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.
Whether digitalis glycosides retain a role in heart failure with reduced or mildly reduced ejection fraction (HF(m)rEF) on top of contemporary guideline-directed medical therapy is debated.
This study-level meta-analysis combined the DECISION (n=1001), DIGIT-HF (~1240) and DIG (n=6800) trials, totalling 9013 patients with HF(m)rEF assigned to digoxin, digitoxin or placebo. The primary outcome was a composite of cardiovascular death or first worsening heart failure event. Secondary analyses examined time to first worsening heart failure event and pre-specified interaction with guideline-recommended medical therapy use across the RALES, EMPHASIS-HF, PARADIGM-HF and DAPA-HF backbones.
Compared with placebo, digitalis glycosides significantly reduced the primary composite (HR 0.85; 95% CI 0.80–0.90; p<0.001) and the time to first worsening heart failure event (HR 0.75; 95% CI 0.69–0.81; p<0.001). The benefit was consistent across trials and was maintained in patients already on contemporary guideline-recommended HF therapy, with no heterogeneity by trial type or glycoside variant.
At the population level, digitalis glycosides reduce worsening heart failure events on top of contemporary guideline-directed therapy, supporting reconsideration of their place in HF(m)rEF treatment.
