LDL cholesterol is a well-established factor for cardiovascular disease. Therapy with PCSK9 inhibitors, including evolocumab, has been shown to reduce the risk of cardiovascular events in patients with a history of major events such as acute myocardial infarction (MI) or stroke. However, its role in primary prevention — in high-risk individuals without prior events — remained uncertain.
The VESALIUS-CV study was a randomized, double-blind, placebo-controlled, global trial. It enrolled 12,257 patients without prior MI or stroke, with atherosclerotic disease or high-risk diabetes, and LDL-C ≥90 mg/dL, non-HDL-C ≥120 mg/dL, or ApoB ≥80 mg/dL, all on optimized lipid-lowering therapy (± ezetimibe). Participants were randomized to evolocumab 140 mg SC every 2 weeks or placebo.
The primary endpoints were 3-point major adverse cardiovascular events (MACE: death from ischemic heart disease, MI, or ischemic stroke) and 4-point MACE (3-P MACE + ischemia-driven revascularization). The mean age was 66 years, 43% of subjects were women, and 58% had diabetes. Following treatment with evolocumab, LDL-C decreased by 55% (absolute reduction of 63 mg/dL; p <0.0001).
In terms of clinical outcomes, the incidence of 3-P MACE was 6.2% vs. 8.0% (hazard ratio [HR] 0.75; 95% confidence interval [CI] 0.65–0.86; p<0.0001), and for 4-P MACE, 13.4% vs. 16.2% (HR 0.81; 95% CI 0.73–0.89; p<0.0001). All-cause mortality was 7.9% vs. 9.7% (HR 0.80; 95% CI 0.70–0.91).
Conclusions
In high-cardiovascular-risk patients without prior MI or stroke, adding evolocumab to optimized lipid-lowering therapy significantly reduced the incidence of MACE (25% for 3-P and 19% for 4-P), achieving LDL-C levels around 45 mg/dL, with a favorable safety profile and consistent results.
Presented by Erin Bohula during the Late-Breaking Science session at AHA 2025, New Orleans, USA.
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