Repatha (evolocumab) cuts risk of first major cardiovascular events by 31% in high-risk patientss without known significant atherosclerosis – Amgen

Amgen announced that Repatha (evolocumab), when added to statins or other low-density lipoprotein cholesterol (LDL-C)-lowering treatments, reduced the risk of first major adverse cardiovascular (CV) events (MACE) in high-risk primary prevention patients without known significant atherosclerosis (buildup of plaque in the arteries) and with diabetes. The findings were presented in a late-breaking session at the American College of Cardiology (ACC) 75th Annual Scientific Session and simultaneously published in the Journal of the American Medical Association.

The results are from a new subgroup analysis of 3,655 patients at increased risk of CV events without known significant atherosclerosis (all of whom had diabetes) followed for a median of 4.8 years from the Phase III VESALIUS-CV clinical trial. Results showed Repatha reduced the risk of the composite primary endpoint of coronary heart disease (CHD) death, myocardial infarction or ischemic stroke (3‑P MACE) by 31% compared with placebo. Repatha also reduced the risk of a dual composite primary endpoint that included ischemia‑driven revascularization (4‑P MACE) by 31%. The median achieved LDL-C was 44 mg/dL at 96 weeks in the Repatha added to optimized lipid-lowering therapy arm compared to 105 mg/dL in the placebo plus optimized lipid-lowering therapy arm (548 patients in the subgroup were part of a lipid sub-study).

Across secondary endpoints, Repatha demonstrated consistent benefit, including the following composite endpoints: heart attack, ischemic stroke or any ischemia-driven revascularization; CHD death, heart attack or revascularization; CV death, heart attack or ischemic stroke. Among individual secondary endpoints, Repatha showed numerical reductions in the risk of heart attack by 31%, ischemia-driven revascularization by 34% and ischemic stroke by 33%. Repatha demonstrated numerical trends for reduced mortality rates, including CV death (32% relative risk reduction), CHD death (27% relative risk reduction) and all‑cause death (24% relative risk reduction).

Amgen abstracts and presentation times at the ACC 75th Annual Scientific Session are as follows:

• Evolocumab for the Reduction of First Major Cardiovascular Events in Patients without Significant Atherosclerosis: Results from VESALIUS-CV  LBS.105, Saturday, March 28
• LDL-C Lowering and Associated Risk Reduction of Myocardial Infarction and Stroke-Related Hospitalizations in Patients with ASCVD and Diabetes Abstract #1165-11, Monday, March 30

VESALIUS-CV is a Phase III, double-blind, randomized, placebo-controlled, global clinical trial (NCT03872401) designed to evaluate the impact of LDL-C lowering with evolocumab on MACE in adults at high CV risk without prior heart attack or stroke. Results were published in the New England Journal of Medicine in November 2025. Repatha demonstrated a 25% relative reduction in the risk of a composite of coronary heart disease (CHD) death, heart attack or ischemic stroke (3-P MACE), and 19% reduction in a broader composite that also included any ischemia-driven arterial revascularization (4-P MACE). Repatha also reduced the risk of heart attack by 36%.

VESALIUS-CV enrolled more than 12,000 patients with known ASCVD or high-risk diabetes, who had no history of heart attack or stroke, an LDL-C ≥ 90 mg/dL, or non-high-density lipoprotein cholesterol (non-HDL-C) ≥ 120 mg/dL, or apolipoprotein B ≥ 80 mg/dL; and treated with highest tolerated dose of statin and/or ezetimibe. The median baseline LDL-C was 122 mg/dL (IQR, 104-149 mg/dL) on local lab testing. Participants were randomized to receive Repatha or placebo in addition to optimized lipid-lowering therapy and were followed for a median of approximately 4.6 years.

“The evidence is unequivocal: Intensive LDL-C lowering with Repatha significantly reduces the risk of major CV events for high-risk patients,” said Dr. Jay Bradner, executive vice president of Research and Development at Amgen. “The new ACC/AHA Multisociety Guideline on the Management of Dyslipidemia reinforces the importance of earlier, more intensive lowering of LDL-C to prevent CV events. VESALIUS-CV builds on this, showing that in high-risk patients without prior heart attack or stroke, lowering LDL-C beyond what is typically achieved today can meaningfully reduce risk before ASCVD takes hold. These data also show the benefit of lowering LDL-C below 45 mg/dL with Repatha, a level that may not be achieved with statins or ezetimibe alone. Now is the time to treat earlier and help all appropriate patients reach lower LDL-C goals.”

“This analysis clearly demonstrates that the CV benefit of evolocumab in the VESALIUS-CV study includes those who had no known ASCVD, or significant plaque buildup in the arteries,” said Dr. Nicholas Marston, assistant professor of medicine, member of the TIMI Study Group and cardiologist at Brigham and Women’s Hospital and Harvard Medical School. “Lowering LDL-C earlier with more intensive therapy in high-risk primary prevention patients, before plaque becomes advanced, can prevent the clinical onset of heart disease. These findings confirm the substantial risk reduction that can be achieved by treating more proactively with evolocumab rather than waiting for the development of significant atherosclerosis or a CV event to then intensify lipid-lowering therapy.”

See citations- Bohula EA, Marston NA,  Bhatia AK et al. Evolocumab in Patients without a Previous Myocardial Infarction or Stroke. N Engl J Med 2026, 394:117 DOI: 10.1056/NEJMoa2514428

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. doi:10.1001/jama.2026.3277