VESALIUS-CV: Evolocumab Outperforms Placebo in MACE Prevention in ASCVD and Diabetes

Adding evolocumab, a proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor, to existing high-intensity cholesterol-lowering therapy reduces the risk of a first major cardiovascular event (MACE) among patients with atherosclerotic cardiovascular disease (ASCVD) or diabetes, according to data from the VESALIUS-CV trial.¹

This late-breaking science presentation was given at the American Heart Association’s Scientific Sessions 2025 in New Orleans, Louisiana, by Erin Bohula, MD, assistant professor of medicine, Harvard Medical School, Brigham & Women’s Hospital, and colleagues. It encapsulated the topline results from VESALIUS-CV, an international, double-blind, randomized, placebo-controlled trial.^1,2

“The results from the VESALIUS-CV trial represent the first demonstration of improved cardiovascular outcomes with a PCSK9 inhibitor, or any non-statin for that matter, in patients without a previous heart attack or stroke who are already being treated with a high-intensity lipid-lowering regimen,” Bohula said in a statement.¹

VESALIUS-CV was conducted at 774 sites in 33 countries, including patients who were either 50-79 years (in men) or 55-79 years (in women) with an LDL cholesterol level of ≥90 mg/dL, a non-high-density lipoprotein (non-HDL) cholesterol level of ≥120 mg/dL, or an apolipoprotein B (ApoB) level of ≥80 mg/dL. Additionally, patients were required to have been receiving stable, optimized lipid-lowering therapy for ≥2 weeks prior to enrollment. Patients were excluded if they exhibited a history of myocardial infarction or stroke.²

In addition to these criteria, patients had to meet trial criteria for coronary artery disease, atherosclerotic cerebrovascular disease, peripheral artery disease, or high-risk diabetes. These patients had to have ≥1 additional criterion placing them at higher risk for cardiovascular disease, such as an age of ≥65 years, active smoking, severely elevated lipid levels, or concomitant ASCVD and diabetes.²

Bohula and colleagues randomly assigned patients in a 1:1 ratio to receive either subcutaneous evolocumab 140 mg every 2 weeks or matching placebo. The 2 primary efficacy endpoints of the study were a composite of death from coronary heart disease, myocardial infarction, or ischemic stroke (3-point MACE) and a composite of death from coronary heart disease, myocardial infarction, ischemic stroke, or ischemia-driven arterial revascularization (4-point MACE).²

Ultimately, a total of 12,257 patients were enrolled and randomized, with characteristics consistent between the 2 trial groups. Median age was 66 years (interquartile range, 60-71), and roughly 2/3 of patients met criteria for qualifying atherosclerosis, including 45% with coronary artery disease, 17% with peripheral artery disease, and 10% with cerebrovascular disease.²

Investigators found that evolocumab therapy led to substantially lower risks of both primary efficacy endpoints when compared to placebo. A 3-point MACE event occurred in 336 patients in the evolocumab group and 443 in the placebo arm (HR, 0.75; 95% CI, 0.65-0.86; P <.001), which corresponded to a 25% lower risk. A 4-point MACE event occurred in 747 patients in the evolocumab arm and 907 in the placebo arm (HR, 0.81; 95% CI, 0.73-0.89; P <.001), which translated to a 19% lower risk. Additionally, there was no evidence recorded of a between-group difference in adverse event incidence leading to discontinuation.²

“Together with data from genetic studies of PCSK9 variants and other PCSK9 inhibitor outcomes studies, our findings suggest that long-term lowering with PCSK9 inhibitors can help to improve cardiovascular morbidity and potentially mortality over time,” Bohula said. “The findings also support the use of intensive LDL-C lowering to achieve targets of around 40 mg/dL to help prevent a first major cardiovascular event.”¹

References

1. Kirkwood M. PCSK9 inhibitor reduced major CVD events in adults with no prior heart attack or stroke. American Heart Association Newsroom. November 8, 2025. Accessed November 8, 2025. https://newsroom.heart.org/news/pcsk9-inhibitor-reduced-major-cvd-events-in-adults-with-no-prior-heart-attack-or-stroke

2. Bohula E, Marston N, Bhatia A, et al. Evolocumab in Patients without a Previous Myocardial Infarction or Stroke. NEJM. November 8, 2025. Accessed November 8, 2025. doi:10.1056/NEJMoa2514428