Repatha Reduces First Major Cardiovascular Events by 31% in High-Risk Patients Without Significant Atherosclerosis
核心洞察
Amgen's Repatha (evolocumab) demonstrated a 31% reduction in first major cardiovascular events in high-risk primary prevention patients without significant atherosclerosis in a VESALIUS-CV subgroup analysis.
The study analyzed 3,655 diabetic patients followed for a median of 4.8 years, achieving a median LDL-C (搜索) of 44 mg/dL compared to 105 mg/dL in the placebo group.
Repatha showed consistent benefits across secondary endpoints, including 31% reduction in heart attack risk, 34% reduction in ischemia-driven revascularization, and 33% reduction in ischemic stroke.
Amgen's PCSK9 inhibitor Repatha (evolocumab) demonstrated a 31% reduction in first major adverse cardiovascular events in high-risk primary prevention patients without known significant atherosclerosis, according to new subgroup analysis from the Phase 3 VESALIUS-CV trial presented at the American College of Cardiology 75th Annual Scientific Session and simultaneously published in the Journal of the American Medical Association.
Significant Risk Reduction in Primary Prevention
The analysis examined 3,655 patients at increased cardiovascular risk without known significant atherosclerosis, all of whom had diabetes, followed for a median of 4.8 years. Repatha reduced the risk of the composite primary endpoint of coronary heart disease death, myocardial infarction or ischemic stroke (3-P MACE) by 31% compared with placebo. The drug also achieved a 31% reduction in the broader composite endpoint that included ischemia-driven revascularization (4-P MACE).
"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 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. "Lowering LDL-C (搜索) earlier with more intensive therapy in high-risk primary prevention patients, before plaque becomes advanced, can prevent the clinical onset of heart disease."
Substantial LDL-C Reduction Achieved
The median achieved LDL-C (搜索) was 44 mg/dL at 96 weeks in the Repatha arm compared to 105 mg/dL in the placebo arm among 548 patients in the subgroup who were part of a lipid sub-study. This represents a significant reduction from the median baseline LDL-C of 122 mg/dL across the broader VESALIUS-CV trial population.
"The evidence is unequivocal: Intensive LDL-C (搜索) lowering with Repatha significantly reduces the risk of major CV events for high-risk patients," said Jay Bradner, M.D., executive vice president of Research and Development at Amgen. "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."
Consistent Benefits Across Secondary Endpoints
Across secondary endpoints, Repatha demonstrated consistent benefit in multiple composite measures including heart attack, ischemic stroke or any ischemia-driven revascularization; CHD death, heart attack or revascularization; and CV death, heart attack or ischemic stroke. Among individual secondary endpoints, Repatha showed numerical reductions in heart attack risk by 31%, ischemia-driven revascularization by 34%, and ischemic stroke by 33%.
The drug also demonstrated numerical trends for reduced mortality rates, including cardiovascular death (32% relative risk reduction), CHD death (27% relative risk reduction), and all-cause death (24% relative risk reduction).
VESALIUS-CV Trial Design and Population
VESALIUS-CV is a Phase 3, double-blind, randomized, placebo-controlled, global clinical trial designed to evaluate the impact of LDL-C (搜索) lowering with evolocumab on MACE in adults at high cardiovascular risk without prior heart attack or stroke. The full trial 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 ≥ 120 mg/dL, or apolipoprotein B ≥ 80 mg/dL, and were treated with the highest tolerated dose of statin and/or ezetimibe.
Results from the overall VESALIUS-CV trial, published in the New England Journal of Medicine in November 2025, showed Repatha demonstrated a 25% relative reduction in the risk of 3-P MACE and 19% reduction in 4-P MACE, with a 36% reduction in heart attack risk.
Clinical Significance and Market Position
Cardiovascular disease remains the leading cause of death worldwide, with most cardiovascular events occurring in people without a prior history of heart attack or stroke. High LDL-C (搜索) is one of the most modifiable risk factors for heart attack and stroke, and prolonged exposure to elevated LDL-C increases cardiovascular risk over time, making earlier and more intensive LDL-C lowering critical to reducing the risk of a first cardiovascular event.
Repatha is the only PCSK9 inhibitor to demonstrate a significant reduction of cardiovascular events in both high-risk primary and secondary prevention. The drug was first approved in 2015 and has since been used by more than 8 million patients globally. In August 2025, the U.S. Food and Drug Administration broadened the approved use of Repatha to include adults at increased risk for major adverse cardiovascular events due to uncontrolled LDL-C (搜索).
The clinical benefits and safety of Repatha have been studied for 15 years in 51 clinical trials with over 57,000 patients. Repatha has been prescribed to over 8 million patients globally and is approved in 74 countries, including the U.S., Japan, Canada and in all 28 countries that are members of the European Union.