PCSK9 Inhibitor Shows Significant Cardiovascular Risk Reduction in High-Risk Patients Without Prior Heart Events
The VESALIUS-CV trial demonstrates that evolocumab reduces major cardiovascular events by 25% in patients with atherosclerotic disease or diabetes who haven't had prior heart attacks or strokes, potentially expanding preventive treatment options for millions at risk.
Adding the PCSK9 inhibitor evolocumab to existing cholesterol treatment significantly reduced the risk of first major cardiovascular events in adults with atherosclerotic cardiovascular disease or diabetes who had no history of heart attack or stroke, according to results from the international VESALIUS-CV clinical trial presented at the American Heart Association's Scientific Sessions 2025. The findings, simultaneously published in The New England Journal of Medicine, represent the first demonstration of improved cardiovascular outcomes with a PCSK9 inhibitor in patients without previous heart attacks or strokes who were already receiving high-intensity lipid-lowering regimens.
After an average follow-up of 4.6 years, patients receiving 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 showed 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 among evolocumab-treated participants.
Lead study author Erin A. Bohula, M.D., D.Phil., of Harvard Medical School and Brigham & Women's Hospital, 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 extended follow-up period in this study, compared to prior PCSK9 inhibitor trials, likely captured the long-term clinical benefits that emerge gradually with LDL-C lowering. The findings support intensive LDL-C lowering to achieve targets around 40 mg/dL for preventing first major cardiovascular events.
The trial included 12,257 adults with an average age of 66 years from 33 countries, with 43% being women and 93% self-identifying as white. Participants had atherosclerotic cardiovascular disease or high-risk diabetes with at least one additional cardiovascular risk factor, but no prior heart attack or stroke. At enrollment, the median LDL-C level was 115 mg/dL, which decreased by nearly 55% to 45 mg/dL at 48 weeks in the evolocumab group, while remaining elevated at 109 mg/dL in the placebo group. The American Heart Association provides comprehensive information about atherosclerotic cardiovascular disease and cholesterol management at https://www.heart.org.
Study limitations included a small percentage of patients not receiving cholesterol-lowering treatment at baseline and limited racial and ethnic diversity in the participant population. The researchers emphasized the need for future studies including more diverse populations to confirm these findings across different demographic groups. Despite these limitations, the results suggest that long-term PCSK9 inhibition can improve cardiovascular morbidity and potentially reduce mortality over time in high-risk patients without prior major cardiovascular events.