Low-density lipoprotein cholesterol (LDL-C) is a well-established modifiable cardiovascular risk factor. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors lower LDL-C and have been shown to reduce the risk of recurrent cardiovascular events in patients with a history of a prior major cardiovascular event, such as MI or stroke
The Effect of Evolocumab in Patients at High Cardiovascular Risk Without Prior MI or Stroke: Primary Results of the VESALIUS-CV trial evaluated if Evolocumab, a PCSK9 inhibitor, could reduce the risk of a first major cardiovascular event in a lower-risk population than previously studied. The global randomized phase 3 double-blind, placebo-controlled trial that included 12,257 patients with known atherosclerotic cardiovascular disease (ASCVD) or diabetes but without a history of heart attack or stroke. Patients had either LDL-C ≥90 mg/dL, non-high-density lipoprotein cholesterol (non-HDL-C) ≥120 mg/dL or apolipoprotein B ≥80 mg/dL and had been treated with optimized lipid-lowering therapy. Participants were randomized to receive Evolocumab or placebo in addition to continuing to receive optimized lipid-lowering therapy and followed for a median of 4.6 years.
Evolocumab significantly reduced the risk of the dual primary endpoints with a 25% reduction in coronary heart disease death, MI or ischemic stroke and a 19% reduction in the expanded endpoint that included ischemia-driven arterial revascularization compared to placebo. Findings for the dual primary endpoints were consistent across key subgroups, including in those with diabetes without qualifying atherosclerosis, which represented approximately one third of the study population. Evolocumab also reduced the risk of multiple secondary endpoints, including a 27% reduction in cardiovascular death, MI or ischemic stroke and a 36% reduction in MI.
“Results from VESALIUS-CV represent the first demonstration of improved cardiovascular outcomes with a PCSK9 inhibitor, or any non-statin for that matter, in patients without a prior MI or stroke already treated with a high-intensity lipid-lowering regimen,” said principal investigator Erin Bohula, MD, DPhil, an associate physician in cardiovascular medicine at Brigham and Women’s Hospital and assistant professor of medicine at Harvard Medical School. The study was simultaneously published in The New England Journal of Medicine.
Our findings support the use of intensive LDL-C lowering to achieve targets of ~40mg/dL even in the lower risk patients, like those included in the VESALIUS-CV study without a prior major cardiovascular event of MI or stroke to prevent the first major cardiovascular event she said
