Amgen’s Repatha significantly reduces first major cardiovascular events in high-risk patients with diabetes, with Phase 3 VESALIUS-CV data highlighting the benefits of early and intensive LDL-C lowering.
Written By: Sana Khan BPharm
Reviewed By: Pharmacally Editorial Team
Amgen has reported new data showing that Repatha (evolocumab) significantly reduces the risk of first major cardiovascular (CV) events in high-risk primary prevention patients with diabetes but without established atherosclerotic cardiovascular disease (ASCVD). The findings were presented at the American College of Cardiology 75th Annual Scientific Session and simultaneously published in Journal of the American Medical Association.
The results come from a subgroup analysis of 3,655 patients enrolled in the Phase 3 VESALIUS-CV trial (NCT03872401). Over a median follow-up of 4.8 years, adding Repatha to optimized lipid-lowering therapy reduced the risk of the composite endpoint of coronary heart disease (CHD) death, myocardial infarction, or ischemic stroke (3-point MACE) by 31% compared with placebo. A similar 31% reduction was observed for a broader composite endpoint that included ischemia-driven revascularization.
Repatha also delivered substantial LDL-C lowering. Patients receiving the therapy achieved a median LDL-C of 44 mg/dL at 96 weeks, compared to 105 mg/dL in the placebo group, highlighting the benefit of intensive lipid reduction beyond standard therapies such as statins or ezetimibe.
Across secondary endpoints, the therapy showed consistent benefits. Numerical reductions were observed in myocardial infarction (31%), ischemia-driven revascularization (34%), and ischemic stroke (33%). Favorable trends were also seen in mortality outcomes, including reductions in cardiovascular death, CHD death, and all-cause mortality.
According to Jay Bradner of Amgen, the findings reinforce the growing emphasis on earlier and more aggressive LDL-C lowering to prevent first cardiovascular events. The data suggest that targeting LDL-C levels below 45 mg/dL may provide meaningful risk reduction in patients who have not yet developed overt ASCVD.
Similarly, Nicholas Marston highlighted that initiating intensive lipid-lowering therapy earlier in high-risk patients can delay or prevent the clinical onset of heart disease, rather than waiting for plaque progression or a first CV event.
About Repatha and VESALIUS-CV
Repatha is a monoclonal antibody targeting PCSK9, a protein that regulates LDL receptor degradation. By inhibiting PCSK9, the therapy increases LDL receptor recycling and enhances clearance of LDL cholesterol from the bloodstream.
The VESALIUS-CV trial is a global, randomized, placebo-controlled Phase 3 study evaluating evolocumab in more than 12,000 high-risk patients without prior heart attack or stroke. Earlier results, published in the New England Journal of Medicine, demonstrated a 25% reduction in 3-point MACE and a 19% reduction in 4-point MACE.
Clinical Context
Cardiovascular disease remains the leading cause of death globally, with most events occurring in individuals without prior history of heart attack or stroke. Elevated LDL-C is a key modifiable risk factor, and prolonged exposure significantly increases long-term risk, underscoring the importance of early and intensive intervention.
Reference
Repatha® cuts risk of first major cardiovascular events by 31% in high-risk patients without known significant atherosclerosis, 28 March 2026, REPATHA® CUTS RISK OF FIRST MAJOR CARDIOVASCULAR EVENTS BY 31% IN HIGH-RISK PATIENTS WITHOUT KNOWN SIGNIFICANT ATHEROSCLEROSIS | Amgen Inc.
Marston NA, Bohula EA, Bhatia AK, et al. Evolocumab to Reduce First Major Cardiovascular Events in Patients Without Known Significant Atherosclerosis and With Diabetes: Results From the VESALIUS-CV Trial. JAMA. Published online March 28, 2026. https://jamanetwork.com/journals/jama/fullarticle/2847162
Effect of Evolocumab in Patients at High Cardiovascular Risk Without Prior Myocardial Infarction or Stroke (VESALIUS-CV), ClinicalTrials.gov ID NCT03872401, https://clinicaltrials.gov/study/NCT03872401
Erin A. Bohula et al, Evolocumab in Patients without a Previous Myocardial Infarction or Stroke, N Engl J Med 2026;394:117-127, https://www.nejm.org/doi/full/10.1056/NEJMoa2514428
About the Writer
Sana Jamil Khan is a B.Pharm graduate with a strong interest in medical writing and scientific communication. Her work focuses on interpreting clinical research, exploring developments in pharmaceutical science, and presenting complex medical information in a clear and accessible manner. She is particularly interested in topics related to human clinical studies, drug safety observations, and emerging therapeutic research.