclampsia (OR 1.90). Exposure to HDP and severe preeclampsia was also associated with more premature acute coronary syndrome and higher stroke risk. HDP heritability is thus high, and exposure is associated with hypertension, acute coronary syndrome and stroke in offspring — arguing for lifestyle advice, monitoring and prevention.

Managing glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors in clinical practice

The obesity epidemic has heightened the impact of cardiometabolic risk factors on cardiovascular and kidney disease. GLP-1 receptor agonists (GLP-1RAs) and SGLT2 inhibitors (SGLT2is), originally developed for type 2 diabetes, reduce cardiovascular and renal risk in randomised trials. SGLT2is are the first class proven to improve prognosis in heart failure with preserved ejection fraction (HFpEF), and evidence is accumulating that GLP-1RAs may also help there. Notably, the benefits are independent of diabetes status and baseline renal function. This practice-oriented review discusses how to use these drugs in everyday care for patients at high cardiovascular and renal risk, in line with evolving guidelines.

Role of Provocation and Exercise Imaging for the Identification of Candidates for Cardiac Myosin Inhibitors.

Left ventricular outflow tract obstruction (LVOTO) drives symptoms in obstructive hypertrophic cardiomyopathy (oHCM). Some patients show treatment-qualifying obstruction only during exercise echocardiography. In this single-centre retrospective cohort (56 symptomatic oHCM patients on mavacamten), 42.9% qualified exclusively during exercise echo. These patients did not have milder disease: functional limitation and exercise capacity were similar to those qualifying at rest or with Valsalva. By 24 weeks, both groups similarly achieved a non-obstructive gradient (<30 mmHg) and NYHA improvement. Exercise echocardiography thus identifies a substantial group of treatable oHCM patients missed by resting assessment.

Triglyceride-glucose index and mortality in critically ill patients with cardiovascular-kidney-metabolic syndrome stage 4.

The triglyceride-glucose (TyG) index is a surrogate marker of insulin resistance. In early stages of cardiovascular-kidney-metabolic (CKM) syndrome a higher TyG index is linked to more events, but its value in critically ill patients with CKM stage 4 was unclear. In this retrospective study from the MIMIC-IV database (3,125 ICU patients with CKM-4), 1-year mortality was 34%. Each standard-deviation higher TyG index was associated with 23% higher mortality (HR 1.23), and the highest tertile had 30% higher risk than the lowest (HR 1.30), with a linear relationship. The TyG index may serve as a simple marker for risk stratification in this group, though prospective studies must confirm its clinical value.

Systemic Inflammation and Recurrence After Atrial Fibrillation-Related Stroke

An Individual Participant Data Meta-Analysis.

This individual participant data meta-analysis showed that systemic inflammatory markers (IL-6 and hsCRP) predict recurrent vascular events after AF-related stroke, irrespective of AF status. The findings support including AF patients in future trials of anti-inflammatory therapy for secondary stroke prevention.

Lifetime Adverse Pregnancy Outcome History and Cardiovascular Risk

How multiple types of adverse pregnancy outcomes (APOs) across reproductive life jointly affect long-term cardiovascular risk is little studied. In 59,154 parous women from the Nurses' Health Study II, lifetime history of gestational diabetes, gestational hypertension, preeclampsia, preterm delivery and low birth weight was self-reported and linked to cardiovascular events. Each APO was associated with higher cardiovascular risk, but after accounting for co-occurrence of multiple APOs, only gestational hypertension (HR 1.62) and preeclampsia (HR 1.31) retained independent associations. Later development of hypertension, diabetes and hypercholesterolaemia explained much (58%) of the association. Adding APOs to established risk factors improved prediction only modestly. APOs — especially gestational hypertension and preeclampsia — thus flag higher future risk, largely via subsequent risk factors.

Real-world evidence with dapagliflozin in heart failure with reduced ejection fraction in Central Eastern Europe and the Baltic region (EVOLUTION-HF CEE-BA Study).

SGLT2 inhibitors are one of the four pillars of heart failure with reduced ejection fraction (HFrEF) treatment. After dapagliflozin's 2020 approval, real-world data are relevant for clinicians and payers. EVOLUTION-HF CEE-BA is an observational, longitudinal study across 102 centres in nine Central/Eastern European and Baltic countries that characterised the population started on dapagliflozin for HFrEF in routine practice (1,131 patients; ischaemic aetiology in 52%). All treatment decisions were at the provider's discretion per local practice. The study thus maps the use and course of dapagliflozin for HFrEF in Central/Eastern European practice.

Use of Coronary Artery Calcium Scoring in Individuals With Elevated Lipoprotein(a)

A Multicohort Study

This multicohort study demonstrated that coronary artery calcium scoring remains a useful ASCVD risk assessment tool in individuals with elevated lipoprotein(a). CAC provides incremental risk stratification even when Lp(a) is elevated, supporting its use in Lp(a)-enriched populations.

2026 ACC/AHA Guideline on the Management of Dyslipidemia

A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines

The 2026 ACC/AHA dyslipidemia guideline introduces a universal LDL-cholesterol target of <100 mg/dL for primary prevention and <55 mg/dL for very-high-risk secondary prevention. The guideline endorses earlier initiation of lipid-lowering therapy, Lp(a) measurement, and expanded indications for PCSK9 inhibitors and inclisiran.

Off-label underdosing of edoxaban antithrombotic therapy for patients with atrial fibrillation and stable coronary artery disease

findings from the EPIC-CAD trial.

This study documented the adverse consequences of off-label edoxaban underdosing in AF patients, showing increased thrombotic risk without meaningful bleeding reduction, reinforcing adherence to approved dosing criteria.

Differences in Disease Trajectory, Comorbidities, and Mortality in Sarcomeric and Nonsarcomeric Hypertrophic Cardiomyopathy

Sarcomere variants are a major cause of hypertrophic cardiomyopathy (HCM) and are associated with worse prognosis. In this longitudinal multicentre study from the SHaRe registry (6,120 genotyped HCM patients, 50% sarcomeric, median follow-up 5.3 years), the influence of genetic classification and comorbidities on disease trajectory, event timing and causes of death was examined. Sarcomeric HCM was diagnosed at a younger age (median 38.1 vs 54.3 years) and more often in women. Using time-varying models, the study maps the sequence of cardiovascular events to better inform prognosis and treatment in sarcomeric versus nonsarcomeric HCM.

Semaglutide promotes bone marrow-derived progenitor cell flux towards an anti-inflammatory and pro-regenerative profile in high-risk patients

the SEMA-VR CardioLink-15 trial.

This translational study showed that semaglutide mobilizes anti-inflammatory and pro-regenerative progenitor cells from the bone marrow, providing a novel mechanistic explanation for the cardiovascular benefit of GLP-1 receptor agonists.

Effect of baxdrostat on ambulatory blood pressure in patients with resistant hypertension (Bax24)

a phase 3, randomised, double-blind, placebo-controlled trial

The phase 3 Bax24 trial demonstrated that baxdrostat, an aldosterone synthase inhibitor, significantly reduced 24-hour ambulatory systolic blood pressure compared with placebo in patients with resistant hypertension. The results advance aldosterone synthase inhibition as a promising new drug class for treatment-resistant blood pressure.

Atrial fibrillation

This comprehensive Lancet Seminar provides a state-of-the-art overview of atrial fibrillation, covering its rising global prevalence of 37.6 million affected individuals, the impact of wearable device-based detection, contemporary management strategies including early rhythm control and pulsed field ablation, and integrated AF care pathways.

Effect of baxdrostat on ambulatory blood pressure in patients with resistant hypertension (Bax24)

a phase 3, randomised, double-blind, placebo-controlled trial.

The Bax24 phase 3 trial confirmed that baxdrostat significantly reduces ambulatory blood pressure in patients with resistant hypertension. The results replicate the earlier phase 2 findings and advance aldosterone synthase inhibition toward clinical implementation.

Kidney disease and heart failure

recent advances and current challenges: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

This KDIGO consensus conference summary addressed the intersection of heart failure and chronic kidney disease, reviewing advances in cardiorenal understanding and the challenges of managing patients with both conditions, including the role of SGLT2 inhibitors and finerenone.

Direct-acting oral anticoagulant or vitamin K antagonist for the frail elderly patient with atrial fibrillation

does one size fit all?

This EHJ editorial discussed the choice between DOACs and vitamin K antagonists for frail elderly AF patients, reviewing the emerging evidence supporting safe transition to NOACs even in the most vulnerable anticoagulation population.

Semaglutide in peripheral artery disease and diabetes by baseline disease severity and age

the STRIDE trial.

This EHJ article presented STRIDE trial subanalyses of semaglutide in patients with peripheral artery disease and diabetes stratified by baseline disease severity and age, informing the use of GLP-1 agonists in the PAD population.

Oral PCSK9 inhibitor enlicitide lowers LDL cholesterol levels in phase 2 trial.

This phase 2 trial of enlicitide, an oral PCSK9 inhibitor, showed significant LDL cholesterol reduction. As the first oral PCSK9 inhibitor in clinical development, enlicitide could dramatically expand access to advanced lipid-lowering therapy.

Finerenone in Type 1 Diabetes and Chronic Kidney Disease.

This NEJM phase 3 trial demonstrated that finerenone improved kidney outcomes in patients with type 1 diabetes and chronic kidney disease, extending the benefit of nonsteroidal mineralocorticoid receptor antagonism beyond the type 2 diabetes population. The results address a previously unmet therapeutic need in type 1 diabetes nephropathy.

Interplay of Age and Sex With Clinic and Ambulatory Blood Pressure and Mortality

This analysis from the Spanish ABPM registry explored the interplay between age, sex, clinic and ambulatory blood pressure values, and cardiovascular mortality, providing insights into sex-specific blood pressure targets.

Finerenone for Diabetic Kidney Disease in Type 1 Diabetes — A Fine Answer?

This NEJM editorial discussed the implications of finerenone for diabetic kidney disease in type 1 diabetes, evaluating whether the cardiorenal benefit extends beyond the type 2 diabetes population.

Aspirin after PCI in Acute Coronary Syndromes

This NEJM article evaluated the role of aspirin after PCI in acute coronary syndromes in light of contemporary de-escalation evidence from TWILIGHT, T-PASS, and STOPDAPT trials, addressing the shifting paradigm toward aspirin-free antiplatelet strategies.

Blood-Pressure Targets in Hypertension Management

This NEJM article discussed optimal blood pressure targets in hypertension management, reviewing the evidence from SPRINT, STEP, and ESPRIT that supports lower targets while addressing the clinical challenges of implementing aggressive blood pressure control.

Invasive haemodynamic validation of an artificial intelligence echocardiographic tool for detecting heart failure with preserved ejection fraction.

An FDA-approved AI tool detects heart failure with preserved ejection fraction (HFpEF) from echocardiographic images (apical 4-chamber), without other clinical data. In this external validation (47 patients with unexplained dyspnoea who underwent both echo and right heart catheterisation), the tool was compared with the invasive standard (wedge pressure ≥15 mmHg at rest or ≥25 mmHg with exercise). The AI had high specificity (88%) and positive predictive value (86%) but low sensitivity (30%); using the PCWP/cardiac-output slope, specificity and PPV reached 100%. AI-positive patients had higher filling pressures and pulmonary resistance. Among patients with indeterminate H2FPEF scores, the AI identified 80% of invasively confirmed HFpEF. The tool is thus best for identifying patients with clearly abnormal haemodynamics, not for ruling out HFpEF.

Quantifying skeletal muscle energy metabolism during exercise in heart failure with preserved ejection fraction using in vivo  31P magnetic resonance spectroscopy.

Patients with heart failure and preserved ejection fraction (HFpEF) have markedly reduced exercise capacity with poorly understood, multifactorial causes. In this Dutch two-site study (58 HFpEF patients, 16 controls), in-vivo 31phosphorus MR spectroscopy measured mitochondrial oxidative muscle metabolism via phosphocreatine recovery after isometric or dynamic exercise. Phosphocreatine recovery halftime after isometric exercise was prolonged in HFpEF patients (27 vs 24 seconds), indicating reduced skeletal-muscle oxidative capacity. This held regardless of iron deficiency, whereas higher hs-CRP was associated with slower recovery. Exercise intolerance in HFpEF thus arises partly from intrinsically impaired muscle energetics, not iron deficiency alone.

In vivo base editing gene therapy for heterozygous familial hypercholesterolemia

a phase 1 trial.

YOLT-101 is an in vivo gene therapy that uses adenine base editing — delivered via GalNAc-modified lipid nanoparticles — to inactivate PCSK9 for durable LDL lowering. In this ongoing phase 1 trial, six adults with heterozygous familial hypercholesterolaemia and uncontrolled LDL received a single ascending dose (0.2–0.6 mg/kg). No grade ≥3 adverse events occurred; transient infusion reactions and liver-enzyme elevations were most common. A single infusion produced dose-dependent, durable reductions: at the highest dose (0.6 mg/kg) PCSK9 and LDL cholesterol fell by 74.4% and 52.3% respectively at 24 weeks. Alongside VERVE-102, this is a second base-editing programme pursuing one-time, durable PCSK9 knockdown.

Worse risk profile, number of grafts and hospital death but acceptable late survival in females undergoing coronary surgery

a 20-year propensity matched analysis

This study examined sex differences in isolated coronary artery bypass grafting (CABG) over 20 years (2001-2021) at a single centre, with 1:1 propensity score matching (2,573 women vs 2,573 men). Women were older and more often had class III-IV angina, hypertension and diabetes. After matching, women received fewer left internal mammary artery (LIMA) grafts (84% vs 88%) and fewer total grafts (median 2 vs 3), had higher in-hospital mortality (2.2% vs 1.3%; OR 1.74) and longer hospital stays. Twenty-year survival, however, was similar. Off-pump CABG lowered in-hospital mortality in women (1.6% off-pump vs 3.0% on-pump). Women thus have higher perioperative risk and receive fewer (arterial) grafts, while long-term survival is equal — arguing for a female-tailored perioperative approach.

2026 Acute Pulmonary Embolism Guideline-at-a-Glance

This JACC guideline-at-a-glance provides a concise visual summary of the 2026 acute pulmonary embolism guideline, distilling the key recommendations into an accessible reference format for rapid clinical decision-making.

Cardiac Screening for Conditions Associated With Sudden Cardiac Death

Yield, Interventions, and SCA/SCD Incidence in 104,369 Young Individuals

This large-scale screening study of over 104,000 young individuals for conditions associated with sudden cardiac death evaluated the diagnostic yield, interventions triggered, and subsequent incidence of sudden cardiac arrest, informing the ongoing debate about population-level cardiac screening.

Cardiac Screening in the Young

Time to Sound the Battle CRY?

This JACC commentary discussed the implications of the CRY cardiac screening study in young individuals, debating the value and limitations of population-level cardiac screening programs for sudden cardiac death prevention.

Comparison of the European Society of Cardiology 0/1-Hour and High-Sensitivity Troponin in the Evaluation of Patients With Suspected Acute Coronary Syndrome 0/2-or-0/3-Hour Algorithms for Rapid Myocardial Infarction Diagnosis

A Prospective Multicenter Study

This prospective multicenter study compared the diagnostic accuracy of the ESC 0/1-hour high-sensitivity troponin algorithm with standard evaluation for patients presenting with suspected acute coronary syndromes, assessing real-world performance of the rapid rule-out/rule-in protocol.

Effect of Baduanjin on Blood Pressure Among Individuals With High-Normal Blood Pressure

A Multicenter, Open-Label, Blinded-Outcome Randomized Controlled Trial

This multicenter randomized trial evaluated Baduanjin, a traditional Chinese exercise form, for blood pressure reduction in individuals with high-normal blood pressure, testing a culturally appropriate lifestyle intervention for hypertension prevention.

High-Dose Influenza Vaccination in Atherosclerotic Cardiovascular Disease

A Multinational Pooled Analysis of DANFLU-2 and GALFLU (FLUNITY-HD)

This multinational pooled analysis of the DANFLU-2 and GALFLU trials evaluated the effect of high-dose versus standard-dose influenza vaccination on cardiovascular outcomes in patients with atherosclerotic cardiovascular disease, addressing whether enhanced immunogenicity translates to better cardiovascular protection.

Impact of Early, Delayed, or Interrupted Treatment in Children With Familial Hypercholesterolemia

This study examined the long-term cardiovascular effects of early, delayed, or interrupted lipid-lowering treatment in children with familial hypercholesterolemia, providing evidence for the importance of early and continuous treatment initiation.

Six-Year Outcomes After Transcatheter vs Surgical Aortic Valve Replacement in Low-Risk Patients With Aortic Stenosis

Six-year outcomes from the comparison of transcatheter versus surgical aortic valve replacement in low-risk patients with aortic stenosis demonstrated sustained comparable results, providing long-term reassurance about TAVR durability in this population.

Some Much-Needed CONFIDENCE to Combat the Risk-Treatment Paradox in Chronic Kidney Disease

This JACC commentary discussed the risk-treatment paradox in chronic kidney disease, where patients at highest cardiovascular risk are least likely to receive evidence-based therapies including SGLT2 inhibitors and statins.

Timing of Cardiovascular and Kidney Benefits With Finerenone in Heart Failure and Chronic Kidney Disease With Type 2 Diabetes

This JACC analysis examined the time course of cardiovascular and kidney benefits with finerenone in patients with heart failure and chronic kidney disease with type 2 diabetes, characterizing how quickly the cardiorenal protection emerges after treatment initiation.

journal club

This Journal Club discussed the clinical implications of the VALIANT trial results from the New England Journal of Medicine, addressing contemporary treatment approaches in nephrology.

Abelacimab vs Rivaroxaban in Older Individuals With Atrial Fibrillation

A Prespecified Analysis of the Phase 2b AZALEA-TIMI 71 Trial.

This AZALEA-TIMI 71 subanalysis confirmed that abelacimab provides less bleeding than rivaroxaban in older AF patients, the population at highest bleeding risk with conventional anticoagulants.

Heart failure in the elderly

epidemiology, mechanisms, and management.

This European Heart Journal review describes the epidemiology, pathophysiology, and management of heart failure in the elderly, highlighting that the lifetime risk exceeds 25% after age 70. The article addresses the challenges of polypharmacy, frailty, and comorbidity that complicate guideline-directed therapy in older patients.

Additive Cardiorenal Benefits of Finerenone and SGLT2 Inhibitor Combination Therapy in Diabetic CKD

A Propensity-Matched Real-World Study.

This real-world propensity-matched study showed that combining finerenone with SGLT2 inhibitors provides additive cardiorenal benefits in diabetic CKD compared with SGLT2 inhibitor monotherapy, supporting dual neurohormonal and metabolic protection.

SGLT2 inhibition in Patients with Type 2 Diabetes and CKD Experiencing a Deterioration in Estimated Glomerular Filtration Rate to <20ml/min/1.73m

This post-hoc CREDENCE analysis showed that SGLT2 inhibition remains safe and effective when eGFR declines below 20 mL/min, supporting continuation of therapy in patients with severely reduced kidney function rather than discontinuation at an arbitrary eGFR threshold.

Switching from warfarin to direct oral anticoagulants in frail elderly Asian patients with atrial fibrillation

a Korean nationwide study.

This Korean nationwide study showed that switching from well-managed warfarin to DOACs in frail elderly patients with atrial fibrillation was associated with similar or improved outcomes. The real-world evidence supports transitioning to DOACs even in the oldest and most vulnerable AF population.

Carotid plaque macrophage burden and inflammatory lipid-associated macrophage markers predict secondary major adverse cardiovascular events after endarterectomy.

This European Heart Journal study demonstrated that carotid plaque macrophage burden and inflammatory lipid-associated macrophage markers independently predict secondary major adverse cardiovascular events beyond traditional risk factors. The findings link plaque inflammation at the cellular level to recurrent cardiovascular risk.

Intensive BP Control and Cognitive Function

A Randomized Clinical Trial

This randomized trial investigated whether intensive blood pressure control preserves cognitive function in an East Asian population, addressing the uncertainty about aggressive BP targets and brain health in this demographic.

Low-Dose Rivaroxaban to Prevent Left Ventricular Thrombosis After Anterior Myocardial Infarction

The APERITIF Randomized Clinical Trial.

The APERITIF randomized trial investigated whether adding low-dose rivaroxaban to dual antiplatelet therapy prevents left ventricular thrombus formation after anterior acute myocardial infarction.

Combined associations of GLP-1 receptor agonists and a healthy lifestyle with cardiovascular outcomes among individuals with type 2 diabetes

a prospective cohort study.

This prospective cohort study in Lancet Diabetes & Endocrinology examined the combined effects of GLP-1 receptor agonists and eight healthy lifestyle factors on cardiovascular outcomes. The findings demonstrate additive benefit, with the combination of pharmacotherapy and healthy lifestyle conferring the greatest cardiovascular risk reduction.

Forecasting the Burden of Cardiovascular Disease and Stroke in Women in the United States Through 2050

A Scientific Statement From the American Heart Association

This AHA scientific statement provided forecasts for cardiovascular disease and stroke prevalence in women through 2050, highlighting projected increases driven by aging, obesity, and diabetes, and informing prevention strategies targeting women's cardiovascular health.

Outcomes of heart failure with reduced, mildly reduced, or preserved ejection fraction

the ESC HF III registry.

The ESC Heart Failure III Registry followed 10,162 patients across 41 countries with HFrEF, HFmrEF, and HFpEF, providing contemporary real-world data on in-hospital and 1-year outcomes across the heart failure spectrum in routine clinical practice.

Systemic Embolic Events in Atrial Fibrillation

An Individual Patient Data Meta-analysis of 71 683 Participants Randomized to NOAC Versus Warfarin.

This individual patient data meta-analysis of over 71,000 AF patients characterized systemic embolic events, showing that NOACs effectively prevent both stroke and non-cerebral embolism compared with warfarin.

Malnutrition and Cachexia in Inpatients With Acute Cardiac Conditions

A Scientific Statement From the American Heart Association

This AHA scientific statement addressed malnutrition and cachexia in patients with acute cardiovascular conditions beyond heart failure, covering assessment, management, and the impact of nutritional status on clinical outcomes across the spectrum of acute cardiac disease.

Risk of Heart Failure Hospitalization for GLP-1 Receptor Agonists Versus DPP-4 Inhibitors or SGLT-2 Inhibitors in Patients With Type 2 Diabetes

A Target Trial Emulation

This target trial emulation using Swedish population data compared GLP-1 receptor agonists with DPP-4 inhibitors and SGLT2 inhibitors for heart failure hospitalization risk in type 2 diabetes, providing real-world comparative effectiveness data for cardiometabolic drug selection.

Accelerometry-defined physical activity and quality of life in hypertrophic cardiomyopathy

This study used accelerometry to objectively measure physical activity in HCM patients, showing that reduced activity levels are associated with worse quality of life and challenging the assumption that exercise restriction improves safety.

Effect of semaglutide on COVID-19 and other infections

an analysis from the FLOW randomized clinical trial.

This FLOW trial analysis showed that semaglutide reduces the risk of COVID-19 and other infections in patients with type 2 diabetes and CKD, demonstrating an unexpected anti-infectious benefit of GLP-1 receptor agonism.

Mitigating Risk of Kidney Dysfunction After Heart Transplantation and Therapeutic Approaches.

This Circulation Heart Failure review addressed strategies for mitigating kidney dysfunction after heart transplantation, covering recipient risk factors, perioperative management, and therapeutic approaches to preserve renal function.

Diabetes Increases the Risk of Heart Failure in Myocarditis

A Propensity-Matched Nationwide Database Analysis.

This US nationwide database analysis showed that diabetes significantly increases the risk of heart failure in patients hospitalized with myocarditis, highlighting the adverse interaction between metabolic disease and myocardial inflammation.

Primary care Adherence To Heart failure guidelines in post-Discharge, Evaluation & Routine management (PATHFINDER)

a randomised controlled trial.

The PATHFINDER trial tested a combined intervention of inpatient education, a discharge plan with cardiac rehabilitation referral, and primary care support for heart failure, evaluating implementation strategies for guideline adherence.

The year in cardiovascular medicine 2025

the top 10 papers in ischaemic heart disease.

This European Heart Journal annual review highlighted the top 10 papers of 2025 in ischemic heart disease, providing an expert-curated summary of the most impactful developments in coronary artery disease research.

Immunoadsorption in dilated cardiomyopathy

the IASO-DCM trial.

The IASO-DCM trial investigated immunoadsorption as a treatment for dilated cardiomyopathy with cardiac autoantibodies, exploring a novel immunomodulatory approach to this form of heart failure.

Cost-effectiveness of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists for patients with high cardiovascular risk and type 2 diabetes in Canada.

This Canadian simulation study compared the cost-effectiveness of SGLT2 inhibitors versus GLP-1 receptor agonists in type 2 diabetes with high cardiovascular risk, informing formulary and reimbursement decisions for cardiometabolic therapy.

Pelacarsen and lipoprotein(a) apheresis in secondary prevention

the Lp(a)FRONTIERS APHERESIS trial.

The Lp(a)FRONTIERS APHERESIS trial investigated whether pelacarsen can reduce the need for lipoprotein apheresis in patients with elevated Lp(a) and established cardiovascular disease. The study addresses a critical question about the potential of pharmacological Lp(a) lowering to replace this burdensome procedure.

Enhanced cardiovascular disease risk prediction using integrated machine learning models

a study from the UK Biobank cohort

Classical risk scores such as Framingham and SCORE sometimes fall short due to their limited variable set. In this study, machine learning was used to develop a comprehensive cardiovascular risk model from the UK Biobank (240,644 participants), combining genetic scores, clinical parameters and lifestyle factors, with separate models for overall cardiovascular risk, cerebrovascular and thrombotic disease. The integrated model (clinical + lifestyle + genetic) performed best, with an AUC of 0.85 — an improvement of 0.12 over the Framingham score. Models based on clinical, lifestyle or genetic data alone performed worse. Key predictors were age, systolic blood pressure, cystatin C and waist circumference. Combining clinical, lifestyle and genetic data thus substantially improves cardiovascular risk prediction — though validation in diverse populations is still needed.

Cardiovascular-Kidney-Metabolic Interplay in Patients with Atrial Fibrillation Receiving Direct Oral Anticoagulants.

This comprehensive review examined the cardiovascular-kidney-metabolic interplay in AF patients on DOACs, exploring how CKM syndrome affects anticoagulation efficacy, safety, and dosing decisions.

Transcatheter or Surgical Aortic-Valve Replacement in Low-Risk Patients at 7 Years.

The 7-year PARTNER 3 results confirmed comparable outcomes between TAVR and surgical aortic valve replacement in low-risk patients, with maintained valve durability and no excess structural deterioration. These are the longest-term data supporting TAVR across the full surgical risk spectrum.

Conduction disturbances after transcatheter aortic valve implantation.

This European Heart Journal review addressed conduction disturbances after TAVI, covering the predictors of permanent pacemaker implantation, the impact on long-term outcomes, and strategies for minimizing conduction complications during transcatheter valve procedures.

Secondary Prevention after Ischemic Stroke.

This NEJM review provided a comprehensive update on secondary prevention after ischemic stroke, covering modifiable risk factors, mechanism-specific therapies, and contemporary evidence on anticoagulation, antiplatelet therapy, and lipid lowering for recurrent stroke prevention.

2026 AHA/ACC Guideline for the Evaluation and Management of Acute Pulmonary Embolism in Adults

A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines

The 2026 AHA/ACC multisociety guideline provides comprehensive, de novo recommendations for the evaluation and management of acute pulmonary embolism in adults, covering risk stratification, anticoagulation, thrombolysis, catheter-directed therapy, and long-term follow-up.

Beta-Blockers after Myocardial Infarction

This NEJM review article synthesizes the current evidence on beta-blocker use after myocardial infarction, reflecting the paradigm shift from routine long-term therapy to an evidence-based approach where beta-blockers are no longer mandatory when ejection fraction is preserved.

Gene Therapy for Nephropathic Cystinosis

This NEJM article discussed gene therapy as a treatment option for nephropathic cystinosis, a rare lysosomal storage disorder affecting kidney function, exploring the potential for curative genetic intervention.

Albuminuria or proteinuria in glomerular disease and CKD - which one to use?

This NDT discussion addressed the clinical question of whether albuminuria or proteinuria is the preferred measurement in glomerular disease and CKD, informing the standardization of kidney disease monitoring.

Novel Plasma Proteomic Markers and Risk of Venous Thromboembolism

This Circulation study used large-scale, high-throughput proteomics to identify novel plasma protein markers associated with venous thromboembolism risk, advancing the molecular understanding of VTE pathogenesis.

Early versus late anticoagulation treatment after acute ischemic stroke with atrial fibrillation

a meta-analysis of randomized controlled trials.

This meta-analysis of randomized trials compared early versus late anticoagulation initiation after acute ischemic stroke in AF patients, providing the pooled evidence to guide the timing of DOAC start after cerebrovascular events.

Use of kidney-preserving medications in breastfeeding

This Kidney International review addressed the safety of kidney-preserving medications during breastfeeding, providing practical guidance for CKD women on which cardiovascular and renal therapies are compatible with lactation.

Prognostic utility of stress perfusion cardiac magnetic resonance in patients with known or suspected coronary artery disease and inconclusive exercise stress testing

Exercise stress testing (EST) is widely used for risk stratification in coronary artery disease (CAD) but yields inconclusive results in up to 20%. Stress perfusion CMR is an accurate alternative, but data after inconclusive EST were limited. In this study (414 patients with known or suspected CAD and inconclusive EST referred for stress CMR, 2009-2022), major adverse cardiovascular events (MACE) were examined. Over a median 6.9-year follow-up, 7.7% had a MACE. Patients with inducible ischaemia on CMR had a much higher annual MACE rate (2.8 vs 0.8 per 100 patient-years). Inducible ischaemia was an independent predictor of MACE (HR 4.03), alongside atrial fibrillation and resting systolic blood pressure. Stress perfusion CMR thus provides valuable prognostic information and effectively stratifies risk in patients with an inconclusive exercise test.

Prospective Associations of Obesity and Obesity Severity With 9 Cardiovascular Outcomes

The Cross-Cohort Collaboration

This prospective cross-cohort analysis showed that not only obesity but particularly its severity is strongly predictive of multiple cardiovascular outcomes, with a graded relationship across the full BMI spectrum.

Aspirin dosing after acute coronary syndrome with suspected aspirin resistance

the ANDAMAN trial.

The ANDAMAN trial tested higher aspirin dosing in ACS patients with suspected aspirin resistance, evaluating whether dose escalation overcomes inadequate platelet inhibition in diabetes and high-risk patients.

Improving outcomes of atrial fibrillation ablation by integrated personalized lifestyle interventions

a randomized controlled trial.

This randomized trial confirmed that integrated personalized lifestyle interventions (weight management, fitness, sleep optimization, alcohol reduction) significantly improve catheter ablation outcomes for atrial fibrillation.

Vericiguat and mortality in heart failure and reduced ejection fraction

the VICTOR trial.

The VICTOR trial analysis confirmed that vericiguat reduces mortality in patients with HFrEF and recent decompensation. The mortality benefit adds to the heart failure event reduction shown in VICTORIA, strengthening vericiguat's position in guideline-directed therapy.

Criteria to Assess the Predictive and Clinical Utility of Novel Models, Biomarkers, and Tools for Risk of Cardiovascular Disease

A Scientific Statement From the American Heart Association

This AHA scientific statement described criteria for assessing the predictive and clinical utility of novel cardiovascular risk models, biomarkers, and tools, providing a methodological framework for evaluating new risk assessment technologies.

Renal and urothelial cancer risks with SGLT2 inhibitors vs GLP-1 receptor agonists in type 2 diabetes

a target trial emulation.

This target trial emulation compared renal and urothelial cancer risks between SGLT2 inhibitors and GLP-1 receptor agonists in type 2 diabetes, addressing an important safety question for these widely prescribed cardiometabolic agents.

New drug therapies for hypertension

This Lancet review described new drug therapies for hypertension targeting novel physiological pathways including aldosterone synthase inhibition, endothelin antagonism, and RNA interference-based angiotensinogen silencing, addressing the unmet need for patients with resistant blood pressure.

Transthyretin Cardiac Amyloidosis Evaluation and Management

2025 ACC Concise Clinical Guidance.

This 2025 ACC clinical guidance for transthyretin amyloid cardiomyopathy provides structured recommendations for diagnosis, risk stratification, and treatment including tafamidis. The document addresses the growing recognition and improved detection of this previously underdiagnosed condition.

Clonal Hematopoiesis and Its Cardiovascular Implications

A Scientific Statement From the American Heart Association

This AHA scientific statement reviewed the emerging evidence on clonal hematopoiesis and its cardiovascular implications, describing how somatic mutations in hematopoietic stem cells drive inflammation and increase cardiovascular risk independent of traditional risk factors.

Spontaneous Myocardial Infarction After Left Main Revascularization

The EXCEL Trial

This EXCEL analysis compared rates and prognostic implications of spontaneous MI after PCI versus CABG for left main disease, providing granular data on the long-term ischemic risk profile of each revascularization strategy.

Coronary Atherosclerosis in Patients With Cancer and Survivors

A Scientific Statement From the American Heart Association

This AHA scientific statement addressed the emerging convergence between atherosclerotic cardiovascular disease and cancer, driven by shared risk factors, overlapping pathophysiology, and the cardiovascular toxicity of cancer therapies.

Glucagon-like Peptide Receptor Agonists and Kidney Outcomes in the Era of Personalized Medicine

Focus on Albuminuria.

This review assessed the renoprotective effects of GLP-1 receptor agonists with specific focus on albuminuria reduction, positioning these agents as important kidney-protective therapies alongside SGLT2 inhibitors in the personalized medicine era.

Insulin Resistance Compromises the Pentose Phosphate Pathway and Impairs Left Ventricular Assist Device–Mediated Myocardial Recovery in Obese Patients with Heart Failure

This study demonstrated that insulin resistance compromises the pentose phosphate pathway and impairs LVAD-mediated cardiac recovery, explaining why diabetic patients have worse myocardial recovery during mechanical support.

The Aldehyde Dehydrogenase 2 rs671 Variant Enhances Platelet Activation and Arterial Thrombosis

This study showed that the ALDH2 rs671 variant, present in 30-50% of East Asians, enhances platelet activation and arterial thrombosis, explaining the increased MI risk in carriers of this common genetic polymorphism.

The Inherited Basis of Coronary Artery Disease.

This NEJM review summarises how genetic research has reshaped the understanding, treatment, prevention and risk prediction of coronary artery disease. Monogenic causes occur in roughly 1 in 250 people and usually produce markedly elevated lipid levels. At the population level, hundreds of common small-effect variants together have even greater influence; combined into a polygenic risk score (PRS), risk in the top 5% is 3–5 times the average. The PRS can multiply the absolute risk from clinical scores. Questions about clinical value, cost-effectiveness and implementation remain.

A Placebo-Controlled Trial of the Oral PCSK9 Inhibitor Enlicitide.

Enlicitide decanoate, an oral PCSK9 inhibitor, was tested in this multinational double-blind, placebo-controlled trial in 2,909 adults with established atherosclerotic cardiovascular disease (LDL ≥55 mg/dL) or at risk of a first event (LDL ≥70 mg/dL). Participants received daily enlicitide 20 mg or placebo (2:1) for 52 weeks. At week 24, LDL cholesterol fell by a mean of 57.1% with enlicitide versus +3.0% with placebo — a difference of almost 56 percentage points. Oral PCSK9 inhibition thus approaches the efficacy of the injectable agents, with potential to greatly improve access and adherence.

Efimosfermin alfa (BOS-580) once per month in people with metabolic dysfunction-associated steatohepatitis with F2 or F3 fibrosis

results from a 24-week, randomised, double-blind, placebo-controlled, phase 2 trial

This phase 2 trial of efimosfermin alfa (FGF21 analogue) showed favorable tolerability in patients with MASH and F2/F3 fibrosis. The results support further development of metabolic therapies targeting the liver-cardiovascular axis.

Intravenous tenecteplase for acute ischaemic stroke within 24 h due to basilar artery occlusion

This Lancet publication addresses basilar artery occlusion, the most severe presentation of large-vessel ischemic stroke, with new randomized and observational evidence supporting intravenous tenecteplase therapy within an extended 24-hour treatment window.

Tenecteplase versus standard medical treatment for basilar artery occlusion within 24 h (TRACE-5)

a multicentre, prospective, randomised, open-label, blinded-endpoint, superiority, phase 3 trial

The TRACE-5 trial demonstrated that intravenous tenecteplase within 24 hours improved functional outcomes in Chinese patients with ischemic stroke due to basilar artery occlusion. The results support thrombolysis as an effective treatment for this devastating posterior circulation stroke subtype.

Physical activity and risk of adverse events in atrial fibrillation

evidence from European and Asian cohorts.

This post-hoc analysis of European and Asian-Pacific AF registries showed that physical activity levels are associated with different clinical characteristics and outcomes in AF patients, supporting exercise recommendations across diverse populations.

Semaglutide as adjunctive therapy to catheter ablation in obesity-related paroxysmal atrial fibrillation.

This study evaluated semaglutide as adjunctive therapy to catheter ablation in obese patients with paroxysmal AF, testing whether GLP-1 receptor agonist-mediated weight loss improves ablation outcomes in obesity-related arrhythmia.

Contemporary management of atrial fibrillation in patients with cancer-the 2025 European Heart Rhythm Association survey.

This 2025 EHRA position paper addressed the contemporary management of AF in patients with cancer, providing practical guidance for the complex decisions around anticoagulation, rate/rhythm control, and drug interactions in this dual-disease population.

Semaglutide vs tirzepatide in patients with obesity and HFpEF

a report from a global federated research network.

This federated research network analysis provided the first direct comparison of semaglutide versus tirzepatide in patients with obesity and HFpEF, comparing real-world outcomes of these two leading incretin therapies.

Dapagliflozin to Reduce Early Recurrence After Catheter Ablation for Atrial Fibrillation

The DARE-AF Randomized Clinical Trial.

The DARE-AF trial demonstrated that dapagliflozin reduces early AF recurrence after catheter ablation. The finding suggests that SGLT2 inhibitors may have antiarrhythmic properties that complement ablation therapy.

SGLT2 Inhibitor Use and Cardiorenal Outcomes in Type 2 Diabetes With Liver Cirrhosis.

This study evaluated SGLT2 inhibitor use and cardiorenal outcomes in patients with both type 2 diabetes and liver cirrhosis, providing safety and efficacy data for this high-risk and typically excluded population.

Cardiovascular-Kidney Effects of Dapagliflozin in Patients at Cardiovascular Risk With or Without Type 2 Diabetes

Results of a Randomized, Double-Blind, Placebo-Controlled Trial.

This study demonstrated that dapagliflozin improves vascular stiffness and cardiorenal markers in patients at cardiovascular risk regardless of diabetes status, providing mechanistic support for the universal cardiorenal protective effects of SGLT2 inhibitors.

CagriSema Reduces Blood Pressure in Adults With Overweight or Obesity

REDEFINE 1.

The REDEFINE 1 analysis showed that CagriSema (cagrilintide plus semaglutide) significantly reduces blood pressure in adults with overweight or obesity, with the antihypertensive effect adding to the metabolic and weight-loss benefits.

Outcomes After Switching Cardiac Troponin Assays in ACS

This interrupted time-series analysis evaluated the clinical implications of switching high-sensitivity cardiac troponin assays, showing that assay changes affect diagnostic rates and patient management in acute care.

Semaglutide and Hospitalizations in Patients With Obesity and Established Cardiovascular Disease

This SELECT prespecified analysis showed that semaglutide reduces total hospital admissions and length of stay in patients with obesity and established cardiovascular disease, demonstrating healthcare utilization benefits beyond cardiovascular event reduction.

β-Blockers After Myocardial Infarction in Patients With Preserved Ejection Fraction

This meta-analysis of four randomized trials confirmed that beta-blockers after MI in patients with preserved ejection fraction do not improve cardiovascular outcomes. The consolidated evidence definitively supports discontinuation in this population.

Systemic Embolic Events in Atrial Fibrillation

An Individual Patient Data Meta-analysis of 71 683 Participants Randomized to NOAC Versus Warfarin

This individual patient data meta-analysis characterized the incidence, risk factors, and outcomes of systemic embolic events in AF, demonstrating that DOACs effectively prevent both stroke and non-cerebral embolism compared with warfarin.

Multidisciplinary team-guided management of severe aortic stenosis

5-year outcomes following TAVI versus conservative treatment

Multidisciplinary team (MDT) meetings guide treatment decisions in aortic stenosis (AS), especially for borderline or high-risk patients. This retrospective study followed all patients with severe AS discussed at a UK MDT between 2014 and 2016 (178 TAVI, 195 conservative). TAVI patients were younger (81.3 vs 83.5 years) and less frail. Survival at 1, 2 and 5 years was much higher with TAVI (87.6%, 74.7%, 44.9%) than with conservative management (60.8%, 44.2%, 12.1%); median survival was 53 versus 20 months. On multivariable analysis, TAVI was independently associated with lower mortality (HR 0.38). TAVI thus provided a substantial and durable survival advantage over conservative treatment — underscoring the poor prognosis of untreated severe AS and arguing for systematic follow-up of conservatively managed patients too.

Symptom burden and secondary prevention in patients with left ventricular systolic dysfunction after acute myocardial infarction

a nationwide register-based study in Sweden

Contemporary data on patients with left ventricular dysfunction after myocardial infarction (MI) are scarce. In this nationwide Swedish study (49,564 patients from the SWEDEHEART registry, first MI, 2011-2018, no prior heart failure), patients were stratified by degree of LV dysfunction. Compared with normal ejection fraction (≥50%), patients with severely reduced EF (<30%) far more often had dyspnoea (32.3% vs 5.6%; OR 7.45), were more often readmitted (48.1% vs 31.2%) and on sick leave (26.6% vs 9.5%); chest pain and quality of life did not differ. Patients with EF <30% less often took part in education programmes, physiotherapy and regular physical activity. Reduced pump function after infarction is thus associated with a high symptom burden and poorer uptake of secondary prevention — an important focus for aftercare.

Wearable-Derived Training Load and Coronary Atherosclerosis in Middle-Aged and Older Athletes and Physically Active Controls

A New Perspective From the Master@Heart Study

This study used wearable device-derived training load data to investigate the relationship between exercise volume and coronary atherosclerosis in middle-aged and older athletes, addressing the paradox of increased coronary plaque in endurance athletes.

Olezarsen for Managing Severe Hypertriglyceridemia and Pancreatitis Risk.

This trial evaluated olezarsen specifically in patients with severe hypertriglyceridemia and pancreatitis risk, demonstrating dramatic triglyceride reduction and pancreatitis prevention. The APOC3-targeted antisense therapy offers a definitive solution for this dangerous metabolic condition.

KDIGO 2026 clinical practice guideline for Anemia in Chronic Kidney Disease (CKD)

a commentary from the European Renal Best Practice (ERBP).

This ERA commentary on the KDIGO 2026 anemia in CKD guideline discussed the substantial updates including new recommendations for intravenous iron, HIF-prolyl hydroxylase inhibitors, and ESA targets in the contemporary treatment landscape.

Potent P2Y12 Inhibitor Monotherapy vs DAPT After PCI in Patients With and Without STEMI

The NEO-MINDSET Substudy.

The NEO-MINDSET substudy showed that potent P2Y12 inhibitor monotherapy after very early aspirin withdrawal is noninferior to DAPT after PCI in STEMI patients, with fewer bleeding events. The result extends the de-escalation strategy to the acute STEMI population.

Colchicine in acute coronary syndromes

a systematic review and meta-analysis of randomised controlled trials.

This updated meta-analysis of all colchicine trials in acute coronary syndromes confirmed significant MACE reduction with an acceptable safety profile. The anti-inflammatory concept in ACS is now supported by robust pooled evidence.

Drug stewardship for RAS-inhibitors and SGLT2-inhibitors in chronic kidney disease

stay on, restart.

This NDT article emphasized that RAS inhibitors and SGLT2 inhibitors should not be discontinued in CKD patients, showing that drug stewardship programs focusing on continuation and restart of these cornerstone therapies improve outcomes.

Antithrombotic Therapy after Successful Catheter Ablation for Atrial Fibrillation.

This randomized trial investigated the optimal antithrombotic regimen after successful catheter ablation for atrial fibrillation, addressing whether successful ablation eliminates the need for long-term oral anticoagulation.

2026 Heart Disease and Stroke Statistics

A Report of US and Global Data From the American Heart Association

The 2026 AHA Heart Disease and Stroke Statistics report provides comprehensive global data on cardiovascular disease burden, trends, risk factors, and outcomes, serving as the definitive annual reference for cardiovascular epidemiology.

SGLT2 Inhibitors and Kidney Outcomes by Glomerular Filtration Rate and Albuminuria

A Meta-Analysis.

This JAMA meta-analysis confirmed that SGLT2 inhibitors improve kidney outcomes across the entire spectrum of glomerular filtration rate and albuminuria. The universal renoprotective effect supports SGLT2 inhibitor use in virtually all patients with or at risk for chronic kidney disease.

Triple Versus Dual Lipid-Lowering Therapy in Acute Coronary Syndrome

The ES-BempedACS Randomized Clinical Trial.

The ES-BempedACS trial showed that triple lipid-lowering therapy (statin + ezetimibe + bempedoic acid) achieves lower LDL levels faster than dual therapy after ACS. The early intensive approach may reduce residual cardiovascular risk in the vulnerable post-ACS period.

Environmental Stressors and Cardiovascular Health

Acting Locally for Global Impact in a Changing World: A Statement of the European Society of Cardiology, the American College of Cardiology, the American Heart Association, and the World Heart Federation

This AHA statement described how environmental stressors — air pollution, extreme temperatures, noise, and climate change — contribute to cardiovascular disease globally. The document provided a framework for integrating environmental health into cardiovascular prevention strategies.

Socioeconomic and Structural Barriers to Addressing Obesity in Communities

A Scientific Statement From the American Heart Association

This AHA scientific statement addressed the socioeconomic and structural barriers to obesity prevention and treatment in communities, highlighting how poverty, food insecurity, and built environment disproportionately affect cardiovascular health in disadvantaged populations.

Glucagon-like receptor agonists and next-generation incretin-based medications

metabolic, cardiovascular, and renal benefits

This comprehensive Lancet review describes how GLP-1 receptor agonists, originally developed for type 2 diabetes, have expanded into cardiovascular prevention, obesity treatment, heart failure with preserved ejection fraction, and chronic kidney disease. The review covers next-generation agents including dual and triple incretin agonists.

Efficacy and Safety of Oral PCSK9 Inhibitor Enlicitide in Adults With Heterozygous Familial Hypercholesterolemia

A Randomized Clinical Trial.

This phase 3 trial demonstrated that enlicitide, an oral PCSK9 inhibitor, significantly reduced LDL cholesterol in adults with heterozygous familial hypercholesterolemia. An oral daily tablet offers a practical alternative to injectable PCSK9-lowering therapies for patients with genetic hypercholesterolemia.

Efficacy and Safety of Treatment With Low Doses of Spironolactone in Patients With Primary Aldosteronism

A Retrospective Observational Study in a Tertiary Center

This retrospective study evaluated the efficacy and safety of low-dose spironolactone in primary aldosteronism, showing that reduced doses may achieve adequate blood pressure and potassium control with fewer side effects.

CXCR6+ T Cells Drive Immune Checkpoint Inhibitor Myocarditis

This study identified CXCR6+ T cells as key drivers of immune checkpoint inhibitor-associated myocarditis, particularly with combination ICI therapy including anti-LAG-3 agents. The mechanistic insight may guide future prevention and treatment strategies for this serious complication.

DASH-Patterned Groceries and Effects on Blood Pressure

The GoFresh Randomized Clinical Trial.

The GoFresh randomized trial showed that home delivery of DASH-patterned groceries improves dietary quality and lowers blood pressure in Black adults, demonstrating that removing food access barriers translates to measurable health benefit.

Short-Term Anticoagulation Versus Dual Antiplatelet Therapy for Preventing Device Thrombosis Following Left Atrial Appendage Closure

The ANDES Randomized Clinical Trial.

This trial compared short-term anticoagulation with DAPT for preventing device thrombosis after LAA closure, providing the first randomized comparison of antithrombotic strategies in the early post-LAAC period.

Orforglipron, an oral small-molecule GLP-1 receptor agonist, for the treatment of obesity in people with type 2 diabetes (ATTAIN-2)

a phase 3, double-blind, randomised, multicentre, placebo-controlled trial.

The ATTAIN-2 trial demonstrated that orforglipron, an oral GLP-1 receptor agonist, achieved approximately 15% weight loss in adults with obesity and type 2 diabetes. These definitive phase 3 results position daily oral GLP-1 therapy as a practical, needle-free alternative to injectable semaglutide and tirzepatide for obesity treatment in diabetes.

Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes.

This NEJM trial compared tirzepatide with dulaglutide head-to-head on cardiovascular outcomes in type 2 diabetes, providing the first direct comparison of dual versus single incretin agonism for cardiovascular protection.

IMPROVE-DiCE, a 2-Part, Open-Label, Phase 2a Trial Evaluating the Safety and Effectiveness of Ninerafaxstat in Patients With Cardiometabolic Syndromes

The IMPROVE-DiCE phase 2a trial evaluated ninerafaxstat, a novel agent designed to improve diabetic cardiac energetics, in patients with diabetic cardiomyopathy. The study explores a new therapeutic mechanism targeting myocardial metabolism.

2025 ACC/AHA Guideline for the Management of Adults With Congenital Heart Disease

A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines

The 2025 ACC/AHA/HRS/ISACHD/SCAI guideline for adults with congenital heart disease (Circulation edition) provides comprehensive, updated recommendations covering surgical indications, electrophysiology management, pregnancy counseling, and lifelong follow-up for this growing patient population.

Pharmacologic Treatment of Heart Failure With Reduced Ejection Fraction

An Updated Systematic Review and Network Meta-Analysis.

This updated systematic review and network meta-analysis of pharmacological HFrEF treatment confirmed that the four-pillar combination (SGLT2i + ARNI + beta-blocker + MRA) provides the optimal mortality and hospitalization reduction, with quantified contributions from each drug class.

Long-Term Effect of ICDs in Nonischemic Heart Failure With Reduced Ejection Fraction

Extended Follow-Up Analysis of DANISH.

Extended DANISH follow-up confirmed that ICDs in nonischemic HFrEF do not provide significant long-term survival benefit, even with over a decade of follow-up. The persistent negative result reinforces the debate about ICD indications in nonischemic cardiomyopathy.

Complete versus culprit lesion-only revascularisation for acute myocardial infarction (Complete Revascularisation Trialists' Collaboration)

an individual patient data meta-analysis of randomised trials.

This individual patient data meta-analysis from the Complete Revascularisation Trialists provided definitive evidence that complete revascularization reduces cardiovascular death and MI compared with culprit-only PCI in patients with acute MI and multivessel disease. The pooled analysis resolves remaining uncertainty about the strategy.

Major Bleeding With Apixaban vs Aspirin

A Subanalysis of the ARTESiA Randomized Clinical Trial.

This ARTESIA subanalysis detailed the major bleeding events with apixaban versus aspirin in subclinical AF, characterizing the bleeding types and clinical consequences that inform the anticoagulation risk-benefit discussion.

Aggressive Risk Factor Reduction Study for Atrial Fibrillation Implications for Ablation Outcomes

The ARREST-AF Randomized Clinical Trial.

The ARREST-AF study confirmed that aggressive risk factor reduction (weight loss, fitness improvement, sleep apnea treatment) significantly improves catheter ablation outcomes in AF patients, establishing upstream therapy as an essential adjunct to ablation.

Biomarker-Based ABC-AF Risk Scores for Personalized Treatment to Reduce Stroke or Death in Atrial Fibrillation

A Registry-Based, Multicenter, Randomized, Controlled Study.

This study validated biomarker-based ABC-AF risk scores for personalized treatment decisions in AF, showing that prospective application of these scores improves clinical outcomes compared with standard care.

Cardiovascular Effects and Tolerability of GLP-1 Receptor Agonists

A Systematic Review and Meta-Analysis of 99,599 Patients.

This comprehensive meta-analysis of 9 GLP-1 receptor agonist trials summarized all cardiovascular effects and tolerability data, confirming the class-wide benefit on MACE, heart failure, and kidney outcomes with a defined side effect profile.

Dapagliflozin in Patients Hospitalized for Heart Failure

Primary Results of the DAPA ACT HF-TIMI 68 Randomized Clinical Trial and Meta-Analysis of Sodium-Glucose Cotransporter-2 Inhibitors in Patients Hospitalized for Heart Failure.

The DAPA ACT HF-TIMI 68 trial showed that dapagliflozin initiated during heart failure hospitalization was safe and reduced heart failure events. The results support the growing evidence for in-hospital SGLT2 inhibitor initiation during acute heart failure admissions.

2025 ACC Scientific Statement on the Management of Obesity in Adults With Heart Failure

A Report of the American College of Cardiology.

This ACC scientific statement provided a structured framework for obesity management in adults with heart failure, integrating evidence on GLP-1 receptor agonists, tirzepatide, and bariatric surgery as disease-modifying interventions for the obesity-heart failure phenotype.

Beta-Blockers after Myocardial Infarction in Patients without Heart Failure.

This additional definitive trial confirmed that beta-blockers after MI in patients without heart failure do not reduce cardiovascular events or mortality. The overwhelming concordant evidence now firmly supports discontinuing routine post-MI beta-blocker therapy when ejection fraction is preserved.

Beta-Blockers after Myocardial Infarction without Reduced Ejection Fraction.

This definitive meta-analysis confirmed that beta-blockers after myocardial infarction without reduced ejection fraction provide no cardiovascular benefit. Together with ABYSS and REDUCE-AMI, the analysis ends the era of routine long-term beta-blocker therapy after MI when LVEF is preserved.

High-Dose vs. Standard-Dose Influenza Vaccine and Cardiovascular Outcomes in Older Adults

The FLUNITY-HD Prespecified Pooled Analysis

This FLUNITY-HD pooled analysis of over 466,000 older adults demonstrated that high-dose influenza vaccine provides superior cardiovascular protection compared with standard-dose vaccine. The data support preferential use of high-dose formulations in elderly patients with cardiovascular disease.

Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment.

This phase 3 trial demonstrated that orforglipron, an oral small-molecule GLP-1 receptor agonist, produced dose-dependent weight loss of up to 15% in adults with obesity, comparable to subcutaneous semaglutide. An effective oral GLP-1 agonist could transform obesity treatment by removing the barrier of injectable therapy.

2025 AHA/ACC Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults

A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

Simultaneous Circulation edition of the 2025 AHA/ACC hypertension guideline with updated definitions (130/80 mmHg), combination therapy emphasis, and home blood pressure monitoring recommendations.

Safety of Factor XI Inhibition With Abelacimab in Atrial Fibrillation by Kidney Function

A Prespecified Analysis of the AZALEA-TIMI 71 Randomized Clinical Trial.

This AZALEA-TIMI 71 subanalysis confirmed that abelacimab maintains its favorable safety profile across different levels of kidney function in AF, supporting FXI inhibition as a safer anticoagulation option in CKD.

Intensive Blood Pressure Control in Older Patients With Hypertension

6-Year Results of the STEP Trial.

Six-year STEP follow-up confirmed the durable benefit of intensive blood pressure control (SBP <130 mmHg) in older patients with hypertension. The sustained cardiovascular advantage supports long-term commitment to lower blood pressure targets in the elderly.

Effect of Intensive Blood Pressure Control on Stroke

A Prespecified Secondary Analysis of the ESPRIT Trial.

This ESPRIT subanalysis showed that intensive blood pressure control significantly reduces stroke risk, with the greatest benefit in patients with the highest baseline blood pressure. The data support aggressive targets specifically for stroke prevention.

Immediate or Deferred Nonculprit-Lesion PCI in Myocardial Infarction

This NEJM study examined the optimal timing of nonculprit lesion PCI in patients with myocardial infarction and multivessel disease, comparing immediate complete revascularization during the index procedure with a deferred staged approach.

Transcatheter or Surgical Aortic-Valve Replacement in Low-Risk Patients at 7 Years

The 7-year follow-up of TAVR versus surgery in low-risk aortic stenosis patients showed durable outcomes for transcatheter intervention, with mortality and stroke rates remaining comparable to surgical aortic valve replacement. These long-term data support TAVR as a viable option across the full surgical risk spectrum.

Aspirin in Patients with Chronic Coronary Syndrome Receiving Oral Anticoagulation.

This NEJM study examined whether adding aspirin to oral anticoagulation benefits patients with chronic coronary syndrome, finding that OAC monotherapy is sufficient without additional antiplatelet therapy in stable disease.

Heparin administration at first medical contact vs immediately before primary percutaneous coronary intervention

the HELP-PCI trial.

This study evaluated whether early heparin administration at first medical contact improves STEMI outcomes compared with administration immediately before PCI, informing the timing of antithrombotic therapy in acute MI care pathways.

Long-Term Anticoagulation Discontinuation After Catheter Ablation for Atrial Fibrillation

The ALONE-AF Randomized Clinical Trial.

The ALONE-AF trial investigated whether anticoagulation can be safely discontinued after successful catheter ablation for atrial fibrillation. The study addresses one of the most consequential unresolved questions in AF management.

Efficacy and Safety of Baxdrostat in Uncontrolled and Resistant Hypertension.

This study confirmed the efficacy and safety of baxdrostat in patients with both uncontrolled and resistant hypertension. The aldosterone synthase inhibitor demonstrated consistent blood pressure reduction across these challenging treatment populations.

Left atrial appendage occlusion in patients with end-stage renal disease

an individual patient-level meta-analysis.

This individual patient data meta-analysis evaluated LAA occlusion in patients with end-stage renal disease and AF, showing feasibility and potential effectiveness in this high-risk population with limited anticoagulation options.

The relationship between obesity and chronic kidney disease

conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

This KDIGO conference addressed the complex relationship between obesity and CKD, providing consensus conclusions on the direct and indirect mechanisms linking excess adiposity to kidney disease progression and cardiovascular risk.

Impact of Obicetrapib on Major Adverse Cardiovascular Events in High-Risk Patients

A Pooled Analysis.

This pooled analysis suggested that obicetrapib may reduce MACE in high-risk patients, providing the first signal of clinical cardiovascular benefit from a CETP inhibitor after decades of setbacks with earlier agents in this class.

2025 AHA/ACC Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults

A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

The 2025 AHA/ACC hypertension guideline (Hypertension edition) redefines high blood pressure at 130/80 mmHg, endorses combination therapy as first-line treatment, and prioritizes out-of-office blood pressure measurement. The guideline reflects convergence between American and European societies on more aggressive blood pressure targets.

Pulmonary congestion relief by adding dapagliflozin to intravenous loop diuretic in acute heart failure patients.

This study showed that adding dapagliflozin to IV loop diuretics in acute heart failure accelerates pulmonary congestion relief, supporting early SGLT2 inhibitor initiation as an adjunctive decongestion strategy.

Digitoxin in Patients with Heart Failure and Reduced Ejection Fraction.

This NEJM trial showed that digitoxin reduced heart failure hospitalization in patients with HFrEF receiving contemporary guideline-directed medical therapy. The result repositions cardiac glycosides as a useful adjunct in the modern era of quadruple therapy for heart failure.

Effect of evolocumab on saphenous vein graft patency after coronary artery bypass surgery (NEWTON-CABG CardioLink-5)

an international, randomised, double-blind, placebo-controlled trial.

The NEWTON-CABG trial showed that evolocumab improved saphenous vein graft patency after CABG through intensive LDL cholesterol lowering. The finding establishes aggressive lipid therapy as a graft-protective strategy after coronary bypass surgery.

Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist, in Early Type 2 Diabetes.

This phase 3 NEJM trial demonstrated that orforglipron, an oral GLP-1 receptor agonist, significantly improved HbA1c and body weight in patients with early type 2 diabetes. The results confirm the efficacy of oral nonpeptide GLP-1 agonism as a practical therapy for early-stage metabolic disease.

2025 AHA/ACC Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults

A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

The 2025 AHA/ACC hypertension guideline lowered the definition of hypertension to 130/80 mmHg, converging with the 2024 ESC guidelines. The document emphasizes home blood pressure monitoring, initial combination therapy, and integrates GLP-1 receptor agonists as blood pressure-lowering agents in patients with obesity and hypertension.

β blockers after myocardial infarction with mildly reduced ejection fraction

an individual patient data meta-analysis of randomised controlled trials.

This individual patient data meta-analysis examined beta-blockers after MI with mildly reduced ejection fraction (40-49%), a gray zone between preserved and reduced EF. The data suggest a modest benefit in this subgroup, informing the nuanced decision about beta-blocker continuation.

Multidomain Rehabilitation for Older Patients with Myocardial Infarction.

This NEJM trial evaluated multidomain rehabilitation (physical, cognitive, nutritional, psychosocial) in older patients after MI. The comprehensive approach improved functional outcomes, supporting holistic rehabilitation for elderly cardiac patients.

Influence of Type 2 Diabetes on the Effects of Tirzepatide in Patients With Heart Failure and a Preserved Ejection Fraction With Obesity

A Prespecified Stratification-Based Analysis.

This SUMMIT analysis confirmed that tirzepatide's benefit in HFpEF is consistent regardless of type 2 diabetes status, showing that the dual incretin agonist works through obesity-related mechanisms independent of glycemic effects.

Optimal medical care and coronary flow capacity-guided myocardial revascularization vs usual care for chronic coronary artery disease

the CENTURY trial.

The CENTURY randomized trial tested a comprehensive strategy integrating coronary flow capacity-guided revascularization with intensive lifestyle modification against usual care for chronic coronary disease, exploring a physiologically optimized management approach.

Cost-effectiveness of apixaban vs. aspirin for the reduction of thrombo-embolism in high-risk patients with device-detected atrial fibrillation

insights from the ARTESiA trial.

This cost-effectiveness analysis showed that apixaban is cost-effective compared with aspirin for thromboembolic prevention in high-risk patients with subclinical AF, supporting anticoagulation in device-detected arrhythmia.

Diabetes and Obesity and Treatment Effect of Early Rhythm Control vs Usual Care in Patients With Atrial Fibrillation

A Secondary Analysis of the EAST-AFNET 4 Randomized Clinical Trial.

This EAST-AFNET 4 subanalysis confirmed that the benefit of early rhythm control in AF is consistent in patients with and without diabetes and obesity, supporting universal early rhythm management.

Conduction system pacing vs. biventricular pacing for cardiac resynchronization

the CSP-SYNC randomized single centre study.

The CSP-SYNC trial comparing conduction system pacing (His bundle or left bundle branch area) with biventricular pacing for CRT showed that conduction system pacing is noninferior and potentially superior. The results support physiologic pacing as a viable CRT alternative.

Blood pressure-lowering efficacy of antihypertensive drugs and their combinations

a systematic review and meta-analysis of randomised, double-blind, placebo-controlled trials.

This comprehensive meta-analysis quantified the blood pressure-lowering efficacy of all antihypertensive drug classes and their combinations, providing an evidence-based reference for estimating expected blood pressure reduction with different regimens.

Preventive percutaneous coronary intervention for non-flow-limiting vulnerable atherosclerotic coronary plaques in diabetes

the PREVENT trial.

Long-term PREVENT data confirmed the benefit of preventive PCI for vulnerable plaques identified by IVUS/OCT in diabetic patients. The paradigm of treating non-flow-limiting high-risk lesions continues to gain evidence.

Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity.

This pivotal trial of CagriSema (cagrilintide plus semaglutide) in adults with overweight or obesity demonstrated up to 25% body weight reduction, substantially exceeding semaglutide monotherapy. The amylin–GLP-1 combination represents the most effective pharmacological weight loss therapy to date and may redefine obesity treatment targets.

Outcomes in Older Patients After Switching to a Newer Anticoagulant or Remaining on Warfarin

The COMBINE-AF Substudy.

This COMBINE-AF analysis showed that switching from warfarin to a NOAC in older AF patients is associated with improved outcomes compared with remaining on warfarin, supporting anticoagulant modernization even in the elderly.

Sodium-Glucose Cotransporter 2 Inhibitor With and Without an Aldosterone Antagonist for Heart Failure With Preserved Ejection Fraction

The SOGALDI-PEF Trial.

This analysis showed that combining SGLT2 inhibitors with aldosterone antagonists in HFpEF provides additive cardiovascular benefit beyond either drug class alone, supporting the emerging four-pillar approach for preserved ejection fraction heart failure.

Abelacimab Versus Rivaroxaban in Patients With Atrial Fibrillation on Antiplatelet Therapy

A Prespecified Analysis of the AZALEA-TIMI 71 Trial.

This AZALEA-TIMI 71 subanalysis confirmed that abelacimab causes less bleeding than rivaroxaban even in AF patients on concurrent antiplatelet therapy, the highest-bleeding-risk scenario for anticoagulation.

Lorundrostat in Participants With Uncontrolled Hypertension and Treatment-Resistant Hypertension

The Launch-HTN Randomized Clinical Trial.

Phase 3 results of lorundrostat confirmed significant blood pressure reduction in both uncontrolled and treatment-resistant hypertension. The aldosterone synthase inhibitor class is now supported by multiple positive phase 3 trials.

Impact of Body Mass Index, Central Adiposity, and Weight Loss on the Benefits of Tirzepatide in HFpEF

The SUMMIT Trial.

This SUMMIT analysis confirmed that tirzepatide benefits HFpEF patients consistently regardless of BMI, central adiposity measures, or degree of weight loss achieved, supporting the drug across the obesity spectrum.

Long-term benefits of atorvastatin on the incidence of cardiovascular events

the ASCOT-Legacy 20-year follow-up.

The ASCOT-Legacy 20-year follow-up showed that cardiovascular benefits of atorvastatin remain measurable two decades after the original trial, demonstrating one of the longest legacy effects of statin therapy ever documented.

COOPERATIVE-PFA

A Three-Arm Randomized Controlled Trial.

The COOPERATIVE-PFA three-arm randomized trial directly compared pulsed field ablation, radiofrequency ablation, and cryoablation for atrial fibrillation, providing the first head-to-head-to-head comparison of all three energy sources for pulmonary vein isolation.

10-Year Outcome of Complete or Infarct Artery-Only Revascularization in STEMI With Multivessel Disease

The DANAMI-3-PRIMULTI Study.

Ten-year DANAMI-3-PRIMULTI results confirmed the durable benefit of complete revascularization over culprit-only PCI in patients with STEMI and multivessel disease. The survival advantage persisted over a decade of follow-up.

Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously

results from a phase 1b/2a randomised controlled study.

Phase 2 results of subcutaneous amycretin confirmed dose-dependent weight loss and metabolic improvement. The dual GLP-1/amylin receptor agonist mechanism offers a novel approach to obesity treatment with potent appetite suppression.

Safety, tolerability, pharmacokinetics, and pharmacodynamics of the first-in-class GLP-1 and amylin receptor agonist, amycretin

a first-in-human, phase 1, double-blind, randomised, placebo-controlled trial.

This first-in-human phase 1 trial of amycretin, a unimolecular dual GLP-1 and amylin receptor agonist, demonstrated up to 10% weight loss in 12 weeks with potent appetite suppression. The single-molecule dual agonist approach offers manufacturing and dosing advantages over combination products like CagriSema.

Catheter Ablation vs Lifestyle Modification With Antiarrhythmic Drugs to Treat Atrial Fibrillation

PRAGUE-25 Trial.

The PRAGUE-25 trial compared catheter ablation with lifestyle modification plus antiarrhythmic drugs in AF patients with obesity. The results inform the choice between invasive and comprehensive conservative management strategies for atrial fibrillation.

Colchicine for secondary prevention of vascular events

a meta-analysis of trials.

This meta-analysis of all colchicine trials in secondary cardiovascular prevention confirmed a 20-30% reduction in MACE with an acceptable safety profile. The pooled evidence from COLCOT, LoDoCo2, and CLEAR SYNERGY consolidates colchicine as a cost-effective anti-inflammatory strategy for atherosclerotic disease.

Long-term trials of colchicine for secondary prevention of vascular events

a meta-analysis.

This meta-analysis of long-term colchicine trials confirmed that colchicine significantly reduces recurrent vascular events in secondary prevention. After COLCOT, LoDoCo2, and CLEAR SYNERGY, the pooled long-term data consolidate colchicine as a cost-effective anti-inflammatory strategy.

Collaboration on the optimal timing of anticoagulation after ischaemic stroke and atrial fibrillation

a systematic review and prospective individual participant data meta-analysis of randomised controlled trials (CATALYST).

This collaborative systematic review combined data on the optimal timing of anticoagulation initiation after ischemic stroke in AF patients, providing the most comprehensive evidence for early versus delayed DOAC start.

Safety and Efficacy of Obicetrapib in Patients at High Cardiovascular Risk.

Phase 3 data confirmed that obicetrapib, a highly selective CETP inhibitor, significantly lowers LDL cholesterol with an acceptable safety profile in patients at high cardiovascular risk. The results position obicetrapib as the first CETP inhibitor with genuine clinical promise.

Near-universal prevalence of central adiposity in heart failure with preserved ejection fraction

the PARAGON-HF trial.

This PARAGON-HF analysis showed that central adiposity is nearly universal in HFpEF regardless of BMI category, reinforcing the concept that visceral fat — not just body weight — is central to the obesity-HFpEF phenotype.

Add-On Treatment With Zilebesiran for Inadequately Controlled Hypertension

The KARDIA-2 Randomized Clinical Trial.

The KARDIA-2 trial showed that zilebesiran, an siRNA targeting hepatic angiotensinogen, significantly reduced blood pressure when added to existing antihypertensive therapy in patients with inadequately controlled hypertension. The twice-yearly injectable represents a novel approach to treatment-resistant blood pressure.

Long-Acting Factor XI Inhibition and Periprocedural Bleeding

An Analysis From AZALEA-TIMI 71.

This AZALEA-TIMI 71 analysis showed that abelacimab (long-acting factor XI inhibitor) reduces periprocedural bleeding compared with rivaroxaban, demonstrating the safety advantage of factor XI inhibition around invasive procedures.

Spironolactone vs Amiloride for Resistant Hypertension

A Randomized Clinical Trial.

This randomized trial demonstrated that spironolactone was superior to amiloride for blood pressure reduction in patients with resistant hypertension. The result confirmed spironolactone as the preferred fourth-line agent and defined the comparative effectiveness of potassium-sparing diuretics.

Antihypertensive Medication Timing and Cardiovascular Events and Death

The BedMed Randomized Clinical Trial.

The BedMed trial definitively confirmed that the timing of antihypertensive medication (morning versus evening) has no effect on cardiovascular outcomes or death. Together with the TIME trial, this eliminates chronotherapy as a meaningful consideration in hypertension management.

The Impact of frailty on the effectiveness of intensive blood pressure control for patients with type 2 diabetes

a secondary analysis of a randomised controlled trial.

This analysis showed that moderately frail patients with type 2 diabetes still benefit from intensive blood pressure control, while the benefit may be attenuated in the most severely frail, guiding treatment intensity by frailty status.

Oral Semaglutide and Cardiovascular Outcomes in People With Type 2 Diabetes, According to SGLT2i Use

Prespecified Analyses of the SOUL Randomized Trial.

This SOUL subanalysis confirmed that oral semaglutide's cardiovascular benefit is consistent regardless of background SGLT2 inhibitor use, supporting the combination of both drug classes for comprehensive cardiometabolic protection.

Intravenous Ferric Carboxymaltose in Heart Failure With Iron Deficiency

The FAIR-HF2 DZHK05 Randomized Clinical Trial.

The FAIR-HF2 trial confirmed that intravenous ferric carboxymaltose in patients with chronic heart failure and iron deficiency significantly reduced the composite of cardiovascular death and heart failure hospitalization. This provides the definitive evidence that had been missing from earlier, smaller trials of intravenous iron in heart failure.

2025 ACC/AHA Guideline for the Management of Patients With Acute Coronary Syndromes

A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

The 2025 ACC/AHA ACS guideline (JACC edition) provides updated recommendations for acute coronary syndromes incorporating evidence from ABYSS, REDUCE-AMI, COMPLETE, and other contemporary trials, endorsing DAPT de-escalation, optional beta-blockers after MI with preserved EF, and troponin-guided management pathways.

An Oral PCSK9 Inhibitor for Treatment of Hypercholesterolemia

The PURSUIT Randomized Trial.

The PURSUIT trial of an oral PCSK9 inhibitor demonstrated significant LDL cholesterol reduction in patients with hypercholesterolemia. An effective oral PCSK9 inhibitor could dramatically expand access to advanced lipid-lowering therapy beyond injectable monoclonal antibodies and siRNA agents.

Randomized trial to assess worsening renal function by adding dapagliflozin for acute decompensated heart failure.

This randomized trial confirmed that dapagliflozin does not worsen renal function when added for acute decompensated heart failure, providing safety data for early SGLT2 inhibitor initiation during AHF hospitalization.

Novel Controlled Metabolic Accelerator for Obesity-Related HFpEF

The HuMAIN-HFpEF Randomized Clinical Trial.

The HuMAIN-HFpEF trial tested a novel controlled metabolic accelerator for obesity-related HFpEF, exploring a new pharmacological mechanism for targeting excess body fat in this challenging heart failure phenotype.

FFR-Guided Percutaneous Coronary Intervention vs Coronary Artery Bypass Grafting in Patients With Diabetes.

This analysis compared FFR-guided PCI with CABG in patients with diabetes, evaluating whether contemporary physiologically optimized percutaneous intervention can narrow the outcome gap with surgery in the diabetic population.

Oral Semaglutide and Cardiovascular Outcomes in High-Risk Type 2 Diabetes.

The SOUL trial demonstrated that oral semaglutide significantly reduced major adverse cardiovascular events in patients with type 2 diabetes and high cardiovascular risk. This is the first cardiovascular outcomes trial to show benefit for an oral GLP-1 receptor agonist, removing the barrier of injectable administration for cardiovascular prevention in diabetes.

Fixed-dose combination of obicetrapib and ezetimibe for LDL cholesterol reduction (TANDEM)

a phase 3, randomised, double-blind, placebo-controlled trial.

The TANDEM trial demonstrated that a fixed-dose combination of obicetrapib (a CETP inhibitor) and ezetimibe reduced LDL cholesterol by 55-60% in statin-treated patients. This is the first positive result for a modern CETP inhibitor in combination therapy, reviving the mechanism after decades of setbacks.

Effect of Empagliflozin on the Mechanisms Driving Erythropoiesis and Iron Mobilization in Patients With Heart Failure

The EMPEROR Program.

This mechanistic study showed that empagliflozin stimulates erythropoiesis and iron mobilization in heart failure through hypoxia-inducible factor pathway activation, explaining the hemoglobin increases observed during SGLT2 inhibitor therapy.

Interplay of Chronic Kidney Disease and the Effects of Tirzepatide in Patients With Heart Failure, Preserved Ejection Fraction, and Obesity

The SUMMIT Trial.

This analysis showed that CKD does not attenuate the benefit of tirzepatide in HFpEF with obesity, supporting the dual incretin agonist across the cardiorenal comorbidity spectrum.

Lorundrostat Efficacy and Safety in Patients with Uncontrolled Hypertension.

This phase 3 trial demonstrated that lorundrostat, a selective aldosterone synthase inhibitor, significantly reduced blood pressure in patients with uncontrolled hypertension on existing therapy. The results add to the growing evidence for aldosterone synthase inhibition as a new treatment class for resistant and difficult-to-treat hypertension.

Semaglutide and walking capacity in people with symptomatic peripheral artery disease and type 2 diabetes (STRIDE)

a phase 3b, double-blind, randomised, placebo-controlled trial.

The STRIDE trial investigated whether semaglutide improves walking capacity in patients with symptomatic peripheral artery disease and type 2 diabetes, testing GLP-1 receptor agonism for PAD-specific functional outcomes.

Pulsed Field or Cryoballoon Ablation for Paroxysmal Atrial Fibrillation.

This randomized trial showed that pulsed field ablation was noninferior to cryoballoon ablation for pulmonary vein isolation in paroxysmal atrial fibrillation, with comparable efficacy and safety. The result positions PFA as an alternative to established thermal energy sources for AF ablation.

Dapagliflozin in Patients Undergoing Transcatheter Aortic-Valve Implantation.

This NEJM trial evaluated dapagliflozin in patients undergoing TAVI, exploring whether SGLT2 inhibition provides additional cardiac protection in this high-risk valvular heart disease population.

Empagliflozin in resistant hypertension and heart failure with preserved ejection fraction

the EMPEROR-Preserved trial.

This EMPEROR-Preserved subanalysis showed that empagliflozin improves blood pressure in patients with resistant hypertension and HFpEF, providing additional hemodynamic benefit in this difficult-to-treat overlap population.

Sodium-glucose co-transporter 2 inhibitors and new-onset diabetes in cardiovascular or kidney disease.

This analysis showed that SGLT2 inhibitors reduce the risk of new-onset diabetes in patients with cardiovascular or kidney disease, adding a metabolic prevention benefit to their established cardiorenal protection.

Left Atrial Appendage Closure after Ablation for Atrial Fibrillation.

This NEJM trial investigated whether left atrial appendage closure combined with catheter ablation for atrial fibrillation can reduce stroke risk and enable anticoagulation cessation. The results inform the decision about combining structural and rhythm interventions for long-term AF management.

2025 ACC/AHA Guideline for the Management of Patients With Acute Coronary Syndromes

A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

The 2025 ACC/AHA ACS guideline integrates contemporary evidence on DAPT de-escalation, routine complete revascularization, troponin-based diagnosis, and post-MI therapy. Notably, long-term beta-blockers are no longer mandated after MI with preserved ejection fraction, reflecting ABYSS and REDUCE-AMI results.

Efficacy and Safety of Aldosterone Synthase Inhibitors for Hypertension

A Meta-Analysis of Randomized Controlled Trials and Systematic Review.

This meta-analysis of all randomized trials with aldosterone synthase inhibitors (baxdrostat, lorundrostat) confirmed significant blood pressure reduction in patients with hypertension. The pooled evidence established aldosterone synthase inhibition as a new drug class with a favorable efficacy and safety profile.

Meta-analysis of sotagliflozin, a dual sodium-glucose-cotransporter 1/2 inhibitor, for heart failure in type 2 diabetes.

This meta-analysis confirmed that sotagliflozin, a dual SGLT1/2 inhibitor, reduces cardiovascular events and hospitalizations in heart failure patients with type 2 diabetes, supporting the dual transporter inhibition approach.

Flecainide acetate inhalation solution for cardioversion of recent-onset, symptomatic atrial fibrillation

results of the phase 3 RESTORE-1 trial.

The RESTORE-1 trial demonstrated that inhaled flecainide rapidly and effectively cardioverted recent-onset symptomatic atrial fibrillation in an outpatient setting. The needle-free, self-administered formulation offers a patient-controlled 'pill-in-the-pocket' alternative with faster onset than oral antiarrhythmic drugs.

Intensive Blood-Pressure Control in Patients with Type 2 Diabetes.

This large randomized trial showed that intensive blood pressure control (systolic <120 mmHg) significantly reduced cardiovascular events compared with standard treatment (<140 mmHg) in patients with type 2 diabetes and elevated cardiovascular risk. The results align with SPRINT and extend the evidence for aggressive blood pressure targets specifically to the diabetic population.

Antithrombotic Therapy to Minimize Total Events After ACS or PCI in Atrial Fibrillation

Insights From AUGUSTUS.

This comprehensive AUGUSTUS analysis identified the antithrombotic regimen that minimizes the total burden of both bleeding and ischemic events in AF patients after ACS or PCI, definitively supporting apixaban plus P2Y12 inhibitor without aspirin.

Anticoagulation and Antiplatelet Therapy for Atrial Fibrillation and Stable Coronary Disease

Meta-Analysis of Randomized Trials.

This meta-analysis confirmed that oral anticoagulant monotherapy without antiplatelet therapy is the preferred long-term strategy for AF patients with stable coronary disease, with no ischemic cost from dropping the antiplatelet agent.

Age and Sex Differences in Efficacy of Treatments for Type 2 Diabetes

A Network Meta-Analysis.

This network meta-analysis showed that the efficacy of SGLT2 inhibitors and GLP-1 agonists for type 2 diabetes treatment is consistent across age and sex subgroups, supporting equitable prescribing.

Transcatheter Aortic Valve Replacement in Patients With Systolic Heart Failure and Moderate Aortic Stenosis

TAVR UNLOAD.

The TAVR UNLOAD trial explored TAVR in patients with HFrEF and moderate (not severe) aortic stenosis. The results inform the growing debate about the role of valve intervention in patients where hemodynamic afterload reduction may benefit ventricular recovery even below conventional severity thresholds for aortic stenosis.

Catheter Ablation or Antiarrhythmic Drugs for Ventricular Tachycardia.

The VANISH2 trial confirmed that catheter ablation was superior to escalation of antiarrhythmic drug therapy for recurrent ventricular tachycardia in patients with ischemic cardiomyopathy, significantly reducing VT recurrence and ICD shocks. The results strengthen the position of early ablation in VT management.

Colchicine in Acute Myocardial Infarction.

The CLEAR SYNERGY trial demonstrated that colchicine initiated within days of acute MI reduced major cardiovascular events by 33% compared with placebo over a median of 3 years. This is the third major positive trial of colchicine in atherosclerotic disease, after COLCOT and LoDoCo2, consolidating anti-inflammatory therapy as a pillar of secondary prevention.

Routine Spironolactone in Acute Myocardial Infarction.

This NEJM trial showed that routine spironolactone after acute MI in patients without heart failure or reduced ejection fraction did not significantly reduce the primary composite endpoint. The result limits MRA use after MI to those with established HF or reduced LVEF.

Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity.

The SUMMIT trial showed that tirzepatide, a dual GIP/GLP-1 receptor agonist, significantly reduced heart failure hospitalization and cardiovascular death in patients with HFpEF and obesity, with substantial improvements in symptoms, quality of life, and body weight. This establishes tirzepatide alongside semaglutide as a transformative therapy for obesity-related heart failure.

Continuation versus Interruption of Oral Anticoagulation during TAVI.

This NEJM trial showed that continuation of oral anticoagulation during TAVI was noninferior to interruption for the composite of bleeding and thromboembolic events. The result simplifies periprocedural management by avoiding the complexity of anticoagulation bridging.

Coronary CT angiography-guided management of patients with stable chest pain

10-year outcomes from the SCOT-HEART randomised controlled trial in Scotland.

The 10-year SCOT-HEART follow-up confirmed that coronary CT angiography-guided management of stable chest pain provides sustained cardiovascular benefit, with persistent reductions in MI. The long-term data support CCTA as a cost-effective first-line investigation.

Abelacimab versus Rivaroxaban in Patients with Atrial Fibrillation.

This trial demonstrated that abelacimab, a factor XI-targeting monoclonal antibody, significantly reduced major bleeding compared with rivaroxaban while maintaining comparable efficacy in stroke prevention in patients with atrial fibrillation. After the failure of the small-molecule FXIa inhibitor asundexian, abelacimab revives the prospect of safer anticoagulation through factor XI inhibition.

Oral Muvalaplin for Lowering of Lipoprotein(a)

A Randomized Clinical Trial.

This randomized trial demonstrated that muvalaplin, the first oral lipoprotein(a) inhibitor, produced dose-dependent Lp(a) reductions of up to 85% with an acceptable safety profile. An oral Lp(a)-lowering agent could dramatically expand access to treatment compared with injectable alternatives like olpasiran and pelacarsen.

Early Intervention in Patients With Asymptomatic Severe Aortic Stenosis and Myocardial Fibrosis

The EVOLVED Randomized Clinical Trial.

The EVOLVED trial demonstrated that early aortic valve intervention guided by myocardial fibrosis on cardiac MRI reduced all-cause death and unplanned heart failure hospitalization in patients with asymptomatic severe aortic stenosis. The results support an imaging-guided, proactive approach to valve replacement timing.

Transcatheter Edge-to-Edge Repair for Severe Isolated Tricuspid Regurgitation

The Tri.Fr Randomized Clinical Trial.

The Tri.Fr trial showed that transcatheter edge-to-edge repair for severe isolated tricuspid regurgitation significantly improved functional capacity and quality of life compared with optimal medical therapy alone. The results advance the interventional management of tricuspid valve disease.

Transcatheter Valve Replacement in Severe Tricuspid Regurgitation.

This NEJM trial showed that transcatheter tricuspid valve replacement significantly improved symptoms, quality of life, and functional status in patients with severe tricuspid regurgitation. The results establish transcatheter replacement as a viable option for severe TR when repair alone may be insufficient.

Plozasiran for Managing Persistent Chylomicronemia and Pancreatitis Risk.

This NEJM trial demonstrated that plozasiran, an siRNA targeting APOC3, dramatically reduced triglycerides and prevented pancreatitis episodes in patients with persistent chylomicronemia from both genetic and multifactorial causes. The twice-yearly injectable provides a definitive solution for this life-threatening lipid disorder.

Efficacy and Safety of Finerenone Across the Ejection Fraction Spectrum in Heart Failure With Mildly Reduced or Preserved Ejection Fraction

A Prespecified Analysis of the FINEARTS-HF Trial.

This FINEARTS-HF subanalysis confirmed that finerenone's benefit on heart failure events is consistent across the entire ejection fraction spectrum from 40% to 100%. The uniform effect establishes finerenone as a broadly applicable therapy for heart failure with mildly reduced or preserved ejection fraction.

Asundexian versus Apixaban in Patients with Atrial Fibrillation.

The OCEANIC-AF trial showed that asundexian, a factor XIa inhibitor, was inferior to apixaban in preventing stroke and systemic embolism in patients with atrial fibrillation, without a meaningful reduction in bleeding. This definitive negative result dampened expectations for factor XIa inhibition as a replacement for standard anticoagulation in AF.

PCI in Patients Undergoing Transcatheter Aortic-Valve Implantation.

This NEJM trial showed that PCI of coronary stenoses before TAVR did not improve the composite of death or cardiovascular hospitalization compared with conservative management. The result argued against routine pre-TAVR coronary revascularization in patients with stable coronary disease.

Cardiovascular, Kidney, and Safety Outcomes With GLP-1 Receptor Agonists Alone and in Combination With SGLT2 Inhibitors in Type 2 Diabetes

A Systematic Review and Meta-Analysis.

This comprehensive meta-analysis confirmed that GLP-1 receptor agonists and SGLT2 inhibitors provide complementary cardiovascular and kidney protection in patients with type 2 diabetes. The combination yields additive benefits on MACE, heart failure, and renal outcomes, supporting dual cardiometabolic therapy.

Effect of Screening for Undiagnosed Atrial Fibrillation on Stroke Prevention.

This randomized trial of AF screening versus usual care demonstrated that screening detects more undiagnosed AF and increases anticoagulation initiation, though the impact on stroke incidence was not statistically significant. Larger, longer-term studies are needed to demonstrate the clinical benefit of population-level AF screening.

Transcatheter Repair versus Mitral-Valve Surgery for Secondary Mitral Regurgitation.

The MATTERHORN trial demonstrated that transcatheter edge-to-edge mitral valve repair was noninferior to surgical mitral valve intervention for reducing mitral regurgitation severity in patients with heart failure and secondary MR, with fewer perioperative complications. The results support the transcatheter approach as a less invasive alternative.

Transcatheter Valve Repair in Heart Failure with Moderate to Severe Mitral Regurgitation.

The RESHAPE-HF2 trial showed that transcatheter mitral valve repair improved outcomes in patients with heart failure and moderate-to-severe secondary mitral regurgitation, adding to the COAPT evidence for device therapy in functional MR. The positive result helps define the patient population that benefits from intervention.

Quantitative flow ratio versus fractional flow reserve for coronary revascularisation guidance (FAVOR III Europe)

a multicentre, randomised, non-inferiority trial.

The FAVOR III Europe trial demonstrated that quantitative flow ratio (QFR) was noninferior to fractional flow reserve (FFR) for guiding coronary revascularization decisions. The wire-free, computational approach offers a practical and time-saving alternative to pressure-based physiological assessment.

Invasive Treatment Strategy for Older Patients with Myocardial Infarction.

This NEJM trial demonstrated that an invasive treatment strategy in patients aged 80 years or older with non-STEMI significantly reduced the composite of MI, urgent revascularization, stroke, and death compared with conservative management. The results support active intervention even in the oldest-old MI population.

Complete Versus Culprit-Only Revascularization in Older Patients With ST-Segment-Elevation Myocardial Infarction

An Individual Patient Meta-Analysis.

This individual patient data analysis confirmed that complete revascularization is superior to culprit-only PCI in older patients with STEMI and multivessel disease, consistent with the primary FIRE trial results. The pooled evidence supports complete revascularization regardless of age.

Adjudication of Hospitalizations and Deaths in the IRONMAN Trial of Intravenous Iron for Heart Failure.

This adjudicated reanalysis of the IRONMAN trial confirmed that intravenous ferric derisomaltose reduces heart failure hospitalization in patients with heart failure and iron deficiency, strengthening the evidence when accounting for misclassified events in the original analysis.

Finerenone in Heart Failure with Mildly Reduced or Preserved Ejection Fraction.

The FINEARTS-HF trial demonstrated that finerenone significantly reduced heart failure events in patients with HFmrEF and HFpEF, extending the benefit of mineralocorticoid receptor antagonism beyond HFrEF. This landmark result establishes finerenone as the first nonsteroidal MRA with proven efficacy across the broader heart failure spectrum.

Effects of Semaglutide on Heart Failure Outcomes in Diabetes and Chronic Kidney Disease in the FLOW Trial.

This FLOW subanalysis demonstrated that semaglutide significantly reduces heart failure events in patients with type 2 diabetes and chronic kidney disease. The cardiorenal protective effect positions GLP-1 receptor agonists alongside SGLT2 inhibitors as foundational therapy for the diabetic cardiorenal population.

Beta-Blocker Interruption or Continuation after Myocardial Infarction.

The REDUCE-AMI trial showed that continuation versus interruption of long-term beta-blocker therapy after myocardial infarction in patients with preserved ejection fraction made no difference in the composite of death or MI. Together with ABYSS, this provides definitive evidence that beta-blockers can be safely discontinued after MI when LVEF is preserved.

Semaglutide and blood pressure

an individual patient data meta-analysis.

This individual patient data meta-analysis showed that semaglutide produces dose-dependent and clinically significant blood pressure reduction independent of weight loss. The antihypertensive effect adds another mechanism through which GLP-1 receptor agonists provide cardiovascular protection.

2024 ESC Guidelines for the management of elevated blood pressure and hypertension.

The 2024 ESC hypertension guidelines lowered the treatment threshold to 130/80 mmHg and set a target of 120–129/70–79 mmHg for most patients, converging with the evidence from SPRINT and STEP. The guideline endorses initial combination therapy and emphasizes home blood pressure monitoring as central to management.

2024 ESC Guidelines for the management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS).

The 2024 ESC atrial fibrillation guidelines introduced the AF-CARE pathway (Comorbidities and risk factors, Anticoagulation, Rate and Rhythm control, Evaluation and reassessment) as a structured management approach. The guideline recognized pulsed field ablation as a new technique and emphasized weight management and early rhythm control.

2024 ACC Expert Consensus Decision Pathway on Clinical Assessment, Management, and Trajectory of Patients Hospitalized With Heart Failure Focused Update

A Report of the American College of Cardiology Solution Set Oversight Committee.

The 2024 ACC Expert Consensus provided a structured decision pathway for clinical assessment, management, and trajectory of HFpEF patients during hospitalization, including fluid management, SGLT2 inhibitor initiation, and transition to outpatient care.

Mineralocorticoid receptor antagonists in heart failure

an individual patient level meta-analysis.

This individual patient data meta-analysis confirmed that mineralocorticoid receptor antagonists significantly improve survival in patients with HFrEF, with consistent benefit across subgroups. The analysis found insufficient evidence for benefit in HFpEF, underscoring the distinct role of nonsteroidal MRAs like finerenone in that population.

Temporary mechanical circulatory support in infarct-related cardiogenic shock

an individual patient data meta-analysis of randomised trials with 6-month follow-up.

This individual patient data meta-analysis of mechanical circulatory support in cardiogenic shock showed that Impella CP (from DanGer Shock) provides survival benefit, while ECMO (from ECLS-SHOCK) does not. The analysis established Impella as the preferred percutaneous support device for infarct-related cardiogenic shock.

Zodasiran, an RNAi Therapeutic Targeting ANGPTL3, for Mixed Hyperlipidemia.

This NEJM trial of zodasiran, an siRNA targeting ANGPTL3, demonstrated significant reductions in triglycerides, LDL cholesterol, and non-HDL cholesterol in patients with mixed hyperlipidemia. The results establish a new RNA-based mechanism for comprehensive lipid lowering beyond PCSK9 and APOC3 targets.

Plozasiran, an RNA Interference Agent Targeting APOC3, for Mixed Hyperlipidemia.

This NEJM trial of plozasiran, an RNA interference agent targeting APOC3, demonstrated dramatic triglyceride and VLDL reduction in patients with mixed hyperlipidemia. The twice-yearly injectable offers a durable approach to treating triglyceride-rich lipoprotein excess, a key driver of residual cardiovascular risk.

Semaglutide versus placebo in patients with heart failure and mildly reduced or preserved ejection fraction

a pooled analysis of the SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM randomised trials.

This pooled analysis of semaglutide trials in HFpEF with ejection fraction ≥40% and obesity confirmed significant improvements in symptoms, exercise function, body weight, and inflammation markers. The consistent benefit across the mildly reduced and preserved ejection fraction spectrum supports semaglutide as a core therapy for the obesity-HFpEF phenotype.

Ticagrelor monotherapy for acute coronary syndrome

an individual patient data meta-analysis of TICO and T-PASS trials.

This individual patient data meta-analysis of four trials confirmed that ticagrelor monotherapy after short-duration DAPT in ACS patients reduces bleeding without increasing ischemic events. The pooled patient-level data provide the highest level of evidence for this de-escalation strategy.

Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure

a prespecified analysis of the SELECT trial.

This SELECT subanalysis showed that semaglutide reduces cardiovascular events in obese patients with prevalent heart failure, with consistent benefit across heart failure subtypes. The finding supports GLP-1 receptor agonists for cardiovascular prevention in the obesity-heart failure overlap population.

Lowering systolic blood pressure to less than 120 mm Hg versus less than 140 mm Hg in patients with high cardiovascular risk with and without diabetes or previous stroke

an open-label, blinded-outcome, randomised trial.

This meta-analysis confirmed that targeting a systolic blood pressure below 120 mmHg versus below 140 mmHg significantly reduces cardiovascular events and mortality in patients with high cardiovascular risk, including those with diabetes. The data reinforce aggressive blood pressure targets.

Long-term colchicine for the prevention of vascular recurrent events in non-cardioembolic stroke (CONVINCE)

a randomised controlled trial.

The CONVINCE trial showed that long-term colchicine did not significantly reduce recurrent vascular events after non-cardioembolic stroke. The negative result suggested that the anti-inflammatory benefit of colchicine in coronary disease may not extend to all atherothrombotic vascular beds.

Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes.

The FLOW trial demonstrated that semaglutide significantly slowed kidney disease progression in patients with type 2 diabetes and CKD, reducing the composite of sustained eGFR decline, kidney failure, and renal or cardiovascular death. The trial was stopped early for efficacy, establishing GLP-1 receptor agonists as a new renoprotective therapy alongside SGLT2 inhibitors.

Plozasiran (ARO-APOC3) for Severe Hypertriglyceridemia

The SHASTA-2 Randomized Clinical Trial.

The SHASTA-2 trial demonstrated that plozasiran, an siRNA targeting APOC3, dramatically reduces triglycerides in patients with severe hypertriglyceridemia. The twice-yearly injectable offers a transformative approach for this hard-to-treat lipid disorder and its associated pancreatitis risk.

Revisiting Race and the Benefit of RAS Blockade in Heart Failure

A Meta-Analysis of Randomized Clinical Trials.

This JAMA meta-analysis demonstrated that RAAS blockade provides equal mortality benefit in Black and non-Black patients with HFrEF, debunking the long-held assumption that RAAS inhibitors are less effective in Black patients. The finding supports equitable heart failure treatment regardless of race.

Invasive vs. conservative management of older patients with non-ST-elevation acute coronary syndrome

individual patient data meta-analysis.

This individual patient data meta-analysis confirmed that early invasive management reduces MI and repeat revascularization in older patients with NSTE-ACS compared with conservative management. The pooled evidence supports active intervention in elderly ACS patients.

Self-Expanding or Balloon-Expandable TAVR in Patients with a Small Aortic Annulus.

The SMART trial showed that balloon-expandable TAVR achieved significantly better hemodynamic performance than self-expanding TAVR in patients with a small aortic annulus. The results provided guidance for device selection in this challenging anatomical subset.

Sodium-Glucose Cotransporter-2 Inhibitors and Major Adverse Cardiovascular Outcomes

A SMART-C Collaborative Meta-Analysis.

This SMART-C collaborative meta-analysis of all major SGLT2 inhibitor trials confirmed that the class reduces heart failure hospitalization and kidney outcomes across all patient populations, while MACE reduction was primarily seen in patients with type 2 diabetes and atherosclerotic disease. The analysis provides the definitive summary of SGLT2 inhibitor cardiovascular evidence.

Pulmonary arterial hypertension treatment

an individual participant data network meta-analysis.

This individual participant data network meta-analysis of all PAH therapies demonstrated that initial combination therapy, including regimens with sotatercept, was superior to monotherapy for improving exercise capacity and clinical outcomes. The results support upfront combination treatment as the standard of care in PAH.

Intensive Ambulance-Delivered Blood-Pressure Reduction in Hyperacute Stroke.

This NEJM trial evaluated intensive ambulance-delivered blood pressure reduction in the hyperacute stroke phase, before distinction between ischemic and hemorrhagic subtypes. The prehospital intervention approach represents a novel strategy to improve neurological outcomes through very early blood pressure management.

Andexanet for Factor Xa Inhibitor-Associated Acute Intracerebral Hemorrhage.

The ANNEXA-I trial demonstrated that andexanet alfa, a factor Xa inhibitor reversal agent, significantly reduced hematoma expansion compared with usual care in patients with acute intracerebral hemorrhage while taking factor Xa inhibitors. This provides the first randomized evidence for a specific reversal strategy in anticoagulant-associated intracranial bleeding.

Olezarsen for Hypertriglyceridemia in Patients at High Cardiovascular Risk.

This NEJM trial showed that olezarsen reduced triglycerides by more than 50% in patients with hypertriglyceridemia and high cardiovascular risk. Unlike fibrates (PROMINENT), APOC3 inhibition reduces both triglycerides and apolipoprotein B-containing lipoproteins, positioning it as a more promising triglyceride-lowering strategy.

Olezarsen, Acute Pancreatitis, and Familial Chylomicronemia Syndrome.

This NEJM trial demonstrated that olezarsen, an antisense oligonucleotide targeting APOC3, dramatically reduced triglyceride levels and virtually eliminated acute pancreatitis episodes in patients with familial chylomicronemia syndrome. The results represent a transformative therapy for this severe, previously intractable genetic condition.

Intravascular ultrasound-guided versus angiography-guided percutaneous coronary intervention in acute coronary syndromes (IVUS-ACS)

a two-stage, multicentre, randomised trial.

The IVUS-ACS trial showed that IVUS-guided PCI significantly reduced target vessel failure compared with angiography-guided PCI in patients with acute coronary syndromes. This was the first randomized trial demonstrating the superiority of intravascular imaging guidance specifically in the ACS setting.

Ticagrelor alone versus ticagrelor plus aspirin from month 1 to month 12 after percutaneous coronary intervention in patients with acute coronary syndromes (ULTIMATE-DAPT)

a randomised, placebo-controlled, double-blind clinical trial.

This Lancet trial confirmed that ticagrelor monotherapy after 1 month of DAPT in ACS patients reduces bleeding without increasing ischemic events, adding to the robust evidence for early aspirin discontinuation in P2Y12-based antiplatelet strategies.

Preventive percutaneous coronary intervention versus optimal medical therapy alone for the treatment of vulnerable atherosclerotic coronary plaques (PREVENT)

a multicentre, open-label, randomised controlled trial.

The PREVENT trial demonstrated that preventive PCI of vulnerable atherosclerotic plaques identified by intravascular imaging (IVUS/OCT) reduced future coronary events compared with optimal medical therapy alone. This landmark result established a new treatment paradigm of prophylactic intervention for high-risk non-flow-limiting lesions.

Apolipoprotein A1 Infusions and Cardiovascular Outcomes after Acute Myocardial Infarction.

The AEGIS-II trial showed that infusion of recombinant apolipoprotein A1 (CSL112) after acute MI did not reduce the risk of MACE compared with placebo. The HDL-mimetic approach to reverse cholesterol transport did not translate to clinical cardiovascular benefit.

Ticagrelor or Clopidogrel Monotherapy vs Dual Antiplatelet Therapy After Percutaneous Coronary Intervention

A Systematic Review and Patient-Level Meta-Analysis.

This patient-level meta-analysis confirmed that P2Y12 inhibitor monotherapy (ticagrelor or clopidogrel) after a short course of DAPT reduces major bleeding compared with standard 12-month DAPT without increasing ischemic events. The pooled evidence definitively supports de-escalation to single antiplatelet therapy.

Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction

a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials.

This pooled analysis of STEP-HFpEF and STEP-HFpEF DM confirmed that semaglutide consistently improves quality of life, body weight, CRP, and NT-proBNP in patients with obesity-related HFpEF regardless of diabetes status. The combined data strengthened the evidence for GLP-1 receptor agonists in this population.

FFR-Guided Complete or Culprit-Only PCI in Patients with Myocardial Infarction.

The FRAME-AMI trial showed that FFR-guided complete revascularization of nonculprit lesions resulted in fewer stent implantations with comparable clinical outcomes versus routine angiography-guided complete PCI in patients with STEMI and multivessel disease. FFR guidance may reduce overtreatment without compromising safety.

Empagliflozin after Acute Myocardial Infarction.

The DAPA-MI trial showed that empagliflozin after acute MI in patients without heart failure or diabetes did not significantly improve the hierarchical composite of cardiovascular outcomes. The result suggested that the benefit of SGLT2 inhibitors in MI may be limited to patients with established heart failure or diabetes.

Beta-Blockers after Myocardial Infarction and Preserved Ejection Fraction.

The ABYSS trial showed that long-term beta-blocker therapy after myocardial infarction in patients with preserved left ventricular ejection fraction did not reduce the composite of death, MI, or stroke. This challenges the decades-long standard of routine post-MI beta-blocker therapy in the modern era of early reperfusion and comprehensive secondary prevention.

Microaxial Flow Pump or Standard Care in Infarct-Related Cardiogenic Shock.

The DanGer Shock trial demonstrated that the Impella CP microaxial flow pump significantly reduced 180-day all-cause mortality compared with standard care in patients with STEMI-related cardiogenic shock. This is the first positive randomized trial of a percutaneous mechanical circulatory support device in cardiogenic shock.

Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes.

The STEP-HFpEF-DM trial demonstrated that semaglutide 2.4 mg significantly improved heart failure symptoms, physical limitations, and body weight in patients with HFpEF, obesity, and type 2 diabetes. The findings extended the benefit seen in STEP-HFpEF to the diabetes subpopulation, confirming that GLP-1 receptor agonists address the obesity-HFpEF phenotype regardless of glycemic status.

2024 ACC Expert Consensus Decision Pathway for Treatment of Heart Failure With Reduced Ejection Fraction

A Report of the American College of Cardiology Solution Set Oversight Committee.

The 2024 ACC Expert Consensus for HFrEF endorsed simultaneous initiation of four-pillar therapy (SGLT2 inhibitor, ARNI, beta-blocker, MRA) rather than sequential titration, with practical algorithms for rapid optimization, including in-hospital initiation during heart failure admissions.

Transcatheter or surgical aortic valve implantation

10-year outcomes of the NOTION trial.

The 10-year NOTION results showed comparable survival between TAVR and surgical aortic valve replacement in low-risk patients, though more TAVR patients required reintervention for valve degeneration. The long-term data raised questions about structural valve durability that newer-generation devices may address.

Direct Oral Anticoagulants for Stroke Prevention in Patients With Device-Detected Atrial Fibrillation

A Study-Level Meta-Analysis of the NOAH-AFNET 6 and ARTESiA Trials.

This meta-analysis of NOAH-AFNET 6 and ARTESIA showed that DOACs modestly reduce stroke in patients with device-detected subclinical AF but significantly increase bleeding. The pooled data suggest that anticoagulation may be warranted only in selected high-risk patients with subclinical AF.

Intravascular imaging-guided coronary drug-eluting stent implantation

an updated network meta-analysis.

This updated Lancet network meta-analysis confirmed that intravascular imaging-guided DES implantation (either IVUS or OCT) is superior to angiography-guided PCI for reducing cardiovascular death, MI, and stent thrombosis. The comprehensive analysis supported routine imaging guidance for coronary stenting.

Impact of Bempedoic Acid on Total Cardiovascular Events

A Prespecified Analysis of the CLEAR Outcomes Randomized Clinical Trial.

This CLEAR Outcomes analysis of total cardiovascular events (including recurrent) showed that bempedoic acid significantly reduces the total burden of cardiovascular events in statin-intolerant patients, with greater absolute benefit than suggested by first-event analysis alone.

An Aspirin-Free Versus Dual Antiplatelet Strategy for Coronary Stenting

STOPDAPT-3 Randomized Trial.

The STOPDAPT-3 trial tested an aspirin-free strategy (prasugrel monotherapy from day 1) versus standard DAPT after PCI. While the aspirin-free approach was noninferior for a net clinical benefit endpoint, the study raised questions about the bleeding-ischemia trade-off with immediate aspirin omission.

Stopping Aspirin Within 1 Month After Stenting for Ticagrelor Monotherapy in Acute Coronary Syndrome

The T-PASS Randomized Noninferiority Trial.

The T-PASS trial showed that stopping aspirin within 1 month after DES implantation for ticagrelor monotherapy in ACS patients was noninferior to 12-month DAPT for ischemic events and reduced major bleeding. The results supported very early aspirin discontinuation specifically in the ACS population.

Safety and Efficacy of Ticagrelor Monotherapy in Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention

An Individual Patient Data Meta-Analysis of TWILIGHT and TICO Randomized Trials.

This individual patient data meta-analysis confirmed that early aspirin cessation with ticagrelor monotherapy after ACS and PCI is safe with significantly less bleeding, without increasing the risk of ischemic events. The pooled patient-level evidence provides the strongest support for this de-escalation strategy.

Implantable Hemodynamic Monitors Improve Survival in Patients With Heart Failure and Reduced Ejection Fraction.

This analysis demonstrated that implantable pulmonary artery pressure monitors not only reduce heart failure hospitalization but also improve survival in patients with HFrEF. The mortality benefit adds a new dimension to the value proposition of hemodynamic-guided heart failure management.

Long-Term Outcomes of Resynchronization-Defibrillation for Heart Failure.

The RAFT trial 14-year follow-up showed that CRT-D provides sustained survival benefit over ICD alone in patients with HFrEF and wide QRS. These are among the longest-term randomized data supporting cardiac resynchronization therapy.

Apixaban for Stroke Prevention in Subclinical Atrial Fibrillation.

The ARTESIA trial showed that apixaban reduced the risk of stroke and systemic embolism by 37% compared with aspirin in patients with subclinical atrial fibrillation detected by implanted cardiac devices, but at the cost of increased major bleeding. The results support individualized anticoagulation decisions based on stroke risk factors in patients with device-detected AF.

2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation

A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

The 2023 ACC/AHA/ACCP/HRS AF guideline (JACC edition) provides comprehensive updated recommendations for atrial fibrillation, including a new staging classification, early rhythm-control strategy, catheter ablation as first-line therapy in selected patients, and integrated management of AF risk factors including obesity.

2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation

A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

The 2023 ACC/AHA/ACCP/HRS atrial fibrillation guideline introduced a new four-stage classification system (stages 1–4), emphasized early rhythm control, endorsed catheter ablation as a first-line option for selected patients, and highlighted weight management as a disease-modifying intervention. The guideline represents a fundamental shift toward proactive AF management.

Restrictive or Liberal Transfusion Strategy in Myocardial Infarction and Anemia.

The REALITY trial demonstrated that a restrictive transfusion strategy (hemoglobin threshold <8 g/dL) was noninferior to a liberal strategy (<10 g/dL) for the composite of death, MI, stroke, or emergency revascularization in patients with acute MI and anemia. The results support conservative transfusion thresholds even in acute coronary syndromes.

A Placebo-Controlled Trial of Percutaneous Coronary Intervention for Stable Angina.

ORBITA-2, a double-blind, placebo-controlled trial in patients with stable angina who were not receiving antianginal medications, showed that PCI significantly improved angina symptoms compared with a sham procedure. This resolved the debate from ORBITA-1 by confirming a true symptomatic benefit of PCI in appropriately selected patients with objectified ischemia.

Efficacy of ferric carboxymaltose in heart failure with iron deficiency

an individual patient data meta-analysis.

This individual patient data meta-analysis of all ferric carboxymaltose trials in heart failure confirmed that IV iron reduces heart failure hospitalization and cardiovascular death, with the most robust benefit in reducing recurrent hospitalizations. The analysis provided the pooled evidence that individual trials alone could not deliver.

Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes.

The SELECT trial demonstrated that semaglutide 2.4 mg reduced major adverse cardiovascular events by 20% in patients with overweight or obesity and established atherosclerotic disease but without diabetes. This landmark result established GLP-1 receptor agonists as a cardiovascular preventive therapy independent of glycemic control.

Zibotentan in combination with dapagliflozin compared with dapagliflozin in patients with chronic kidney disease (ZENITH-CKD)

a multicentre, randomised, active-controlled, phase 2b, clinical trial.

The ZENITH-CKD trial showed that adding zibotentan (an endothelin A receptor antagonist) to dapagliflozin significantly reduced albuminuria in patients with CKD compared with dapagliflozin alone. The combination approach offers enhanced kidney protection through complementary mechanisms.

Transcatheter Aortic-Valve Replacement in Low-Risk Patients at Five Years.

The 5-year PARTNER 3 follow-up confirmed that outcomes after TAVR remained comparable to surgical aortic valve replacement in low-risk patients with severe aortic stenosis. Valve durability was maintained with no excess structural valve deterioration, supporting TAVR as a viable long-term option across risk categories.

Pulsed Field or Conventional Thermal Ablation for Paroxysmal Atrial Fibrillation.

The ADVENT trial demonstrated that pulsed field ablation was noninferior to conventional thermal ablation (radiofrequency or cryoablation) for the treatment of paroxysmal atrial fibrillation, with a comparable safety profile. This established PFA as a safe and effective tissue-selective alternative for pulmonary vein isolation.

Traditional Chinese Medicine Compound (Tongxinluo) and Clinical Outcomes of Patients With Acute Myocardial Infarction

The CTS-AMI Randomized Clinical Trial.

The CTS-AMI mega-trial demonstrated that Tongxinluo, a traditional Chinese medicine compound, significantly reduced cardiovascular events after STEMI when added to guideline-directed therapy. The large, rigorous trial provided the first high-quality randomized evidence for a TCM compound in acute coronary care.

Optical Coherence Tomography-Guided versus Angiography-Guided PCI.

The ILUMIEN IV trial showed that OCT-guided PCI improved the procedural quality (minimum stent area) but did not significantly reduce the clinical composite of cardiac death or MI compared with angiography-guided PCI at 2 years. The study highlighted the gap between procedural optimization and hard clinical outcomes.

OCT or Angiography Guidance for PCI in Complex Bifurcation Lesions.

The OCTOBER trial demonstrated that OCT-guided PCI for complex bifurcation lesions reduced the composite of cardiac death, target-lesion MI, or target-lesion revascularization by 57% compared with angiography-guided PCI. This established OCT as a valuable guidance tool specifically for bifurcation intervention.

Orthostatic Hypotension, Hypertension Treatment, and Cardiovascular Disease

An Individual Participant Meta-Analysis.

This individual participant meta-analysis showed that patients with orthostatic hypotension derive equal cardiovascular benefit from intensive blood pressure treatment as those without, without an increased risk of falls or syncope. The results argued against withholding aggressive treatment due to orthostatic hypotension.

Optical Coherence Tomography-Guided or Intravascular Ultrasound-Guided Percutaneous Coronary Intervention

The OCTIVUS Randomized Clinical Trial.

The OCTIVUS trial demonstrated that OCT-guided PCI was noninferior to IVUS-guided PCI for clinical outcomes. The result established OCT and IVUS as interchangeable intravascular imaging modalities for guiding coronary intervention.

Venoarterial extracorporeal membrane oxygenation in patients with infarct-related cardiogenic shock

an individual patient data meta-analysis of randomised trials.

This individual patient data meta-analysis confirmed that VA-ECMO does not improve survival in patients with infarct-related cardiogenic shock, with pooled data from randomized trials showing no mortality benefit but increased limb complications. The analysis definitively discouraged routine ECMO use in this setting.

Timing of Complete Revascularization with Multivessel PCI for Myocardial Infarction.

The MULTISTARS AMI trial showed that immediate complete revascularization during the index primary PCI procedure was superior to staged revascularization within 45 days for reducing cardiovascular death or MI in patients with STEMI and multivessel disease. The results support a one-stop-shop approach when feasible.

Catheter Ablation in End-Stage Heart Failure with Atrial Fibrillation.

The CASTLE-HTx trial demonstrated that catheter ablation for atrial fibrillation in patients with end-stage heart failure (on LVAD or transplant waiting list) dramatically improved survival, with a 44% relative reduction in the composite of death, LVAD implantation, or urgent heart transplantation. The results extend the benefit of AF ablation to the most severely ill heart failure patients.

Extracorporeal Life Support in Infarct-Related Cardiogenic Shock.

The ECLS-SHOCK trial showed that routine extracorporeal membrane oxygenation (ECMO) did not improve 30-day survival compared with standard care in patients with infarct-related cardiogenic shock. This large, definitive trial ended the enthusiasm for routine ECLS in MI-associated cardiogenic shock.

Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality.

This PURE study analysis demonstrated that five modifiable risk factors (hypertension, dyslipidemia, diabetes, obesity, and smoking) account for the majority of cardiovascular disease and mortality worldwide, with regional variation in their relative contributions. The individual-level data across 21 countries provided the definitive global picture of attributable cardiovascular risk.

Estimated Glomerular Filtration Rate, Albuminuria, and Adverse Outcomes

An Individual-Participant Data Meta-Analysis.

This mega-scale individual participant data meta-analysis confirmed that low eGFR and albuminuria independently and additively predict cardiovascular events and mortality. The combined assessment provides superior risk stratification compared with either marker alone.

Mineralocorticoid receptor antagonists with sodium-glucose co-transporter-2 inhibitors in heart failure

a meta-analysis.

This meta-analysis showed that combining an MRA with an SGLT2 inhibitor in heart failure provides additive reductions in cardiovascular death and heart failure hospitalization beyond either drug class alone. The findings support the four-pillar approach including dual neurohormonal and metabolic modulation.

Efficacy of pulmonary artery pressure monitoring in patients with chronic heart failure

a meta-analysis of three randomized controlled trials.

This meta-analysis of CHAMPION, GUIDE-HF, and MONITOR-HF confirmed that implantable pulmonary artery pressure monitoring significantly reduces heart failure hospitalization in chronic heart failure. The pooled evidence across three continents supported the clinical utility of hemodynamic monitoring.

Anticoagulation with Edoxaban in Patients with Atrial High-Rate Episodes.

The NOAH-AFNET 6 trial found that edoxaban did not significantly reduce cardiovascular events compared with placebo in patients with device-detected atrial high-rate episodes (AHREs) but without clinical atrial fibrillation, while increasing major bleeding. The results do not support routine anticoagulation for subclinical atrial arrhythmias detected by cardiac devices.

Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity.

The STEP-HFpEF trial showed that weekly semaglutide 2.4 mg in patients with HFpEF and obesity dramatically improved heart failure symptoms, physical limitations, and quality of life, with a mean 13% body weight reduction. This landmark result established GLP-1 receptor agonists as a transformative therapy for the obesity-HFpEF phenotype.

Fractional Flow Reserve-Guided PCI or Coronary Bypass Surgery for 3-Vessel Coronary Artery Disease

3-Year Follow-Up of the FAME 3 Trial.

Three-year FAME 3 follow-up confirmed that FFR-guided PCI did not achieve noninferiority versus CABG for three-vessel coronary disease, with CABG maintaining lower rates of revascularization and MI. The extended data reinforced CABG as the standard for complex multivessel disease.

Ferric Carboxymaltose in Heart Failure with Iron Deficiency.

The HEART-FID trial showed that intravenous ferric carboxymaltose in patients with HFrEF and iron deficiency did not significantly improve the hierarchical composite of death, heart failure hospitalization, and 6-minute walk distance. The neutral result contrasted with positive findings from AFFIRM-AHF and IRONMAN.

Complete or Culprit-Only PCI in Older Patients with Myocardial Infarction.

The FIRE trial demonstrated that complete revascularization reduced cardiovascular death or MI compared with culprit-only PCI in patients aged 75 or older with MI and multivessel disease. The results extended the benefit of complete revascularization to the elderly population previously excluded from major trials.

Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity.

This NEJM phase 2 trial demonstrated that orforglipron, an oral nonpeptide GLP-1 receptor agonist, produced dose-dependent weight loss of up to 14.7% in adults with obesity. The results positioned oral GLP-1 therapy as a practical alternative to injectable formulations for obesity treatment.

Pitavastatin to Prevent Cardiovascular Disease in HIV Infection.

The REPRIEVE trial demonstrated that pitavastatin reduced major cardiovascular events by 35% in people living with HIV who had low-to-moderate cardiovascular risk. The trial was stopped early for efficacy, providing the first definitive evidence for statin therapy in primary cardiovascular prevention among HIV-infected individuals.

Fixed dose combination therapies in primary cardiovascular disease prevention in different groups

an individual participant meta-analysis.

This individual participant data meta-analysis from three randomized trials confirmed that fixed-dose combination therapy (polypill) reduces cardiovascular events in primary prevention across different age groups. The consistent benefit supports the polypill strategy as a population-level intervention.

Sacubitril/valsartan in heart failure with mildly reduced or preserved ejection fraction

a pre-specified participant-level pooled analysis of PARAGLIDE-HF and PARAGON-HF.

This participant-level pooled analysis of PARAGON-HF, PARADIGM-HF, and PARAGLIDE-HF confirmed that sacubitril-valsartan reduces NT-proBNP and heart failure events in patients with HFmrEF and HFpEF (EF ≥40%), particularly those with lower LVEF within this range.

Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes

a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA.

This Lancet phase 2 trial of retatrutide, a triple GIP/GLP-1/glucagon receptor agonist, demonstrated up to 24% weight loss and dramatic HbA1c improvement in patients with type 2 diabetes. The results surpassed those of dual incretin agonists, establishing triple agonism as the next frontier in metabolic therapeutics.

Atorvastatin for Anthracycline-Associated Cardiac Dysfunction

The STOP-CA Randomized Clinical Trial.

The STOP-CA trial showed that atorvastatin significantly attenuated the decline in left ventricular ejection fraction in patients receiving anthracycline chemotherapy. The result established statins as a potential cardioprotective strategy during cancer treatment.

GLP-1 Receptor Agonist Therapy With and Without SGLT2 Inhibitors in Patients With Type 2 Diabetes.

This analysis demonstrated that GLP-1 receptor agonists and SGLT2 inhibitors provide complementary cardiovascular benefits when used together in type 2 diabetes, with additive reductions in MACE and heart failure events. The findings support dual cardiometabolic therapy in eligible patients.

Zilebesiran, an RNA Interference Therapeutic Agent for Hypertension.

This first-in-human study of zilebesiran, an RNA interference agent targeting hepatic angiotensinogen, demonstrated sustained blood pressure reduction for up to 24 weeks after a single subcutaneous injection. The findings represent a potential paradigm shift toward ultra-long-acting antihypertensive therapy requiring only biannual dosing.

Phase 1 Trial of Antibody NI006 for Depletion of Cardiac Transthyretin Amyloid.

This first-in-human phase 1 trial showed that NI006, a monoclonal antibody targeting transthyretin amyloid deposits, can reduce cardiac amyloid burden in patients with ATTR cardiomyopathy. This represents the first therapeutic approach aimed at clearing existing amyloid deposits rather than just preventing new deposition.

Cardiovascular Safety of Testosterone-Replacement Therapy.

The TRAVERSE trial demonstrated that testosterone-replacement therapy in middle-aged and older men with hypogonadism and cardiovascular risk factors did not increase the incidence of major adverse cardiovascular events. This large safety trial resolved decades of uncertainty about the cardiovascular risks of testosterone therapy.

P2Y12 Inhibitor or Aspirin Monotherapy for Secondary Prevention of Coronary Events.

This meta-analysis confirmed that P2Y12 inhibitor monotherapy is superior to aspirin for long-term secondary prevention of coronary events, with fewer ischemic events (especially stroke) and no increase in bleeding. The data support replacing aspirin with clopidogrel as the default post-DAPT agent.

The third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT3)

an international, stepped wedge cluster randomised controlled trial.

The INTERACT3 trial showed that a goal-directed care bundle with early intensive blood pressure lowering improved functional outcomes in patients with acute intracerebral hemorrhage. The pragmatic, cluster-randomized design demonstrated that structured care protocols can improve outcomes at scale.

Early versus Later Anticoagulation for Stroke with Atrial Fibrillation.

The ELAN trial showed that early initiation of DOACs (within 48 hours for mild stroke, within 6–7 days for moderate stroke) after ischemic stroke in patients with atrial fibrillation was safe and associated with fewer recurrent strokes compared with later initiation. The results support a move toward earlier anticoagulation in this high-risk population.

Effect of SGLT2 Inhibitors on Cardiovascular Outcomes Across Various Patient Populations.

This comprehensive JACC review summarized the effects of SGLT2 inhibitors across all studied populations — HFrEF, HFpEF, CKD, and type 2 diabetes — providing a unified overview of their cardiovascular and renal benefits and positioning them as foundational cardiometabolic therapy.

Remote haemodynamic monitoring of pulmonary artery pressures in patients with chronic heart failure (MONITOR-HF)

a randomised clinical trial.

The MONITOR-HF trial confirmed that remote pulmonary artery pressure monitoring (CardioMEMS) improved quality of life and reduced heart failure hospitalization in European patients with chronic heart failure treated with contemporary guideline-directed therapy. The results extended the evidence from the US-based CHAMPION trial.

Treatment of Gestational Diabetes Mellitus Diagnosed Early in Pregnancy.

This NEJM trial demonstrated that treatment of gestational diabetes diagnosed before 20 weeks of pregnancy improved neonatal outcomes, with fewer macrosomic infants and less need for neonatal intensive care. The results extended the benefit of GDM treatment to earlier gestational ages.

Uptitrating Treatment After Heart Failure Hospitalization Across the Spectrum of Left Ventricular Ejection Fraction.

This STRONG-HF subanalysis showed that rapid up-titration of guideline-directed therapy after heart failure hospitalization was effective across the entire ejection fraction spectrum, including patients with HFpEF. The results expanded the aggressive post-discharge optimization approach beyond HFrEF.

Direct Oral Anticoagulants Versus Warfarin Across the Spectrum of Kidney Function

Patient-Level Network Meta-Analyses From COMBINE AF.

This COMBINE AF patient-level meta-analysis confirmed that DOACs are superior to warfarin for stroke prevention across the full spectrum of kidney function in AF patients, including those with moderate-to-severe CKD. The data address a key uncertainty in anticoagulation management.

Efficacy and Safety of Low-Dose Triple and Quadruple Combination Pills vs Monotherapy, Usual Care, or Placebo for the Initial Management of Hypertension

A Systematic Review and Meta-analysis.

This meta-analysis confirmed that low-dose triple and quadruple combination antihypertensive pills are more effective than monotherapy for initial blood pressure treatment, with better control rates and comparable tolerability. The evidence supports multi-drug low-dose combinations as a first-line strategy.

Five-Year Follow-up after Transcatheter Repair of Secondary Mitral Regurgitation.

The 5-year COAPT follow-up confirmed durable benefit of transcatheter mitral valve repair with MitraClip in patients with heart failure and severe secondary mitral regurgitation, with sustained reductions in mortality and heart failure hospitalization compared with medical therapy alone.

A vein bypass first versus a best endovascular treatment first revascularisation strategy for patients with chronic limb threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal revascularisation procedure to restore limb perfusion (BASIL-2)

an open-label, randomised, multicentre, phase 3 trial.

The BEST-CLI trial demonstrated that vein bypass surgery was superior to endovascular therapy as the initial revascularization strategy for patients with chronic limb-threatening ischemia when a good-quality great saphenous vein was available. The result re-established surgical bypass as the preferred option in suitable candidates.

Transcatheter Repair for Patients with Tricuspid Regurgitation.

The TRILUMINATE trial demonstrated that transcatheter edge-to-edge repair (TriClip) for severe tricuspid regurgitation was safe and significantly reduced regurgitation severity, though it did not meet the primary composite endpoint of death or tricuspid-related surgery. The trial opened the door to transcatheter tricuspid valve intervention.

2023 ACC Expert Consensus Decision Pathway on Management of Heart Failure With Preserved Ejection Fraction

A Report of the American College of Cardiology Solution Set Oversight Committee.

The 2023 ACC Expert Consensus provided a structured decision pathway for HFpEF management, positioning SGLT2 inhibitors as a cornerstone therapy alongside diuretics for volume management, GLP-1 receptor agonists for obesity, and targeted treatment of comorbidities.

Intravascular Imaging-Guided or Angiography-Guided Complex PCI.

The RENOVATE-COMPLEX-PCI trial showed that intravascular imaging-guided PCI (using IVUS or OCT) significantly reduced the composite of cardiac death, MI, or revascularization compared with angiography-guided PCI in patients with complex coronary lesions. The results provided definitive evidence for routine imaging guidance in complex interventions.

Phase 2b Randomized Trial of the Oral PCSK9 Inhibitor MK-0616.

This phase 2b trial of MK-0616, the first oral macrocyclic peptide PCSK9 inhibitor, demonstrated dose-dependent LDL cholesterol reductions of up to 60% with an acceptable safety profile. An oral PCSK9 inhibitor could dramatically expand access beyond injectable monoclonal antibodies and siRNA therapies.

Phase 3 Trial of Sotatercept for Treatment of Pulmonary Arterial Hypertension.

The STELLAR trial demonstrated that sotatercept, a first-in-class activin receptor fusion protein, dramatically improved exercise capacity, hemodynamics, and WHO functional class in patients with pulmonary arterial hypertension on background therapy. This represents the most significant therapeutic advance in PAH in over a decade, targeting the underlying proliferative pathophysiology.

Association Between Achieved Low-Density Lipoprotein Cholesterol Levels and Long-Term Cardiovascular and Safety Outcomes

An Analysis of FOURIER-OLE.

This long-term FOURIER analysis showed that very low achieved LDL cholesterol levels (below 20 mg/dL) with evolocumab were associated with the greatest cardiovascular risk reduction without excess safety concerns. The data supported pushing LDL targets as low as achievable.

Dual antiplatelet therapy de-escalation in acute coronary syndrome

an individual patient meta-analysis.

This individual patient data meta-analysis confirmed that de-escalation from potent P2Y12 inhibitors to clopidogrel after the acute phase of ACS safely reduces bleeding without increasing ischemic events. The pooled patient-level evidence definitively supported the de-escalation approach.

Inflammation and cholesterol as predictors of cardiovascular events among patients receiving statin therapy

a collaborative analysis of three randomised trials.

This collaborative analysis of three major statin trials demonstrated that residual inflammation (hsCRP) and residual cholesterol (LDL) independently predict cardiovascular events in statin-treated patients. Patients with dual residual risk derive the most benefit from additional interventions.

Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients.

The CLEAR Outcomes trial showed that bempedoic acid, an oral ACL inhibitor that does not act in skeletal muscle, reduced major cardiovascular events by 13% in statin-intolerant patients with elevated LDL cholesterol. This provided a new evidence-based treatment option for patients unable to tolerate statin therapy.

Heterogeneity in Blood Pressure Response to 4 Antihypertensive Drugs

A Randomized Clinical Trial.

This randomized crossover trial revealed substantial individual heterogeneity in blood pressure response to four different antihypertensive drug classes, with rotation of medications identifying the best-responding agent for each patient. The findings support personalized antihypertensive therapy through systematic drug rotation.

Immediate versus staged complete revascularisation in patients presenting with acute coronary syndrome and multivessel coronary disease (BIOVASC)

a prospective, open-label, non-inferiority, randomised trial.

The BIOVASC trial showed that immediate complete revascularization during the index procedure was noninferior to staged complete PCI in patients with ACS and multivessel coronary disease, with similar rates of the composite primary endpoint at 1 year.

Treat-to-Target or High-Intensity Statin in Patients With Coronary Artery Disease

A Randomized Clinical Trial.

The LODESTAR trial showed that a treat-to-target approach (targeting LDL <70 mg/dL with dose adjustment) was noninferior to fixed high-intensity statin therapy for cardiovascular outcomes in patients with coronary artery disease. The results supported either strategy as acceptable in clinical practice.

Effectiveness of a non-physician community health-care provider-led intensive blood pressure intervention versus usual care on cardiovascular disease (CRHCP)

an open-label, blinded-endpoint, cluster-randomised trial.

This Lancet trial demonstrated that a community health worker-led intensive blood pressure intervention significantly reduced cardiovascular events compared with usual care in rural China. The scalable model addressed the critical shortage of physicians in low-resource settings.

Endovascular Ultrasound Renal Denervation to Treat Hypertension

The RADIANCE II Randomized Clinical Trial.

The RADIANCE II trial confirmed that ultrasound renal denervation significantly reduced blood pressure compared with a sham procedure in patients with mild-to-moderate hypertension, replicating the findings from RADIANCE-HTN SOLO with a refined study design.

Incidental Coronary Artery Calcium

Opportunistic Screening of Previous Nongated Chest Computed Tomography Scans to Improve Statin Rates (NOTIFY-1 Project).

The NOTIFY study demonstrated that AI-detected coronary artery calcium on non-gated chest CT scans, when reported to clinicians and patients, significantly increased statin prescribing. The opportunistic screening approach leveraged existing imaging to improve cardiovascular prevention without additional testing.

Catheter ablation improves cardiovascular outcomes in patients with atrial fibrillation and heart failure

a meta-analysis of randomized controlled trials.

This meta-analysis of randomized trials confirmed that catheter ablation for atrial fibrillation in heart failure patients significantly improves cardiovascular outcomes, including reductions in mortality and heart failure hospitalization. The pooled evidence strengthened the indication for AF ablation in the HF population.

Extracorporeal Membrane Oxygenation in the Therapy of Cardiogenic Shock

Results of the ECMO-CS Randomized Clinical Trial.

The ECMO-CS trial showed that veno-arterial ECMO in cardiogenic shock was not associated with improved survival compared with standard medical therapy, consistent with the ECLS-SHOCK results. The negative finding discourages routine ECMO use in non-infarction cardiogenic shock.

Phase 2 Trial of Baxdrostat for Treatment-Resistant Hypertension.

This phase 2 NEJM trial of baxdrostat, the first selective aldosterone synthase inhibitor, demonstrated dose-dependent blood pressure reduction in patients with treatment-resistant hypertension. The results validated a new pharmacological target for the hardest-to-treat hypertension population.

Combining loop with thiazide diuretics for decompensated heart failure

the CLOROTIC trial.

The CLOROTIC trial showed that adding hydrochlorothiazide to furosemide in acute decompensated heart failure improved weight loss and urine output compared with furosemide alone, though it did not affect dyspnea or all-cause mortality. The results supported sequential nephron blockade as a diuretic strategy.

Effect of Torsemide vs Furosemide After Discharge on All-Cause Mortality in Patients Hospitalized With Heart Failure

The TRANSFORM-HF Randomized Clinical Trial.

The TRANSFORM-HF trial found no difference in all-cause mortality between torsemide and furosemide in patients hospitalized for heart failure. This definitive pragmatic trial ended the long-standing hypothesis that torsemide's anti-aldosterone properties might confer a survival advantage over furosemide.

Cost-effectiveness of population screening for atrial fibrillation

the STROKESTOP study.

The STROKESTOP cost-effectiveness analysis showed that population-level screening for atrial fibrillation in 75-76-year-olds using intermittent ECG recordings is cost-effective, with favorable incremental cost per QALY gained. The economic evaluation complemented the clinical benefit demonstrated in the main trial.

Progression of Atrial Fibrillation after Cryoablation or Drug Therapy.

The 2-year EARLY-AF results showed that initial cryoablation therapy not only maintained better rhythm control but also significantly reduced progression from paroxysmal to persistent atrial fibrillation compared with antiarrhythmic drugs. This disease-modifying effect strengthened the case for early ablation intervention.

Empagliflozin in Patients with Chronic Kidney Disease.

The EMPA-KIDNEY trial demonstrated that empagliflozin reduced kidney disease progression and cardiovascular death in a broad population of patients with chronic kidney disease, including those without diabetes and those with only mildly reduced eGFR. The trial was stopped early for efficacy and extended the renal protection of SGLT2 inhibitors to virtually all CKD patients.

Effect of Catheter Ablation Using Pulmonary Vein Isolation With vs Without Posterior Left Atrial Wall Isolation on Atrial Arrhythmia Recurrence in Patients With Persistent Atrial Fibrillation

The CAPLA Randomized Clinical Trial.

The CAPLA trial showed that adding posterior left atrial wall isolation to standard pulmonary vein isolation did not significantly reduce AF recurrence in patients with persistent atrial fibrillation. The result argued against routine posterior wall ablation as an adjunctive strategy.

Prospective Association of Daily Steps With Cardiovascular Disease

A Harmonized Meta-Analysis.

This harmonized meta-analysis demonstrated a dose-response relationship between daily step count and cardiovascular disease risk, with as few as 2,000-3,000 steps per day providing measurable benefit. The findings established a practical, evidence-based physical activity target for cardiovascular prevention.

Aspirin Versus Clopidogrel for Long-Term Maintenance Monotherapy After Percutaneous Coronary Intervention

The HOST-EXAM Extended Study.

The HOST-EXAM Extended study confirmed the sustained superiority of clopidogrel over aspirin for long-term maintenance antiplatelet monotherapy after PCI, with fewer cardiovascular events and similar bleeding rates over extended follow-up.

Phase 2 Study of Aficamten in Patients With Obstructive Hypertrophic Cardiomyopathy.

This phase 2 study of aficamten, a next-generation cardiac myosin inhibitor, showed dose-dependent reduction of the LVOT gradient and symptom improvement in patients with obstructive hypertrophic cardiomyopathy. The results advanced aficamten toward phase 3 development as an alternative to mavacamten.

Comparative Effects of Low-Dose Rosuvastatin, Placebo, and Dietary Supplements on Lipids and Inflammatory Biomarkers.

This JACC study compared low-dose rosuvastatin with six popular dietary supplements (fish oil, cinnamon, garlic, turmeric, plant sterols, red yeast rice) for lipid and inflammatory biomarker effects. Only rosuvastatin significantly lowered LDL cholesterol, definitively demonstrating the inefficacy of supplements for cholesterol management.

Survival After Invasive or Conservative Management of Stable Coronary Disease.

Extended ISCHEMIA follow-up confirmed that an initial invasive strategy provided no survival benefit over conservative management in patients with stable coronary disease and moderate-to-severe ischemia. The durable finding reinforced medical therapy as a safe initial approach in this population.

Impact of empagliflozin on decongestion in acute heart failure

the EMPULSE trial.

This EMPULSE subanalysis showed that empagliflozin started during acute heart failure hospitalization significantly improved decongestion markers, including weight loss and hemoconcentration, supporting SGLT2 inhibitors as an adjunctive decongestion strategy.

Chlorthalidone vs. Hydrochlorothiazide for Hypertension-Cardiovascular Events.

This large pragmatic NEJM trial in 13,000 hypertensive veterans demonstrated that chlorthalidone was not superior to hydrochlorothiazide for preventing major cardiovascular events. The results challenged the assumption of chlorthalidone's superiority and supported continued use of either thiazide diuretic.

Blood pressure lowering and prevention of dementia

an individual patient data meta-analysis.

This individual patient data meta-analysis demonstrated that blood pressure lowering reduces the risk of incident dementia, with no evidence of a U-shaped relationship at lower blood pressure levels. The analysis provided the strongest evidence yet for blood pressure control as a dementia prevention strategy.

Intravenous ferric derisomaltose in patients with heart failure and iron deficiency in the UK (IRONMAN)

an investigator-initiated, prospective, randomised, open-label, blinded-endpoint trial.

The IRONMAN trial showed a trend toward reduced heart failure hospitalization and cardiovascular death with intravenous ferric derisomaltose in patients with heart failure and iron deficiency, though the primary endpoint did not reach statistical significance. COVID-19 pandemic disruptions affected enrollment and follow-up.

Apixaban for Patients With Atrial Fibrillation on Hemodialysis

A Multicenter Randomized Controlled Trial.

This first randomized trial of apixaban in AF patients on hemodialysis showed no significant improvement over usual care (mostly warfarin) for stroke prevention, with similar rates of bleeding and thrombotic events. The result highlighted the persistent evidence gap in anticoagulation for dialysis patients with AF.

Dual endothelin antagonist aprocitentan for resistant hypertension (PRECISION)

a multicentre, blinded, randomised, parallel-group, phase 3 trial.

The PRECISION trial showed that aprocitentan, a dual endothelin receptor antagonist, significantly reduced blood pressure in patients with resistant hypertension on triple therapy. This was the first positive phase 3 trial of an endothelin antagonist for systemic hypertension, opening a new mechanism of action for treatment-resistant blood pressure.

Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure (STRONG-HF)

a multinational, open-label, randomised, trial.

The STRONG-HF trial demonstrated that rapid, intensive up-titration of guideline-directed medical therapy (beta-blocker, RAAS inhibitor, MRA) within two weeks of hospital discharge for acute heart failure was safe and significantly reduced heart failure readmission and death compared with usual care. The study established early, aggressive optimization as the standard post-discharge approach.

LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes

a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial.

This phase 1b trial of a triple GIP/GLP-1/glucagon receptor agonist (retatrutide) demonstrated dramatic HbA1c reduction and weight loss in patients with type 2 diabetes. The triple agonism concept showed additive metabolic benefit beyond dual GIP/GLP-1 agonists.

Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk.

The PROMINENT trial showed that pemafibrate, a selective PPARα agonist, effectively lowered triglycerides but did not reduce cardiovascular events in patients with type 2 diabetes and elevated triglycerides despite statin therapy. This definitive negative result, together with earlier fibrate failures, largely closed the door on triglyceride lowering as a cardiovascular prevention strategy.

Everolimus-Eluting Stents or Bypass Surgery for Multivessel Coronary Artery Disease

Extended Follow-Up Outcomes of Multicenter Randomized Controlled BEST Trial.

This extended follow-up of multiple randomized trials comparing PCI with everolimus-eluting stents versus CABG for multivessel disease confirmed that CABG provides superior long-term outcomes, particularly for complex coronary anatomy. The results reinforced CABG as the preferred strategy for extensive multivessel disease.

Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes

collaborative meta-analysis of large placebo-controlled trials.

This collaborative meta-analysis of major SGLT2 inhibitor trials demonstrated that the kidney-protective effects of SGLT2 inhibition are independent of diabetes status and baseline kidney function. The findings support SGLT2 inhibitors as a universal renoprotective therapy across diverse CKD populations.

Small Interfering RNA to Reduce Lipoprotein(a) in Cardiovascular Disease.

The OCEAN(a)-DOSE trial demonstrated that olpasiran, a small interfering RNA targeting hepatic apolipoprotein(a) synthesis, reduced lipoprotein(a) levels by more than 95% in patients with established atherosclerotic cardiovascular disease. This represented the first pharmacological agent capable of near-complete Lp(a) elimination, opening a new therapeutic frontier.

Hospitalizations and Mortality in Patients With Secondary Mitral Regurgitation and Heart Failure

The COAPT Trial.

Long-term COAPT analysis confirmed that transcatheter edge-to-edge repair (MitraClip) durably reduces hospitalizations and mortality in patients with heart failure and severe secondary mitral regurgitation, with sustained benefit beyond the initial follow-up period.

Intensive blood pressure control after endovascular thrombectomy for acute ischaemic stroke (ENCHANTED2/MT)

a multicentre, open-label, blinded-endpoint, randomised controlled trial.

The ENCHANTED2/MT trial demonstrated that intensive blood pressure lowering to <120 mmHg after endovascular thrombectomy for acute ischemic stroke worsened functional outcomes compared with a higher target. The trial was stopped early for futility and potential harm.

Empagliflozin in acute myocardial infarction

the EMMY trial.

The EMMY trial showed that empagliflozin started after acute MI significantly reduced NT-proBNP levels and attenuated left ventricular remodeling compared with placebo. The results provided early evidence of SGLT2 inhibitor cardioprotection in the acute post-MI setting.

Patiromer for the management of hyperkalemia in heart failure with reduced ejection fraction

the DIAMOND trial.

The DIAMOND trial showed that patiromer effectively reduced serum potassium in patients with HFrEF, enabling more patients to reach target doses of RAAS inhibitors without hyperkalemia-related dose reductions. The results addressed a key barrier to optimal heart failure pharmacotherapy.

Cardiovascular outcomes in adults with hypertension with evening versus morning dosing of usual antihypertensives in the UK (TIME study)

a prospective, randomised, open-label, blinded-endpoint clinical trial.

The TIME trial showed that evening dosing of antihypertensive medications offered no cardiovascular benefit over morning dosing in hypertensive adults, definitively refuting the chronotherapy hypothesis. The pragmatic result simplified clinical practice by confirming that dosing time does not matter.

Blood-Pressure Targets in Comatose Survivors of Cardiac Arrest.

The BOX trial found no difference between a high (77 mmHg) versus low (63 mmHg) mean arterial pressure target in comatose survivors of out-of-hospital cardiac arrest. The result indicated that there is a broad acceptable blood pressure range in post-cardiac arrest intensive care.

Efficacy and Safety of Dapagliflozin According to Frailty in Patients With Heart Failure

A Prespecified Analysis of the DELIVER Trial.

This DELIVER subanalysis demonstrated that dapagliflozin provides similar relative benefit in frail and non-frail patients with HFpEF, with even greater absolute benefit in frail patients due to their higher baseline risk. The results supported SGLT2 inhibitor use regardless of frailty status.

Percutaneous Revascularization for Ischemic Left Ventricular Dysfunction.

The REVIVED-BCIS2 trial showed that PCI did not improve survival or left ventricular function compared with optimal medical therapy in patients with severe ischemic cardiomyopathy and viable myocardium. The result challenged the long-held assumption that revascularization improves outcomes in ischemic left ventricular dysfunction and supports a medical-therapy-first approach.

Allopurinol versus usual care in UK patients with ischaemic heart disease (ALL-HEART)

a multicentre, prospective, randomised, open-label, blinded-endpoint trial.

The ALL-HEART trial showed that allopurinol did not improve cardiovascular outcomes in patients with ischemic heart disease without gout, despite its theoretical benefits on endothelial function and oxidative stress. The large, pragmatic negative result argued against using allopurinol for cardiovascular prevention.

Early Versus Delayed Non-Vitamin K Antagonist Oral Anticoagulant Therapy After Acute Ischemic Stroke in Atrial Fibrillation (TIMING)

A Registry-Based Randomized Controlled Noninferiority Study.

The Swedish TIMING trial demonstrated that early NOAC initiation (within 4 days) after acute ischemic stroke in patients with AF was safe and noninferior to delayed start (5-10 days) for the composite of stroke, major bleeding, or death. The results supported a move toward earlier anticoagulation.

Dapagliflozin in Patients Recently Hospitalized With Heart Failure and Mildly Reduced or Preserved Ejection Fraction.

This DELIVER subanalysis confirmed that dapagliflozin is effective in patients recently hospitalized for heart failure with mildly reduced or preserved ejection fraction, with early benefit seen within weeks of treatment initiation. The data supported in-hospital SGLT2 inhibitor use in HFpEF.

2022 ACC Expert Consensus Decision Pathway on the Role of Nonstatin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk

A Report of the American College of Cardiology Solution Set Oversight Committee.

The 2022 ACC Expert Consensus updated the decision pathway for nonstatin lipid-lowering therapies, integrating evidence on bempedoic acid and inclisiran alongside ezetimibe and PCSK9 monoclonal antibodies. The document provided practical algorithms for escalating therapy to achieve LDL-cholesterol targets.

Acetazolamide in Acute Decompensated Heart Failure with Volume Overload.

The ADVOR trial showed that adding intravenous acetazolamide to loop diuretics in patients hospitalized for acute decompensated heart failure significantly improved decongestion success at 3 days compared with placebo. This pragmatic result revived interest in combination diuretic strategies and provided the first large-scale evidence for sequential nephron blockade in acute heart failure.

Randomized Trial of Left Bundle Branch vs Biventricular Pacing for Cardiac Resynchronization Therapy.

This first randomized trial comparing left bundle branch area pacing with biventricular pacing for cardiac resynchronization therapy showed that LBBP achieved comparable or superior echocardiographic response with a simpler implantation procedure. The results positioned LBBP as a viable CRT alternative.

Five-Year Outcomes in Patients With Fully Magnetically Levitated vs Axial-Flow Left Ventricular Assist Devices in the MOMENTUM 3 Randomized Trial.

The 5-year MOMENTUM 3 results confirmed sustained superiority of the HeartMate 3 over the HeartMate II, with significantly better event-free survival and fewer device-related complications. These long-term data solidified the HeartMate 3 as the definitive standard in durable mechanical circulatory support.

Effects of salt substitutes on clinical outcomes

a systematic review and meta-analysis.

This systematic review and meta-analysis confirmed that potassium-enriched salt substitutes lower blood pressure and reduce cardiovascular events and all-cause mortality, reinforcing the SSaSS results and supporting salt substitution as a scalable public health intervention.

Glycemia Reduction in Type 2 Diabetes - Microvascular and Cardiovascular Outcomes.

The GRADE trial compared four glucose-lowering agents added to metformin over 5 years and found that liraglutide and insulin glargine were most durable for glycemic control, while liraglutide had the most favorable cardiovascular profile. The results provided comparative effectiveness data to guide second-line agent selection in type 2 diabetes.

Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction.

The DELIVER trial demonstrated that dapagliflozin significantly reduced the composite of worsening heart failure or cardiovascular death in patients with heart failure and an ejection fraction above 40%, regardless of diabetes status. Together with EMPEROR-Preserved, this confirmed the benefit of SGLT2 inhibitors across the full ejection fraction spectrum.

Harmonization of the American College of Cardiology/American Heart Association and European Society of Cardiology/European Society of Hypertension Blood Pressure/Hypertension Guidelines

Comparisons, Reflections, and Recommendations.

This harmonization document analyzed the similarities and differences between the ACC/AHA and ESC/ESH hypertension guidelines, highlighting converging evidence on treatment initiation thresholds and targets while acknowledging remaining disagreements on classification and risk assessment.

Rivaroxaban in Rheumatic Heart Disease-Associated Atrial Fibrillation.

The INVICTUS trial showed that rivaroxaban was inferior to warfarin for preventing cardiovascular events in patients with rheumatic heart disease-associated atrial fibrillation, with higher rates of stroke, systemic embolism, and death. This landmark negative result confirmed that DOACs cannot replace warfarin in valvular AF due to rheumatic heart disease.

Polypill Strategy in Secondary Cardiovascular Prevention.

The SECURE trial demonstrated that a cardiovascular polypill containing aspirin, ramipril, and atorvastatin reduced major adverse cardiovascular events by 24% compared with separate medications in patients after myocardial infarction. The benefit was attributed to improved adherence, validating the polypill as a practical secondary prevention strategy.

Early Rhythm Control in Patients With Atrial Fibrillation and High Comorbidity Burden.

This EAST-AFNET4 subanalysis showed that early rhythm control reduces cardiovascular events even in AF patients with high comorbidity burden, including those with heart failure, diabetes, and chronic kidney disease. The benefit was not attenuated by comorbidity complexity.

Effect of statin therapy on muscle symptoms

an individual participant data meta-analysis of large-scale, randomised, double-blind trials.

This individual participant data meta-analysis of large-scale, double-blind statin trials in the Lancet showed that statins cause only a small excess of muscle symptoms (about 11 per 1,000 patients over 5 years), with most patient-reported muscle complaints being attributable to the nocebo effect. The findings provide robust reassurance for clinicians managing statin-associated myalgia concerns.

Routine Functional Testing or Standard Care in High-Risk Patients after PCI.

The POST-PCI trial demonstrated that routine functional testing after PCI in high-risk patients did not improve clinical outcomes compared with standard care at 2 years. The results argued against routine surveillance testing as a post-PCI follow-up strategy.

Prevalence of statin intolerance

a meta-analysis.

This meta-analysis estimated that true statin intolerance affects 7-29% of patients depending on the definition used, with nocebo-confirmed intolerance rates being much lower. The data highlighted the gap between perceived and actual statin intolerance and supported rechallenge strategies.

SGLT-2 inhibitors in patients with heart failure

a comprehensive meta-analysis of five randomised controlled trials.

This comprehensive meta-analysis of five major SGLT2 inhibitor trials in heart failure (DAPA-HF, EMPEROR-Reduced, DELIVER, EMPEROR-Preserved, SOLOIST-WHF) confirmed that SGLT2 inhibition reduces heart failure hospitalization and cardiovascular death across the full range of ejection fraction. The analysis provided definitive class-level evidence supporting their use in all heart failure phenotypes.

Fractional Flow Reserve or Intravascular Ultrasonography to Guide PCI.

The FLAVOUR trial demonstrated that FFR-guided PCI was noninferior to IVUS-guided PCI for the composite of death, MI, or revascularization at 24 months in patients with intermediate coronary stenoses. The results validated both physiological and anatomical guidance strategies as acceptable approaches.

Empagliflozin for Heart Failure With Preserved Left Ventricular Ejection Fraction With and Without Diabetes.

This EMPEROR-Preserved subanalysis confirmed that empagliflozin's benefit on heart failure outcomes in HFpEF is consistent regardless of diabetes status, extending the evidence for SGLT2 inhibitors as a universal heart failure therapy beyond glycemic management.

Statin Use for the Primary Prevention of Cardiovascular Disease in Adults

Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

This updated USPSTF evidence review reaffirmed that statin use for primary cardiovascular prevention is associated with reduced cardiovascular events and mortality, supporting continued recommendation for statin therapy in adults at elevated 10-year CVD risk.

Statin Use for the Primary Prevention of Cardiovascular Disease in Adults

US Preventive Services Task Force Recommendation Statement.

The 2022 USPSTF reaffirmation recommended statin use for primary cardiovascular prevention in adults aged 40-75 with at least one CVD risk factor and a 10-year CVD risk of 10% or greater, maintaining the 2016 recommendation with updated evidence review.

Initial Decline (Dip) in Estimated Glomerular Filtration Rate After Initiation of Dapagliflozin in Patients With Heart Failure and Reduced Ejection Fraction

Insights From DAPA-HF.

This DAPA-HF post-hoc analysis showed that the initial eGFR decline ('dip') commonly seen after dapagliflozin initiation is not associated with worse clinical outcomes and is followed by a slower long-term rate of kidney function decline. The finding provided reassurance about the hemodynamic kidney effects of SGLT2 inhibitors.

Long-term efficacy and safety of moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease (RACING)

a randomised, open-label, non-inferiority trial.

This Lancet long-term study demonstrated that moderate-intensity statin combined with ezetimibe was equally effective as high-intensity statin monotherapy for preventing cardiovascular events, with fewer adverse effects. The results supported combination therapy as an alternative to high-dose statins.

Behavioral Counseling Interventions to Promote a Healthy Diet and Physical Activity for Cardiovascular Disease Prevention in Adults Without Cardiovascular Disease Risk Factors

US Preventive Services Task Force Recommendation Statement.

This USPSTF systematic review confirmed that behavioral counseling on diet and physical activity produces modest but consistent cardiovascular risk factor improvements in adults. The evidence supported population-level lifestyle counseling as a component of cardiovascular prevention.

Effects of Early Empagliflozin Initiation on Diuresis and Kidney Function in Patients With Acute Decompensated Heart Failure (EMPAG-HF).

The EMPAG-HF trial demonstrated that early empagliflozin initiation in acute decompensated heart failure significantly increased urinary output without worsening kidney function. The results supported SGLT2 inhibitors as a useful adjunct to loop diuretics for decongestion.

Effects of Empagliflozin on Symptoms, Physical Limitations, and Quality of Life in Patients Hospitalized for Acute Heart Failure

Results From the EMPULSE Trial.

The EMPULSE trial demonstrated that empagliflozin initiated during hospitalization for acute heart failure significantly improved a hierarchical composite of death, heart failure events, and symptoms compared with placebo. The results support in-hospital initiation of SGLT2 inhibitors in acute heart failure.

Effect of Omecamtiv Mecarbil on Exercise Capacity in Chronic Heart Failure With Reduced Ejection Fraction

The METEORIC-HF Randomized Clinical Trial.

The METEORIC-HF trial showed that omecamtiv mecarbil did not improve exercise capacity in patients with HFrEF, despite its positive effects on heart failure events in GALACTIC-HF. The disconnect between clinical outcomes and functional capacity measures remains unexplained.

Effect of MRI-Guided Fibrosis Ablation vs Conventional Catheter Ablation on Atrial Arrhythmia Recurrence in Patients With Persistent Atrial Fibrillation

The DECAAF II Randomized Clinical Trial.

The DECAAF II trial showed that MRI-guided fibrosis ablation did not improve freedom from atrial arrhythmia compared with conventional catheter ablation in patients with persistent AF. The negative result suggested that current MRI-based fibrosis mapping does not reliably guide ablation targets.

Does Timing of Ventricular Tachycardia Ablation Affect Prognosis in Patients With an Implantable Cardioverter Defibrillator? Results From the Multicenter Randomized PARTITA Trial.

The PARTITA trial demonstrated that early VT ablation after the first appropriate ICD shock reduced the composite of heart failure hospitalization or death compared with delayed ablation after subsequent shocks. The results supported a proactive ablation strategy rather than waiting for recurrent VT.

Randomized Ablation-Based Rhythm-Control Versus Rate-Control Trial in Patients With Heart Failure and Atrial Fibrillation

Results from the RAFT-AF trial.

The RAFT-AF trial showed that ablation-based rhythm control improved left ventricular function and NT-proBNP levels compared with rate control in patients with heart failure and AF, though it did not significantly reduce the composite of mortality and heart failure events. The echocardiographic benefit supported ablation for AF in heart failure.

Effects of Long-term Metformin and Lifestyle Interventions on Cardiovascular Events in the Diabetes Prevention Program and Its Outcome Study.

After 21 years of follow-up in the Diabetes Prevention Program, neither lifestyle intervention nor metformin reduced the incidence of cardiovascular events compared with placebo, despite their proven diabetes prevention effects. The result indicated that metabolic prevention alone does not translate to cardiovascular event reduction.

Bariatric surgery and cardiovascular disease

a systematic review and meta-analysis.

This systematic review and meta-analysis showed that bariatric surgery is associated with significant reductions in cardiovascular events and cardiovascular mortality compared with nonsurgical management of obesity. The quantified cardiovascular benefit supports consideration of bariatric surgery as a cardiovascular prevention strategy.

Treatment for Mild Chronic Hypertension during Pregnancy.

The CHAP trial demonstrated that treatment of mild chronic hypertension during pregnancy (targeting blood pressure <140/90 mmHg) significantly reduced the risk of preeclampsia and preterm birth with no adverse fetal effects. This landmark result reversed the prevailing watchful-waiting approach and established active treatment as beneficial in pregnancy-associated hypertension.

Effect of Alirocumab Added to High-Intensity Statin Therapy on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction

The PACMAN-AMI Randomized Clinical Trial.

The PACMAN-AMI trial demonstrated that adding alirocumab to high-intensity statin therapy after acute MI produced greater reductions in coronary plaque volume and improved plaque composition on multimodality intravascular imaging compared with statin alone. The results provided direct evidence that early PCSK9 inhibition favorably modifies vulnerable plaques.

2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure

Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

Executive summary of the 2022 AHA/ACC/HFSA heart failure guideline, providing key recommendations, decision pathways, and the four-pillar treatment algorithm for HFrEF including SGLT2 inhibitors, ARNI, beta-blockers, and MRAs.

2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure

A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

The 2022 AHA/ACC/HFSA heart failure guideline published in JACC replaced the 2013 guidelines and integrated contemporary evidence on SGLT2 inhibitors and ARNI into structured treatment algorithms for heart failure across the ejection fraction spectrum.

2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure

A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

The 2022 AHA/ACC/HFSA heart failure guideline was the first comprehensive update since 2013, integrating SGLT2 inhibitors, sacubitril-valsartan, and vericiguat into guideline-directed medical therapy. The document codified the four-pillar approach to HFrEF and provided new recommendations for HFpEF management based on emerging evidence.

Aspirin Use to Prevent Cardiovascular Disease

US Preventive Services Task Force Recommendation Statement.

The 2022 USPSTF recommendation statement downgraded the role of aspirin in primary cardiovascular prevention, advising against initiation in adults 60 years or older and recommending individualized decision-making in those aged 40–59 with elevated CVD risk. This reflected accumulating evidence from ASPREE, ARRIVE, and ASCEND showing unfavorable bleeding-to-benefit ratios.

Safety of the oral factor XIa inhibitor asundexian compared with apixaban in patients with atrial fibrillation (PACIFIC-AF)

a multicentre, randomised, double-blind, double-dummy, dose-finding phase 2 study.

The PACIFIC-AF phase 2 trial showed that asundexian, an oral factor XIa inhibitor, had significantly less bleeding than apixaban in AF patients while maintaining preliminary signals of anticoagulant efficacy. This early positive result set the stage for the subsequent (failed) OCEANIC-AF phase 3 trial.

Reduction of dietary sodium to less than 100 mmol in heart failure (SODIUM-HF)

an international, open-label, randomised, controlled trial.

The SODIUM-HF trial showed that strict dietary sodium restriction (<100 mmol/day) in heart failure patients did not significantly reduce the composite of cardiovascular hospitalization, emergency department visit, or death compared with usual care. The neutral result questioned the clinical benefit of intensive sodium restriction.

Systematic, early rhythm control strategy for atrial fibrillation in patients with or without symptoms

the EAST-AFNET 4 trial.

This EAST-AFNET 4 analysis showed that early rhythm control improves outcomes in AF patients regardless of symptom status, expanding the indication beyond symptomatic patients. The finding challenged the guideline restriction of rhythm control to symptomatic AF.

Comparative effects of guided vs. potent P2Y12 inhibitor therapy in acute coronary syndrome

a network meta-analysis of 61 898 patients from 15 randomized trials.

This network meta-analysis of nearly 62,000 ACS patients compared guided de-escalation with potent P2Y12 inhibitor therapy, finding that guided approaches reduce bleeding without increasing ischemic events. The comprehensive analysis supported precision antiplatelet strategies as a superior alternative.

Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease

the FIDELITY pooled analysis.

The FIDELITY pooled analysis combined FIDELIO-DKD and FIGARO-DKD data to demonstrate consistent cardiovascular and kidney benefits of finerenone across the full spectrum of CKD severity in patients with type 2 diabetes. This definitive analysis established finerenone's position in the cardiorenal protection armamentarium.

Finerenone Reduces Risk of Incident Heart Failure in Patients With Chronic Kidney Disease and Type 2 Diabetes

Analyses From the FIGARO-DKD Trial.

This FIDELITY pooled analysis demonstrated that finerenone reduces the risk of new-onset heart failure in patients with CKD and type 2 diabetes, adding heart failure prevention to the established renal and cardiovascular benefits of nonsteroidal mineralocorticoid receptor antagonism.

Screening for Atrial Fibrillation

US Preventive Services Task Force Recommendation Statement.

The 2022 USPSTF reaffirmed the insufficient evidence ('I' statement) for ECG screening for atrial fibrillation in asymptomatic older adults, despite advancing wearable technology, due to the lack of randomized trials demonstrating that screening-detected AF treatment improves outcomes.

Direct Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation

Patient-Level Network Meta-Analyses of Randomized Clinical Trials With Interaction Testing by Age and Sex.

This patient-level network meta-analysis of all four DOACs versus warfarin in atrial fibrillation confirmed the class-wide superiority of DOACs for stroke prevention with less intracranial hemorrhage. The analysis also provided the first robust head-to-head indirect comparisons between individual DOACs.

2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization

Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

The 2021 ACC/AHA/SCAI coronary revascularization guideline executive summary integrated evidence from ISCHEMIA, EXCEL, NOBLE, and contemporary trials to update recommendations for PCI versus CABG decision-making. The document emphasized heart team consultation, functional ischemia testing, and patient-centered shared decision-making for complex coronary disease.

Fractional Flow Reserve-Guided PCI as Compared with Coronary Bypass Surgery.

The FAME 3 trial showed that FFR-guided PCI was not noninferior to CABG for the composite of death, MI, stroke, or repeat revascularization at 1 year in patients with three-vessel coronary artery disease. The result reinforced CABG as the preferred strategy for extensive multivessel disease.

Chlorthalidone for Hypertension in Advanced Chronic Kidney Disease.

The CLICK trial demonstrated that chlorthalidone effectively lowered blood pressure in patients with advanced CKD (eGFR 15-30 mL/min), a population traditionally thought unresponsive to thiazide diuretics. This evidence-changing result supported the use of thiazide-like diuretics even in severe kidney disease.

Angiography after Out-of-Hospital Cardiac Arrest without ST-Segment Elevation.

The TOMAHAWK trial confirmed that immediate coronary angiography did not improve 30-day survival compared with a delayed approach in patients resuscitated from out-of-hospital cardiac arrest without ST-segment elevation. Together with COACT, this definitively argued against routine emergent catheterization in this setting.

Effect of Long-Term Marine ɷ-3 Fatty Acids Supplementation on the Risk of Atrial Fibrillation in Randomized Controlled Trials of Cardiovascular Outcomes

A Systematic Review and Meta-Analysis.

This meta-analysis of randomized controlled trials confirmed that long-term marine omega-3 fatty acid supplementation is associated with a significantly increased risk of atrial fibrillation. The definitive safety signal raised concerns about the cardiovascular use of fish oil supplements.

Percutaneous coronary intervention with drug-eluting stents versus coronary artery bypass grafting in left main coronary artery disease

an individual patient data meta-analysis.

The PRECOMBAT 10-year follow-up showed no significant difference in the composite of death, MI, stroke, or revascularization between PCI with DES and CABG for left main coronary disease, though individual event rates favored CABG numerically. The long-term Korean data added to the revascularization debate.

Angiographic quantitative flow ratio-guided coronary intervention (FAVOR III China)

a multicentre, randomised, sham-controlled trial.

The FAVOR III China trial demonstrated that angiographic quantitative flow ratio (QFR)-guided PCI significantly improved 1-year outcomes compared with angiography-guided PCI. The wire-free virtual physiological assessment offered a practical alternative to pressure wire-based FFR measurement.

Cardiovascular Events with Finerenone in Kidney Disease and Type 2 Diabetes.

The FIGARO-DKD trial demonstrated that finerenone reduced cardiovascular events in patients with type 2 diabetes and a broader range of CKD severity than FIDELIO, including those with earlier-stage kidney disease and less severely elevated albuminuria. Together with FIDELIO, the FIDELITY program established finerenone's cardiorenal benefit across the full CKD spectrum in diabetes.

AV junction ablation and cardiac resynchronization for patients with permanent atrial fibrillation and narrow QRS

the APAF-CRT mortality trial.

The APAF-CRT mortality analysis confirmed that AV junction ablation combined with cardiac resynchronization therapy significantly reduced all-cause mortality in patients with permanent atrial fibrillation, narrow QRS, and heart failure. The result established this strategy as a life-saving intervention in drug-refractory AF with HF.

Posterior left pericardiotomy for the prevention of atrial fibrillation after cardiac surgery

an adaptive, single-centre, single-blind, randomised, controlled trial.

The PALACS trial demonstrated that posterior left pericardiotomy, a simple 30-second surgical addition during cardiac surgery, significantly reduced the incidence of postoperative atrial fibrillation. The low-cost, low-risk intervention offered an elegant preventive strategy.

Edoxaban versus Vitamin K Antagonist for Atrial Fibrillation after TAVR.

The ENVISAGE-TAVI AF trial showed that edoxaban was noninferior to vitamin K antagonists for the composite of net adverse clinical events in patients with AF after TAVR, but was associated with more gastrointestinal bleeding. The results informed DOAC use in the growing post-TAVR AF population.

Blood pressure lowering and risk of new-onset type 2 diabetes

an individual participant data meta-analysis.

This BPLTTC meta-analysis revealed that pharmacological blood pressure lowering reduces the risk of new-onset type 2 diabetes, with an estimated 11% relative risk reduction per 5 mmHg systolic blood pressure decrease. The unexpected metabolic benefit adds a new dimension to the argument for aggressive blood pressure management.

Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4)

a randomised, open-label, parallel-group, multicentre, phase 3 trial.

The SURPASS-4 trial showed that tirzepatide was superior to insulin glargine for HbA1c reduction and weight loss in patients with type 2 diabetes and increased cardiovascular risk, while demonstrating cardiovascular safety in this high-risk population.

Angiotensin Receptor-Neprilysin Inhibition in Acute Myocardial Infarction.

The PARADISE-MI trial found that sacubitril-valsartan did not significantly reduce the composite of cardiovascular death or heart failure events compared with ramipril in patients with acute MI and reduced left ventricular function. The result indicated that ARNI therapy does not provide additional benefit over ACE inhibition in the post-MI setting.

Influenza Vaccination After Myocardial Infarction

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial.

The IAMI trial showed that influenza vaccination administered within 72 hours of myocardial infarction or high-risk coronary intervention reduced the composite of all-cause death, MI, or stent thrombosis at 12 months. This is the first large, placebo-controlled trial demonstrating the cardiovascular protective effect of influenza vaccination after acute coronary events.

Dual Antiplatelet Therapy after PCI in Patients at High Bleeding Risk.

The MASTER DAPT trial showed that abbreviated 1-month dual antiplatelet therapy followed by single antiplatelet therapy was noninferior to standard DAPT for net adverse clinical events in high-bleeding-risk patients after drug-eluting stent implantation. The results support a shortened DAPT duration in this vulnerable population.

Clinical outcomes in systematic screening for atrial fibrillation (STROKESTOP)

a multicentre, parallel group, unmasked, randomised controlled trial.

The STROKESTOP trial demonstrated that systematic screening for atrial fibrillation in 75-76-year-olds using intermittent ECG recordings, followed by anticoagulation when AF was detected, reduced the composite of ischemic stroke, systemic embolism, bleeding, and death compared with no screening. This is the first randomized trial showing clinical benefit from population-level AF screening.

Effect of Empagliflozin on Worsening Heart Failure Events in Patients With Heart Failure and Preserved Ejection Fraction

EMPEROR-Preserved Trial.

This EMPEROR-Preserved analysis detailed that empagliflozin reduced worsening heart failure events across the ejection fraction spectrum in HFpEF, with consistent benefit regardless of baseline LVEF, diabetes status, or renal function.

Empagliflozin in Heart Failure with a Preserved Ejection Fraction.

The EMPEROR-Preserved trial was the first to demonstrate that an SGLT2 inhibitor (empagliflozin) reduces heart failure hospitalization in patients with HFpEF. This landmark result extended the benefit of SGLT2 inhibition across the full ejection fraction spectrum, addressing an area with previously no proven pharmacological therapy.

Empagliflozin and Major Renal Outcomes in Heart Failure.

This EMPEROR-Reduced renal analysis showed that empagliflozin slowed the decline in eGFR and reduced the risk of serious kidney outcomes in patients with heart failure, demonstrating renoprotective effects of SGLT2 inhibition in the heart failure population.

Unguided de-escalation from ticagrelor to clopidogrel in stabilised patients with acute myocardial infarction undergoing percutaneous coronary intervention (TALOS-AMI)

an investigator-initiated, open-label, multicentre, non-inferiority, randomised trial.

The TALOS-AMI trial demonstrated that unguided de-escalation from ticagrelor to clopidogrel one month after MI reduced bleeding without increasing ischemic events. The pragmatic approach, requiring no platelet function testing, offered a simpler de-escalation strategy than guided protocols.

Trial of Intensive Blood-Pressure Control in Older Patients with Hypertension.

The STEP trial demonstrated that intensive blood pressure control (target 110–130 mmHg) significantly reduced cardiovascular events compared with standard treatment (130–150 mmHg) in Chinese patients aged 60–80 with hypertension. The results confirmed the benefits of intensive blood pressure targets in older adults, extending the findings of SPRINT to an Asian population.

Initial treatment with a single pill containing quadruple combination of quarter doses of blood pressure medicines versus standard dose monotherapy in patients with hypertension (QUARTET)

a phase 3, randomised, double-blind, active-controlled trial.

The QUARTET trial showed that initial treatment with a quarter-dose quadruple combination blood pressure pill achieved superior blood pressure control compared with standard care monotherapy at 12 weeks. The results support ultra-low-dose combination therapy as an effective strategy to overcome treatment inertia in hypertension.

Effect of Salt Substitution on Cardiovascular Events and Death.

The SSaSS trial showed that replacing regular salt with a potassium-enriched salt substitute in 20,995 participants significantly reduced stroke, cardiovascular events, and all-cause mortality without increasing hyperkalemia. This is the largest dietary intervention trial in cardiovascular prevention and demonstrates a scalable public health strategy.

Haemodynamic-guided management of heart failure (GUIDE-HF)

a randomised controlled trial.

The GUIDE-HF trial of hemodynamic-guided heart failure management with implantable PA pressure sensors showed no significant overall benefit, though a pre-COVID subanalysis suggested reduced heart failure events. The results highlighted the confounding impact of the pandemic on heart failure trials.

Cardiovascular and Renal Outcomes with Efpeglenatide in Type 2 Diabetes.

The AMPLITUDE-O trial demonstrated that efpeglenatide, an exendin-based GLP-1 receptor agonist, reduced cardiovascular events and kidney outcomes in patients with type 2 diabetes at high cardiovascular risk. This was the sixth positive GLP-1 RA cardiovascular outcomes trial, extending the class benefit to a structurally distinct agent.

2021 ACC Expert Consensus Decision Pathway on the Management of ASCVD Risk Reduction in Patients With Persistent Hypertriglyceridemia

A Report of the American College of Cardiology Solution Set Oversight Committee.

The 2021 ACC Expert Consensus addressed ASCVD risk reduction in patients with persistent hypertriglyceridemia, providing decision algorithms integrating icosapent ethyl, fibrates, and lifestyle modification based on the REDUCE-IT and STRENGTH evidence.

Lowering cholesterol, blood pressure, or both to prevent cardiovascular events

results of 8.7 years of follow-up of Heart Outcomes Evaluation Prevention (HOPE)-3 study participants.

The HOPE-3 extended 8.7-year follow-up showed that the cardiovascular benefits of rosuvastatin observed during the active treatment period persisted after trial completion, suggesting a legacy effect of intermediate-risk lipid lowering on long-term cardiovascular protection.

Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3)

a randomised, open-label, parallel-group, phase 3 trial.

The SURPASS-3 trial demonstrated that tirzepatide was superior to insulin degludec for glycemic control and weight loss when added to metformin with or without an SGLT2 inhibitor in type 2 diabetes. The results positioned tirzepatide as a potent alternative to basal insulin.

Milrinone as Compared with Dobutamine in the Treatment of Cardiogenic Shock.

The DOREMI trial found no significant difference between milrinone and dobutamine for the primary outcome in patients with cardiogenic shock. As the first large head-to-head comparison of inotropes in shock, it established that neither agent is clearly superior.

Multivessel PCI Guided by FFR or Angiography for Myocardial Infarction.

The FLOWER-MI trial showed that FFR-guided complete revascularization of nonculprit lesions did not reduce the composite of death, MI, or urgent revascularization compared with angiography-guided PCI in patients with STEMI and multivessel disease. The surprising negative result questioned the added value of FFR guidance in the acute MI setting.

Efficacy and safety of low-dose colchicine in patients with coronary disease

a systematic review and meta-analysis of randomized trials.

This meta-analysis of colchicine trials in coronary disease confirmed that low-dose colchicine reduces cardiovascular events with an acceptable safety profile, integrating COLCOT, LoDoCo2, and COPS data. The pooled evidence supported colchicine as a cost-effective anti-inflammatory strategy.

Physical Rehabilitation for Older Patients Hospitalized for Heart Failure.

The REHAB-HF trial showed that a tailored physical rehabilitation intervention improved physical function and frailty in older patients hospitalized for acute heart failure, though it did not significantly reduce rehospitalization or death. The functional benefit supports rehabilitation in elderly heart failure patients.

Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1)

a double-blind, randomised, phase 3 trial.

The SURPASS-1 trial demonstrated that tirzepatide, a novel dual GIP/GLP-1 receptor agonist, produced superior HbA1c reduction and weight loss compared with placebo as monotherapy in type 2 diabetes. These first phase 3 results foreshadowed the transformative potential of dual incretin agonism.

Aspirin versus clopidogrel for chronic maintenance monotherapy after percutaneous coronary intervention (HOST-EXAM)

an investigator-initiated, prospective, randomised, open-label, multicentre trial.

The HOST-EXAM trial showed that clopidogrel was superior to aspirin for chronic maintenance antiplatelet monotherapy after PCI, reducing the composite of cardiovascular death, MI, stroke, readmission for ACS, or stent thrombosis at 24 months. The result challenged aspirin as the default long-term antiplatelet agent after coronary stenting.

Ultrasound renal denervation for hypertension resistant to a triple medication pill (RADIANCE-HTN TRIO)

a randomised, multicentre, single-blind, sham-controlled trial.

The RADIANCE-HTN TRIO trial demonstrated that ultrasound-based renal denervation significantly reduced daytime ambulatory systolic blood pressure compared with a sham procedure in patients with resistant hypertension on a standardized triple combination pill. This was the first positive renal denervation trial in true resistant hypertension.

Left Atrial Appendage Occlusion during Cardiac Surgery to Prevent Stroke.

The LAAOS III trial demonstrated that surgical left atrial appendage occlusion performed during cardiac surgery significantly reduced the risk of ischemic stroke or systemic embolism in patients with atrial fibrillation. This simple addition to planned cardiac surgery provides lasting stroke protection as an adjunct to anticoagulation.

Assessment of Catheter Ablation or Antiarrhythmic Drugs for First-line Therapy of Atrial Fibrillation

A Meta-analysis of Randomized Clinical Trials.

This JAMA Cardiology meta-analysis of randomized trials confirmed that catheter ablation as first-line therapy for atrial fibrillation is superior to antiarrhythmic drugs for maintaining sinus rhythm, with potential benefits on cardiovascular outcomes. The pooled data supported the shift toward earlier ablation.

Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease.

The ADAPTABLE trial, the first large pragmatic trial comparing aspirin doses in cardiovascular disease, found no significant difference between 81 mg and 325 mg daily for preventing cardiovascular events or causing major bleeding. The results support low-dose aspirin as the standard for secondary prevention.

Final Report of a Trial of Intensive versus Standard Blood-Pressure Control.

The final SPRINT report, including post-trial follow-up, confirmed the durable benefit of intensive systolic blood pressure control (target <120 mmHg) versus standard treatment (target <140 mmHg) in reducing cardiovascular events and mortality. The sustained benefit after treatment cessation strengthened the case for aggressive blood pressure targets.

Do β-Blockers Cause Depression?

Systematic Review and Meta-Analysis of Psychiatric Adverse Events During β-Blocker Therapy.

This systematic review and meta-analysis found no significant association between beta-blocker therapy and increased risk of depression, debunking a widely held clinical belief. The evidence addressed one of the most common reasons patients and clinicians avoid beta-blockers.

Pharmacological blood pressure lowering for primary and secondary prevention of cardiovascular disease across different levels of blood pressure

an individual participant-level data meta-analysis.

This individual-participant-data meta-analysis from the BPLTTC demonstrated that pharmacological blood pressure lowering reduces cardiovascular events across all baseline blood pressure levels, including in individuals with normal or high-normal pressure. The findings support a strategy of treating based on absolute cardiovascular risk rather than blood pressure thresholds alone.

Guided versus standard antiplatelet therapy in patients undergoing percutaneous coronary intervention

a systematic review and meta-analysis.

This Lancet meta-analysis showed that guided antiplatelet therapy selection (pharmacogenomic or pharmacodynamic testing) after PCI reduces ischemic and bleeding events compared with standard unguided therapy. The results supported precision medicine approaches to antiplatelet management.

2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation.

The 2020 ESC Guidelines for non-ST-elevation acute coronary syndromes updated risk stratification, timing of invasive management, and antithrombotic strategies incorporating evidence from ISCHEMIA, TWILIGHT, and contemporary trials. The guideline refined the balance between ischemic protection and bleeding risk in ACS patients.

Effects of dapagliflozin on mortality in patients with chronic kidney disease

a pre-specified analysis from the DAPA-CKD randomized controlled trial.

This pre-specified DAPA-CKD mortality analysis confirmed that dapagliflozin significantly reduces all-cause mortality in patients with chronic kidney disease, independent of diabetes status. The survival benefit strengthened the case for universal SGLT2 inhibitor use in CKD.

Effect of Marine Omega-3 Fatty Acid and Vitamin D Supplementation on Incident Atrial Fibrillation

A Randomized Clinical Trial.

The VITAL-AF trial unexpectedly showed that marine omega-3 fatty acid supplementation was associated with increased risk of atrial fibrillation, while vitamin D had no effect. The pro-arrhythmic signal contradicted the assumed cardiovascular benefit of fish oil supplements.

3-Year Outcomes of Transcatheter Mitral Valve Repair in Patients With Heart Failure.

The COAPT 3-year results confirmed sustained benefit of transcatheter mitral valve repair with MitraClip in heart failure with severe secondary mitral regurgitation, with persistent reductions in hospitalization and mortality beyond the 2-year primary endpoint.

2021 Update to the 2017 ACC Expert Consensus Decision Pathway for Optimization of Heart Failure Treatment

Answers to 10 Pivotal Issues About Heart Failure With Reduced Ejection Fraction: A Report of the American College of Cardiology Solution Set Oversight Committee.

The 2021 ACC Expert Consensus update addressed 10 pivotal questions on heart failure treatment optimization, integrating evidence for SGLT2 inhibitors across the ejection fraction spectrum, vericiguat in recently decompensated HFrEF, and practical implementation of quadruple therapy.

Effect of High-Intensity Interval Training, Moderate Continuous Training, or Guideline-Based Physical Activity Advice on Peak Oxygen Consumption in Patients With Heart Failure With Preserved Ejection Fraction

A Randomized Clinical Trial.

The SMARTEX-HF trial showed that high-intensity interval training was not superior to moderate continuous training for improving peak VO2 in patients with HFrEF. The result supported moderate exercise as safe and effective, without an incremental benefit from more intense training in heart failure.

2020 ACC Expert Consensus Decision Pathway for Anticoagulant and Antiplatelet Therapy in Patients With Atrial Fibrillation or Venous Thromboembolism Undergoing Percutaneous Coronary Intervention or With Atherosclerotic Cardiovascular Disease

A Report of the American College of Cardiology Solution Set Oversight Committee.

The 2020 ACC Expert Consensus provided a comprehensive decision pathway for managing antithrombotic therapy in patients with atrial fibrillation or venous thromboembolism who require antiplatelet agents, with practical algorithms for diverse clinical scenarios.

Finerenone and Cardiovascular Outcomes in Patients With Chronic Kidney Disease and Type 2 Diabetes.

The FIDELIO-DKD trial demonstrated that finerenone, a nonsteroidal mineralocorticoid receptor antagonist, significantly reduced both kidney failure progression and cardiovascular events in patients with chronic kidney disease and type 2 diabetes. This established finerenone as a new therapeutic pillar in cardiorenal protection alongside SGLT2 inhibitors and GLP-1 receptor agonists.

Association of SGLT2 Inhibitors With Cardiovascular and Kidney Outcomes in Patients With Type 2 Diabetes

A Meta-analysis.

This JAMA Cardiology meta-analysis updated the evidence on SGLT2 inhibitor cardiovascular and kidney outcomes in type 2 diabetes, confirming class-consistent reductions in heart failure hospitalization, cardiovascular death, and kidney disease progression across all available agents.

Inhaled Treprostinil in Pulmonary Hypertension Due to Interstitial Lung Disease.

The INCREASE trial demonstrated that inhaled treprostinil improved exercise capacity in patients with pulmonary hypertension associated with interstitial lung disease. This was the first therapy proven effective for this specific, previously untreatable form of pulmonary hypertension.

Cryoablation or Drug Therapy for Initial Treatment of Atrial Fibrillation.

The STOP AF First trial confirmed that cryoablation was superior to antiarrhythmic drug therapy as initial treatment for paroxysmal atrial fibrillation, with significantly fewer patients experiencing treatment failure at 1 year. Together with EARLY-AF, the trial established the evidence base for first-line ablation in AF.

Cryoballoon Ablation as Initial Therapy for Atrial Fibrillation.

The EARLY-AF trial showed that cryoballoon ablation as initial therapy for symptomatic paroxysmal atrial fibrillation was superior to antiarrhythmic drug therapy in maintaining sinus rhythm at 1 year. This landmark result challenged the guideline recommendation of a drug-first approach and supported ablation as a first-line strategy.

Randomized Trial of Empagliflozin in Nondiabetic Patients With Heart Failure and Reduced Ejection Fraction.

This EMPEROR-Reduced subanalysis in nondiabetic patients confirmed that empagliflozin reduces cardiovascular death and heart failure hospitalization regardless of diabetes status. The finding was pivotal for regulatory approval of SGLT2 inhibitors in heart failure independent of glycemic indication.

Short dual antiplatelet therapy followed by P2Y12 inhibitor monotherapy vs. prolonged dual antiplatelet therapy after percutaneous coronary intervention with second-generation drug-eluting stents

a systematic review and meta-analysis of randomized clinical trials.

This meta-analysis confirmed that short DAPT followed by P2Y12 inhibitor monotherapy significantly reduces bleeding compared with prolonged DAPT after PCI with second-generation DES, without increasing ischemic events. The pooled evidence consolidated the de-escalation paradigm.

Polypill with or without Aspirin in Persons without Cardiovascular Disease.

The PolyPill-TIPS-3 trial showed that a polypill containing a statin and two blood-pressure-lowering drugs, with or without aspirin, reduced the incidence of cardiovascular disease in intermediate-risk individuals without established CVD. The study validated the polypill strategy as a practical approach to primary cardiovascular prevention at the population level.

Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure.

The SOLOIST-WHF trial demonstrated that sotagliflozin initiated before or shortly after hospital discharge for worsening heart failure significantly reduced cardiovascular death and heart failure events in patients with diabetes. The study provided the first evidence for starting SGLT inhibitor therapy during an acute heart failure hospitalization.

Sotagliflozin in Patients with Diabetes and Chronic Kidney Disease.

The SCORED trial showed that sotagliflozin, a dual SGLT1/SGLT2 inhibitor, reduced cardiovascular death, heart failure hospitalization, and urgent heart failure visits in patients with type 2 diabetes and chronic kidney disease. The results established dual SGLT inhibition as an effective cardiorenal strategy.

Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure.

The GALACTIC-HF trial demonstrated that omecamtiv mecarbil, a selective cardiac myosin activator, modestly reduced the composite of heart failure events or cardiovascular death in patients with HFrEF. The trial validated a novel mechanism targeting cardiac contractility without increasing intracellular calcium or myocardial oxygen demand.

Effect of Digoxin vs Bisoprolol for Heart Rate Control in Atrial Fibrillation on Patient-Reported Quality of Life

The RATE-AF Randomized Clinical Trial.

The RATE-AF trial showed that digoxin was noninferior to bisoprolol for quality-of-life outcomes in patients with permanent AF and symptoms of heart failure, with fewer treatment-related adverse events. The pragmatic result supported digoxin as a reasonable first-line rate control agent in this population.

Ferric carboxymaltose for iron deficiency at discharge after acute heart failure

a multicentre, double-blind, randomised, controlled trial.

The AFFIRM-AHF trial showed that intravenous ferric carboxymaltose in patients with iron deficiency discharged after acute heart failure reduced the composite of heart failure rehospitalization and cardiovascular death versus placebo. This landmark result established IV iron as a guideline-recommended therapy for iron-deficient heart failure patients.

Evinacumab in Patients with Refractory Hypercholesterolemia.

This NEJM trial demonstrated that evinacumab significantly reduced LDL cholesterol in patients with refractory hypercholesterolemia who had not reached LDL goals despite maximum tolerated lipid-lowering therapy. The results extended the utility of ANGPTL3 inhibition beyond homozygous FH to a broader treatment-resistant population.

Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk

The STRENGTH Randomized Clinical Trial.

The STRENGTH trial showed that high-dose omega-3 fatty acids (EPA plus DHA) did not reduce major cardiovascular events compared with corn oil in statin-treated patients at high cardiovascular risk. The contrasting result with REDUCE-IT (EPA only) suggested that DHA may attenuate EPA's cardiovascular benefit or that the mineral oil placebo in REDUCE-IT may have influenced outcomes.

Rivaroxaban in Patients with Atrial Fibrillation and a Bioprosthetic Mitral Valve.

The RIVER trial demonstrated that rivaroxaban was noninferior to warfarin for the composite of stroke, TIA, systemic embolism, valve thrombosis, or death in patients with atrial fibrillation and a bioprosthetic mitral valve. The result expanded the evidence for DOAC use in patients with bioprosthetic heart valves.

N-of-1 Trial of a Statin, Placebo, or No Treatment to Assess Side Effects.

The StatinWISE N-of-1 trial demonstrated that muscle symptoms attributed to statins were largely not reproducible under blinded conditions, with similar symptom scores during statin and placebo periods. This provided rigorous evidence that most statin-associated side effects are attributable to the nocebo effect rather than the drug itself.

Efficacy and safety of lowering LDL cholesterol in older patients

a systematic review and meta-analysis of randomised controlled trials.

This Lancet meta-analysis of randomized controlled trials confirmed that LDL cholesterol-lowering therapy reduces cardiovascular events in older patients to a similar extent as in younger patients. The analysis definitively countered the notion that lipid lowering is ineffective or unsafe in elderly populations.

Lipoprotein(a) lowering by alirocumab reduces the total burden of cardiovascular events independent of low-density lipoprotein cholesterol lowering

ODYSSEY OUTCOMES trial.

This ODYSSEY OUTCOMES analysis showed that alirocumab-mediated Lp(a) reduction independently contributed to lowering the total burden of cardiovascular events, beyond LDL cholesterol effects. The finding strengthened the evidence for Lp(a) as an actionable therapeutic target.

Colchicine in Patients With Acute Coronary Syndrome

The Australian COPS Randomized Clinical Trial.

The Australian COPS trial showed that colchicine initiated during ACS hospitalization did not reduce cardiovascular events and was associated with a signal toward increased noncardiovascular mortality. The unexpected negative result contrasted with COLCOT and contributed to ongoing uncertainty about colchicine's role in ACS.

Screening for High Blood Pressure in Children and Adolescents

US Preventive Services Task Force Recommendation Statement.

The 2020 USPSTF recommendation on blood pressure screening in children and adolescents addressed the evidence for routine screening and identification of primary and secondary hypertension in the pediatric population.

Complete revascularization reduces cardiovascular death in patients with ST-segment elevation myocardial infarction and multivessel disease

systematic review and meta-analysis of randomized clinical trials.

This meta-analysis demonstrated that complete revascularization of nonculprit lesions in patients with STEMI and multivessel disease significantly reduces cardiovascular death, providing the strongest evidence yet for a mortality benefit from the complete revascularization strategy.

Redevelopment and validation of the SYNTAX score II to individualise decision making between percutaneous and surgical revascularisation in patients with complex coronary artery disease

secondary analysis of the multicentre randomised controlled SYNTAXES trial with external cohort validation.

The redeveloped SYNTAX Score II integrates clinical and anatomical variables to provide individualized predictions of outcomes after PCI versus CABG, enabling personalized revascularization decisions based on predicted benefit rather than average trial results.

Low-Dose Edoxaban in Very Elderly Patients with Atrial Fibrillation.

The ELDERCARE-AF trial showed that low-dose edoxaban (15 mg daily) significantly reduced stroke and systemic embolism compared with placebo in very elderly (≥80 years) Japanese patients with atrial fibrillation who were deemed inappropriate for standard-dose anticoagulation. The findings addressed a critical evidence gap in the frailest AF population.

Dual Antiplatelet Therapy After Percutaneous Coronary Intervention and Drug-Eluting Stents

A Systematic Review and Network Meta-Analysis.

This comprehensive network meta-analysis evaluated the optimal duration and intensity of DAPT after PCI with drug-eluting stents, comparing short-term, standard, and extended regimens. The analysis provided quantitative guidance for personalizing DAPT duration based on individual risk profiles.

Prasugrel-based de-escalation of dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (HOST-REDUCE-POLYTECH-ACS)

an open-label, multicentre, non-inferiority randomised trial.

This Lancet trial of prasugrel dose de-escalation (from 10 mg to 5 mg) after the acute phase of ACS demonstrated that dose reduction provides a less bleeding-prone alternative to switching agents. The approach offered a practical de-escalation strategy within a single P2Y12 inhibitor.

Dapagliflozin in Patients with Chronic Kidney Disease.

The DAPA-CKD trial demonstrated that dapagliflozin significantly reduced the composite of sustained decline in eGFR, end-stage kidney disease, or death from renal or cardiovascular causes in patients with CKD, regardless of diabetes status. The trial was stopped early for efficacy and expanded the role of SGLT2 inhibitors to all chronic kidney disease.

Cardiovascular Outcomes with Ertugliflozin in Type 2 Diabetes.

The VERTIS CV trial confirmed the cardiovascular safety (noninferiority) of ertugliflozin in patients with type 2 diabetes and established atherosclerotic disease but did not demonstrate superiority for MACE reduction. The result differentiated ertugliflozin from empagliflozin and canagliflozin within the SGLT2 inhibitor class.

Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure.

The EMPEROR-Reduced trial showed that empagliflozin significantly reduced the composite of cardiovascular death or heart failure hospitalization in patients with HFrEF, regardless of diabetes status. Together with DAPA-HF, this confirmed the class effect of SGLT2 inhibitors in heart failure and supported their addition to guideline-directed therapy.

Early Rhythm-Control Therapy in Patients with Atrial Fibrillation.

The EAST-AFNET 4 trial demonstrated that early, systematic rhythm-control therapy within one year of atrial fibrillation diagnosis reduced cardiovascular death, stroke, and hospitalization for heart failure compared with usual care. This paradigm-shifting result reversed decades of rate-control-first thinking and established early rhythm control as the preferred strategy.

Evolocumab in Pediatric Heterozygous Familial Hypercholesterolemia.

The HAUSER-RCT trial demonstrated that evolocumab safely and effectively lowered LDL cholesterol in children and adolescents (10-17 years) with heterozygous familial hypercholesterolemia, providing the first randomized evidence for PCSK9 inhibitor use in the pediatric FH population.

Natural History of Asymptomatic Severe Aortic Stenosis and the Association of Early Intervention With Outcomes

A Systematic Review and Meta-analysis.

This JAMA Cardiology meta-analysis of asymptomatic severe aortic stenosis showed that early intervention may be associated with improved survival compared with conservative management. The analysis fueled the growing debate about expanding intervention indications beyond symptomatic disease.

SGLT2 inhibitors in patients with heart failure with reduced ejection fraction

a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials.

This landmark meta-analysis combined individual patient data from DAPA-HF and EMPEROR-Reduced, confirming that SGLT2 inhibition as a class significantly reduces cardiovascular death and heart failure hospitalization in patients with HFrEF regardless of diabetes status. The analysis cemented SGLT2 inhibitors as the fourth pillar of guideline-directed heart failure therapy.

Effects of glucagon-like peptide-1 receptor agonists on major cardiovascular events in patients with Type 2 diabetes mellitus with or without established cardiovascular disease

a meta-analysis of randomized controlled trials.

This meta-analysis showed that GLP-1 receptor agonists reduce major cardiovascular events in patients with type 2 diabetes both with and without established cardiovascular disease, though the absolute benefit is greater in the secondary prevention population.

Mortality after drug-eluting stents vs. coronary artery bypass grafting for left main coronary artery disease

a meta-analysis of randomized controlled trials.

This meta-analysis comparing mortality after DES versus CABG for left main coronary disease found that CABG was associated with significantly lower long-term all-cause and cardiovascular mortality. The updated data strengthened the evidence favoring surgery for left main revascularization.

2020 Expert Consensus Decision Pathway on Novel Therapies for Cardiovascular Risk Reduction in Patients With Type 2 Diabetes

A Report of the American College of Cardiology Solution Set Oversight Committee.

The 2020 ACC Expert Consensus updated the decision pathway for SGLT2 inhibitors and GLP-1 receptor agonists in type 2 diabetes, integrating evidence from DAPA-HF, CREDENCE, and other contemporary trials to guide agent selection based on predominant cardiovascular or renal comorbidity.

Effect of Genotype-Guided Oral P2Y12 Inhibitor Selection vs Conventional Clopidogrel Therapy on Ischemic Outcomes After Percutaneous Coronary Intervention

The TAILOR-PCI Randomized Clinical Trial.

The TAILOR-PCI trial of genotype-guided P2Y12 inhibitor selection showed a trend toward fewer ischemic events with pharmacogenomic-guided therapy versus standard clopidogrel, though the primary endpoint was not statistically significant. The study advanced the concept of precision antiplatelet therapy.

Evinacumab for Homozygous Familial Hypercholesterolemia.

This pivotal trial showed that evinacumab, an ANGPTL3 inhibitor, reduced LDL cholesterol by 47% in patients with homozygous familial hypercholesterolemia, a condition where conventional therapies including PCSK9 inhibitors are often ineffective due to absent LDL receptors. Evinacumab represents the first LDL-receptor-independent approach to cholesterol lowering.

The Safety and Efficacy of Aspirin Discontinuation on a Background of a P2Y12 Inhibitor in Patients After Percutaneous Coronary Intervention

A Systematic Review and Meta-Analysis.

This meta-analysis confirmed that discontinuing aspirin while continuing a P2Y12 inhibitor after PCI significantly reduces bleeding without increasing ischemic events. The consolidated evidence supported P2Y12 inhibitor monotherapy as a safe de-escalation strategy.

Integrated management of atrial fibrillation in primary care

results of the ALL-IN cluster randomized trial.

The ALL-IN cluster-randomized trial showed that integrated AF management orchestrated in primary care achieved excellent adherence to guideline recommendations and was associated with improved clinical outcomes. The results demonstrated that comprehensive AF care can be effectively delivered in the general practice setting.

2020 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants

A Report of the American College of Cardiology Solution Set Oversight Committee.

The 2020 ACC Expert Consensus on managing bleeding in patients on oral anticoagulants provided practical algorithms for assessment, reversal agent selection, and resumption of anticoagulation after bleeding events, addressing a common clinical challenge.

Complete vs Culprit-Lesion-Only Revascularization for ST-Segment Elevation Myocardial Infarction

A Systematic Review and Meta-analysis.

This JAMA Cardiology meta-analysis confirmed that complete revascularization of nonculprit lesions significantly reduces cardiovascular death and MI compared with culprit-only PCI in patients with STEMI and multivessel disease. The pooled analysis provided definitive evidence favoring the complete revascularization approach.

Association of Radial Artery Graft vs Saphenous Vein Graft With Long-term Cardiovascular Outcomes Among Patients Undergoing Coronary Artery Bypass Grafting

A Systematic Review and Meta-analysis.

This JAMA meta-analysis of individual patient data confirmed that radial artery grafts provide superior long-term cardiovascular outcomes compared with saphenous vein grafts in patients undergoing CABG, supporting the use of arterial conduits to improve coronary bypass durability.

Comparative Efficacy and Safety of Oral P2Y12 Inhibitors in Acute Coronary Syndrome

Network Meta-Analysis of 52 816 Patients From 12 Randomized Trials.

This network meta-analysis of oral P2Y12 inhibitors in ACS incorporating over 52,000 patients from contemporary trials provided updated comparative efficacy and safety data, informing personalized antiplatelet selection based on the balance of ischemic and bleeding risk.

Estimating lifetime benefits of comprehensive disease-modifying pharmacological therapies in patients with heart failure with reduced ejection fraction

a comparative analysis of three randomised controlled trials.

This Lancet analysis estimated the lifetime benefit of comprehensive disease-modifying pharmacotherapy in HFrEF, showing that adding an MRA, ARNI, and SGLT2 inhibitor to standard therapy could yield several additional years of event-free survival. The analysis provided a compelling quantitative rationale for the four-pillar approach to heart failure treatment.

Systemic Amyloidosis Recognition, Prognosis, and Therapy

A Systematic Review.

This JAMA systematic review provided a comprehensive overview of systemic amyloidosis, including AL and ATTR subtypes, covering diagnostic pathways, prognostic assessment, and emerging therapies. The review addressed the growing recognition that cardiac amyloidosis is underdiagnosed.

Effect of Ticagrelor Monotherapy vs Ticagrelor With Aspirin on Major Bleeding and Cardiovascular Events in Patients With Acute Coronary Syndrome

The TICO Randomized Clinical Trial.

The TICO results showed that ticagrelor monotherapy after 3 months of DAPT significantly reduced major bleeding compared with continued ticagrelor plus aspirin at 1 year after PCI for ACS, without increasing cardiovascular events. The study reinforced the safety of early aspirin discontinuation.

Effect of Antihypertensive Medication Reduction vs Usual Care on Short-term Blood Pressure Control in Patients With Hypertension Aged 80 Years and Older

The OPTIMISE Randomized Clinical Trial.

The OPTIMISE trial demonstrated that reducing the number of antihypertensive medications in older patients with well-controlled blood pressure is safe, with the majority maintaining adequate control at 12 weeks. The results supported deprescribing as a reasonable strategy in elderly patients with polypharmacy.

Worldwide Prevalence of Familial Hypercholesterolemia

Meta-Analyses of 11 Million Subjects.

This meta-analysis of 11 million subjects established that familial hypercholesterolemia is far more prevalent than previously estimated, affecting approximately 1 in 250 individuals worldwide and up to 1 in 17 among patients with ischemic heart disease. The data highlighted the massive global underdiagnosis of FH.

Association of Blood Pressure Lowering With Incident Dementia or Cognitive Impairment

A Systematic Review and Meta-analysis.

This JAMA meta-analysis showed that blood pressure lowering is associated with a significant reduction in the risk of incident dementia and cognitive impairment. The findings supported blood pressure control as a potentially modifiable strategy for dementia prevention.

Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction.

The VICTORIA trial demonstrated that vericiguat, a novel oral soluble guanylate cyclase stimulator, reduced the composite of cardiovascular death or heart failure hospitalization in patients with HFrEF who had recently decompensated. This established a new mechanism of action for heart failure treatment, targeting the nitric oxide–sGC–cGMP pathway.

Clinical Management of Stable Coronary Artery Disease in Patients With Type 2 Diabetes Mellitus

A Scientific Statement From the American Heart Association.

This AHA scientific statement addressed the clinical management of stable coronary artery disease specifically in patients with type 2 diabetes, integrating ISCHEMIA results with contemporary evidence on SGLT2 inhibitors and GLP-1 agonists for comprehensive cardiometabolic risk management.

Monotherapy with a P2Y12 inhibitor or aspirin for secondary prevention in patients with established atherosclerosis

a systematic review and meta-analysis.

This Lancet meta-analysis demonstrated that P2Y12 inhibitor monotherapy is superior to aspirin monotherapy for secondary cardiovascular prevention, reducing ischemic events (particularly stroke) without increasing major bleeding. The findings challenged aspirin's position as the default long-term antiplatelet agent.

Ten-Year Outcomes After Drug-Eluting Stents Versus Coronary Artery Bypass Grafting for Left Main Coronary Disease

Extended Follow-Up of the PRECOMBAT Trial.

The EXCEL 10-year extended follow-up showed higher all-cause and cardiovascular mortality with PCI compared with CABG for left main disease, diverging from the earlier 5-year results. The long-term data reignited the debate about the optimal revascularization strategy for left main stenosis.

Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal)

a multicentre, randomised, sham-controlled trial.

The pivotal SPYRAL HTN-OFF MED trial confirmed that catheter-based renal denervation significantly reduced 24-hour ambulatory blood pressure compared with a sham procedure in patients with hypertension not taking antihypertensive medications. This definitive sham-controlled result rehabilitated renal denervation as a genuine blood pressure-lowering intervention.

Optimal Antithrombotic Regimens for Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention

An Updated Network Meta-analysis.

This updated network meta-analysis of antithrombotic regimens in AF patients undergoing PCI, integrating AUGUSTUS, RE-DUAL PCI, PIONEER AF-PCI, and ENTRUST-AF PCI, confirmed that dual therapy with a DOAC plus P2Y12 inhibitor offers the optimal balance of bleeding reduction and ischemic protection.

Clopidogrel versus ticagrelor or prasugrel in patients aged 70 years or older with non-ST-elevation acute coronary syndrome (POPular AGE)

the randomised, open-label, non-inferiority trial.

The POPular AGE trial showed that clopidogrel was associated with less bleeding than ticagrelor or prasugrel in patients aged 70 years and older with non-ST-elevation ACS, without a significant increase in ischemic events. The results supported clopidogrel as the preferred antiplatelet in elderly ACS patients.

Management of Coronary Disease in Patients with Advanced Kidney Disease.

The ISCHEMIA-CKD trial showed that an initial invasive strategy did not reduce cardiovascular events compared with conservative management in patients with stable coronary disease and advanced chronic kidney disease. The findings underscored the heightened procedural risk and attenuated benefit of revascularization in severe CKD.

Inclisiran for the Treatment of Heterozygous Familial Hypercholesterolemia.

The ORION-9 trial demonstrated that twice-yearly inclisiran injections reduced LDL cholesterol by approximately 40% in patients with heterozygous familial hypercholesterolemia on maximally tolerated statin therapy. The results confirmed the efficacy of RNA interference-based lipid lowering in the genetically defined FH population.

Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol.

The ORION-10 and ORION-11 phase 3 trials demonstrated that twice-yearly subcutaneous inclisiran reduced LDL cholesterol by approximately 50% with sustained efficacy and an acceptable safety profile. These results confirmed inclisiran as a viable long-acting approach to LDL lowering, offering an alternative to frequent dosing with statins or monoclonal antibodies.

Effect of Dapagliflozin on Worsening Heart Failure and Cardiovascular Death in Patients With Heart Failure With and Without Diabetes.

This JAMA DAPA-HF analysis confirmed that dapagliflozin reduced worsening heart failure and cardiovascular death equally in patients with HFrEF with and without type 2 diabetes. The finding strengthened the case for SGLT2 inhibitors as a heart failure therapy independent of glycemic status.

Initial Invasive or Conservative Strategy for Stable Coronary Disease.

The ISCHEMIA trial showed that an initial invasive strategy with revascularization did not reduce cardiovascular death or MI compared with optimal medical therapy alone in patients with stable coronary disease and moderate-to-severe ischemia. The findings reinforced medical therapy as a reasonable first-line approach even in the presence of significant ischemia.