Repatha Cuts Risk of First Major Cardiovascular Events by 31% in High-Risk Patients Without Known Significant Atherosclerosis

Repatha is the Only PCSK9 Inhibitor to Significantly Reduce the Risk of First CV Events in High-Risk Primary Prevention

Mar. 28, 2026 at 9:06pm

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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 and with diabetes. The findings were presented at the American College of Cardiology (ACC) 75th Annual Scientific Session and published in the Journal of the American Medical Association.

Why it matters

Cardiovascular disease (CVD) is the leading cause of death worldwide, and most CV events occur in people without a prior history of heart attack or stroke. High LDL-C is one of the most modifiable risk factors for heart attack and stroke, and prolonged exposure to elevated LDL‑C increases CV risk over time, making earlier and more intensive LDL‑C lowering critical to reducing the risk of a first CV event.

The details

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 3 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.

  • The VESALIUS-CV trial enrolled patients between 2020 and 2024.
  • Patients were followed for a median of 4.8 years.

The players

Repatha

A human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9) and is used to reduce the risk of major adverse cardiovascular events and lower LDL-C.

VESALIUS-CV

A Phase 3, double-blind, randomized, placebo-controlled, global clinical trial 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.

Jay Bradner, M.D.

Executive vice president of Research and Development at Amgen.

Nicholas Marston, M.D., M.P.H.

Assistant professor of medicine, member of the TIMI Study Group and cardiologist at Brigham and Women's Hospital and Harvard Medical School.

Amgen

A biotechnology company that discovers, develops, manufactures and delivers innovative medicines to fight some of the world's toughest diseases.

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What they’re saying

“The evidence is unequivocal: Intensive LDL-C lowering with Repatha significantly reduces the risk of major CV events for high-risk patients.”

— Jay Bradner, M.D., Executive vice president of Research and Development at Amgen

“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. 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.”

— Nicholas Marston, M.D., M.P.H., Assistant professor of medicine, member of the TIMI Study Group and cardiologist at Brigham and Women's Hospital and Harvard Medical School

The takeaway

These data 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. Treating high-risk patients earlier and helping them reach lower LDL-C goals can meaningfully reduce their risk of cardiovascular events before atherosclerosis takes hold.