Adding Repatha Treatment to Lipid-Lowering Therapy Shown to Reduce Risk of First Major Adverse Cardiovascular Events

The addition of the proprotein convertase subtilisin/Kexin type 9 (PCSK9) enzyme inhibitor Repatha (evolocomab; Amgen, Thousand Oaks, CA) to standard low-density lipoprotein cholesterol (LDL-C)–lowering therapy for people with atherosclerosis or diabetes but no previous myocardial infarction or stroke was shown to reduce risk for first major cardiovascular event in findings from the VESALIUS-CV clinical trial (NCT03872401), published in The New England Journal of Medicine and presented at the 2025 American Heart Association Scientific Sessions.

VESALIUS-CV was an international, double-blind, placebo-controlled trial that included 12,257 participants with elevated LDL-C levels (≥90 mg/dL) who had diabetes or atherosclerosis and no previous myocardial infarction or stroke. The study population was randomized 1:1 to receive Repatha 140 mg or placebo as a subcutaneous injection every 2 weeks in addition to continuing their LDL-C–lowering therapy. The coprimary end points measured reductions in major adverse cardiovascular events (MACE) including 3-point MACE (composite of death from coronary heart disease, myocardial infarction, or ischemic stroke) and 4-point MACE (composite of 3-point MACE or ischemia-driven arterial revascularization).

Over a median 4.6 years of follow-up, key findings for the coprimary end points include the following:

• Participants treated with Repatha showed a 25% relative reduction in risk of 3-point MACE compared with those receiving placebo.
• Participants treated with Repatha showed a 19% relative reduction in risk of 4-point MACE compared with those receiving placebo.

Additionally, compared with placebo, participants treated with Repatha showed:

• 36% lower risk of myocardial infarction.
• 27% lower risk of composite of death from coronary heart disease or myocardial infarction.
• 27% lower risk of death from cardiovascular causes, ischemic stroke, or myocardial infarction.

Safety outcomes were similar between groups, with no increase in adverse events leading to treatment discontinuation. The authors note that the absolute risk reduction observed over longer follow-up aligns with reductions seen in statin trials, supporting early, intensive LDL lowering for primary prevention in high-risk populations.

Source: Bohula EA, Marston NA, Bhatia AK, et al. Evolocumab in patients without a previous myocardial infarction or stroke. N Engl J Med. Published online November 8, 2025. doi:10.1056/NEJMoa2514428.

Amgen. Amgen’s Repatha cuts risk of first major adverse cardiovascular events by 25% in landmark phase 3 VESALIUS-CV trial. Amgen. Published November 8, 2025. Accessed November 14, 2025. https://www.amgen.com/newsroom/press-releases/2025/11/amgens-repatha-cuts-risk-of-first-major-adverse-cardiovascular-events-by-25-in-landmark-phase-3-vesaliuscv-trial