Abstract Body (Do not enter title and authors here): BACKGROUND: Evolocumab, a fully human monoclonal antibody inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9i) that lowers LDL-C by about 60%, has been shown to reduce the risk of major adverse cardiovascular events in patients with established atherosclerotic cardiovascular disease (ASCVD) with a prior MI, prior stroke, or symptomatic peripheral artery disease, with no offsetting safety concerns. The effect of evolocumab on CV outcomes in lower risk patients without a history of MI or stroke has not been explored.
STUDY DESIGN: VESALIUS-CV (NCT03872401) is a randomized, double-blind, placebo-controlled, global clinical trial designed to evaluate the effect of evolocumab on the risk of major cardiovascular events in patients at high cardiovascular risk but without a prior ischemic event. The study population consists of 12,301 patients with atherosclerosis or high-risk diabetes mellitus without a prior MI or stroke; an LDL-C ≥ 90 mg/dL, or non-high-density lipoprotein cholesterol (non-HDL-C) ≥ 120 mg/dL, or apolipoprotein-B (Apo-B) ≥ 80 mg/dL; and treated with optimized lipid-lowering therapy. Patients were randomized in a 1:1 ratio to evolocumab 140mg subcutaneously every 2 weeks or matching placebo (Figure 1). The primary efficacy objective is to assess whether evolocumab reduces the risk of the dual primary composite endpoints of coronary heart disease (CHD) death, myocardial infarction (MI), or ischemic stroke (triple primary endpoint) and of CHD death, MI, ischemic stroke or ischemia-driven arterial revascularization (quadruple primary endpoint). Recruitment occurred between June 2019 and November 2021. Among those enrolled, the mean age is 65 years, 42% are women, approximately two-thirds have atherosclerosis, 58% have diabetes, the median baseline LDL-C and Apo-B are 122 and 101 mg/dl, respectively, and 73% are on a high-intensity lipid-lowering regimen. End of study was triggered after accrual of a minimum of 751 triple endpoint events, 1254 quadruple endpoint events and 4.5 years median follow-up. Database lock is anticipated in late-September 2025. The primary results will be reported at the time of presentation.
CONCLUSION: VESALIUS-CV will determine whether the addition of evolocumab to optimized lipid lowering therapy reduces cardiovascular events in patients at high cardiovascular risk without a prior MI or stroke.