Phase 3 VESALIUS-CV Trial Demonstrates Evolocumab Reduces Cardiovascular Events in High-Risk Adults Without Prior Heart Attack or Stroke

The phase 3 VESALIUS-CV trial met its primary endpoints, showing that evolocumab (Repatha®, Amgen) significantly reduced the risk of major adverse cardiovascular events (MACE) in adults without a prior history of myocardial infarction or stroke, Amgen announced October 2, 2025. Evolocumab is now the first proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor to demonstrate event reduction in both primary and secondary prevention settings.1

The global, double-blind, randomized trial enrolled more than 12 000 high-risk patients, approximately 85% of whom were already receiving high- or moderate-intensity statins or other lipid-lowering therapy. Participants were followed for a median of 4.5 years. Primary endpoints were the time to first occurrence of a composite of coronary heart disease (CHD) death, myocardial infarction, or ischemic stroke, and the time to first occurrence of a composite of CHD death, myocardial infarction, ischemic stroke, or any ischemia-driven arterial revascularization. Both endpoints were met with statistically and clinically significant reductions in events. No new safety signals were observed.1

"These results mark an important milestone in the fight against cardiovascular disease, the leading cause of death worldwide. The benefit across endpoints and established safety profile underscore Repatha's role as a cornerstone therapy in comprehensive lipid management," Jay Bradner, MD, executive vice president of Research and Development at Amgen, said in a press release.1

Evolocumab, a monoclonal antibody that inhibits PCSK9, is known as an effective low-density lipoprotein cholesterol (LDL-C) lowering therapy. Earlier this year, the US Food and Drug Administration broadened the approved use of evolocumab to include adults at increased risk for MACE due to uncontrolled LDL-C. The VESALIUS-CV findings build on this expanded indication, reinforcing the role of evolocumab in earlier intervention to reduce risk in high-risk populations.1,2

The results also extend evidence beyond the FOURIER trial, which in 2017 showed evolocumab reduced CV events in patients with established atherosclerotic cardiovascular disease (ASCVD) and prior events. VESALIUS-CV demonstrates similar benefits in patients without prior events but with elevated risk due to ASCVD or diabetes.1

Cardiovascular disease remains the leading cause of death worldwide, with approximately 75% of heart attacks and strokes occurring as first-time events. Despite optimized lipid-lowering therapy, more than 80% of high-risk patients remain above guideline-recommended LDL-C targets.

"Repatha is known as a highly effective LDL-C lowering treatment and is now the first and only PCSK9 inhibitor shown to reduce cardiovascular events in high-risk adults without prior heart attack or stroke. These additional data demonstrate that Repatha has the potential to reach tens of millions more patients earlier in their journey, before a life-altering event occurs," Bradner added in the release.1

Full results of VESALIUS-CV will be presented November 8 at the American Heart Association Scientific Sessions and submitted for peer-reviewed publication.1

Evolocumab was first approved in 2015 and is currently indicated to reduce the risk of MACE in adults, and as an adjunct to diet and exercise for adults and pediatric patients with familial hypercholesterolemia. It has been studied in more than 57 000 patients across 51 trials.1

References:

1. Landmark phase 3 trial (VESALIUS-CV) meets primary endpoints in a cardiovascular primary prevention study of 12,000 patients. Amgen. October 2, 2025. Accessed October 2, 2025. https://investors.amgen.com/news-releases/news-release-details/landmark-phase-3-trial-vesalius-cv-meets-primary-endpoints
2. Jennings S. FDA expands evolocumab indication to adults at risk for major cardiovascular events due to uncontrolled LDL-C. Patient Care. August 26, 2025. Accessed October 2, 2025. https://www.patientcareonline.com/view/fda-expands-evolocumab-indication-to-adults-at-risk-for-major-cardiovascular-events-due-to-uncontrolled-ldl-c