The addition of the PCSK9 inhibitor evolocumab to high-intensity cholesterol-lowering regimens significantly reduces the risk of first major cardiovascular events in adults with atherosclerotic cardiovascular disease or diabetes, according to findings from the international VESALIUS-CV clinical trial. The study represents the first demonstration of improved cardiovascular outcomes with a PCSK9 inhibitor in patients without previous heart attack or stroke who were already receiving intensive lipid-lowering treatment.
After a median follow-up of 4.6 years, participants taking evolocumab experienced a 25% reduction in the risk of coronary heart disease death, heart attack, or ischemic stroke compared to those receiving placebo. The study also found a 19% reduction in the risk of coronary heart disease death, heart attack, ischemic stroke, or arterial revascularization. Additional benefits included a 27% reduction in cardiovascular death, heart attack, or ischemic stroke and a 36% reduction in heart attack alone.
Lead study author Erin A. Bohula, M.D., D.Phil., noted that the magnitude of cardiovascular benefit per unit of LDL-C reduction aligns with findings from statin trials described by the Cholesterol Treatment Trialists' Collaboration. The longer follow-up period in this study compared to prior PCSK9 inhibitor trials may have captured more comprehensive clinical benefits, as there is typically a delay in the onset of cardiovascular benefits from LDL-C lowering.
The trial included 12,257 adults with an average age of 66 years from 33 countries, conducted at 745 healthcare sites between June 2019 and November 2021. Participants had LDL-C levels of at least 90 mg/dL and either atherosclerotic cardiovascular disease or high-risk diabetes with additional cardiovascular risk factors, but no history of major cardiovascular events. At enrollment, the median LDL-C level was 115 mg/dL, which decreased by nearly 55% to 45 mg/dL in the evolocumab group after 48 weeks, while placebo group levels remained elevated at 109 mg/dL.
The findings support intensive LDL-C lowering to achieve targets around 40 mg/dL for preventing first major cardiovascular events. The study was simultaneously published as a full, peer-reviewed manuscript in The New England Journal of Medicine. Additional information about cardiovascular disease prevention and treatment is available through the American Heart Association at https://www.heart.org, and detailed guidelines can be found in the 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease at https://www.ahajournals.org/doi/10.1161/CIR.0000000000000678.
