Evolocumab Cuts First Heart Events by 25% in High-Risk Patients

In a groundbreaking development for cardiovascular medicine, the international VESALIUS-CV clinical trial has demonstrated that the PCSK9 inhibitor evolocumab significantly reduces the risk of first major cardiovascular events in high-risk patients. The study, presented at the American Heart Association's Scientific Sessions 2025 and simultaneously published in The New England Journal of Medicine, followed 12,257 adults with atherosclerotic cardiovascular disease (ASCVD) or diabetes who had no prior history of heart attack or stroke. Over a median follow-up period of 4.6 years, patients receiving evolocumab experienced a remarkable 25% reduction in the risk of coronary heart disease death, heart attack, or ischemic stroke compared to those receiving placebo.

The trial results represent a major advancement in preventive cardiology, as this marks the first demonstration of improved cardiovascular outcomes with a PCSK9 inhibitor in patients without previous major cardiac events who were already on high-intensity lipid-lowering regimens. Lead study author Dr. Erin A. Bohula from Harvard Medical School and Brigham & Women's Hospital emphasized the significance of these findings, noting that the magnitude of cardiovascular benefit per unit of LDL-C reduction aligns with what has been observed in statin trials. The study also showed a 19% reduction in the composite endpoint of coronary heart disease death, heart attack, ischemic stroke, or arterial revascularization, along with a 36% reduction in heart attacks specifically. Notably, the trial included patients with peripheral artery disease and other forms of ASCVD, broadening the potential application of these findings across various cardiovascular conditions.

Beyond the primary endpoints, the study revealed compelling secondary benefits including a 27% reduction in cardiovascular death, heart attack, or ischemic stroke, and nominally lower rates of both cardiovascular death and all-cause mortality in the evolocumab group. The lipid-lowering effects were substantial, with evolocumab reducing LDL cholesterol by nearly 55% from baseline levels of 115 mg/dL to a median of 45 mg/dL at 48 weeks, while placebo patients maintained elevated levels around 109 mg/dL. Conducted across 745 healthcare sites in 33 countries, the trial's findings support intensive LDL-C lowering to targets around 40 mg/dL for preventing first major cardiovascular events, though researchers acknowledge limitations including the need for more diverse racial and ethnic representation in future studies.