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November 8, 2025New England Journal of Medicine
Evolocumab in Patients without a Previous Myocardial Infarction or Stroke
Erin A. BohulaNicholas MarstonAjay BhatiaGaetano Maria De FerrariLawrence A. LeiterJosé Carlos NicolauJeong-Gun ParkJulia KuderSabina A. MurphyEdward P. WalshHuei WangV. BláhaAndrzej BudajJan H. CornelAssen GoudevRóbert Gábor KissAlberto LorenzattiAlexander ParkhomenkoMarcoli CyrilleGabriel Paiva da Silva LimaE. Magnus OhmanRobert P. GiuglianoMarc S. Sabatine
Key result
Evolocumab cuts 3-point MACE ~25% vs. placebo in patients without prior MI or stroke.
- HR 0.75
- 95% CI 0.65 to 0.86
- P<0.001
- n=12,257
Why the study?
The effect of evolocumab on the risk of major adverse cardiovascular events among patients without a previous myocardial infarction or stroke was unknown.
Does evolocumab reduce the risk of major adverse cardiovascular events in patients with atherosclerosis or diabetes and without a previous myocardial infarction or stroke?
Study Design
Type
RCT (n=12,257)
Blinding
double-blind
Randomization
1:1 ratio
Multicenter
Yes
Structured PICO
Does evolocumab reduce the risk of major adverse cardiovascular events in patients with atherosclerosis or diabetes and without a previous myocardial infarction or stroke?
P
Population
12,257 patients (median age 66, 43% women) with atherosclerosis or diabetes and without a previous myocardial infarction or stroke, followed for a median of 4.6 years.
I
Intervention
Evolocumab 140 mg every 2 weeks
C
Comparator
Placebo
O
Outcome
Two primary end points: a composite of death from coronary heart disease, myocardial infarction, or ischemic stroke (3-point MACE) and a composite of 3-point MACE or ischemia-driven arterial revascularization (4-point MACE)composite
Main Result
Hazard Ratio: 0.75 (95% CI 0.65–0.86)
Absolute Event Rate: 6.2% vs 8%
p-value: p=<0.001
Discussion
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Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
CEChiadi E. NdumeleCardiologist, Editorialist
“Like its namesake, the VESALIUS-CV trial advances our understanding of vascular anatomy -- this time, by showing the important implications of strategies to prevent atherosclerotic cardiovascular disease. The findings represent an important step forward in clinical knowledge.”
PBPamela B. MorrisPreventive Cardiologist, Discussant
“What this does for us is begin to expand the populations who are likely to benefit from more intensive lipid lowering therapy beyond those ASCVD and acute coronary syndrome patients, into those without prior MI, subclinical atherosclerosis, and high-risk diabetes. I think what this trial demonstrates is that more intensive lipid-lowering therapy even earlier in the course of disease is better to reduce ischemic events.”
“The results from the VESALIUS-CV trial represent the first demonstration of improved cardiovascular outcomes with a PCSK9 inhibitor, or any non-statin therapy, in a population without prior MI or stroke.”
Implication
Evolocumab significantly reduces the risk of first cardiovascular events in patients with atherosclerosis or diabetes and without a prior MI or stroke.
Abstract
BACKGROUND: The proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor evolocumab reduces the risk of major adverse cardiovascular events (MACE) among patients with a previous myocardial infarction, stroke, or symptomatic peripheral artery disease. The effect of evolocumab on the risk of MACE among patients without a previous myocardial infarction or stroke is unknown. METHODS: We conducted an international, double-blind, randomized, placebo-controlled trial of evolocumab in patients with atherosclerosis or diabetes and without a previous myocardial infarction or stroke who had a low-density lipoprotein cholesterol level of at least 90 mg per deciliter. Patients were randomly assigned in a 1:1 ratio to receive evolocumab at a dose of 140 mg every 2 weeks or placebo. The two primary end points were a composite of death from coronary heart disease, myocardial infarction, or ischemic stroke (3-point MACE) and a composite of 3-point MACE or ischemia-driven arterial revascularization (4-point MACE). RESULTS: A total of 12,257 patients were randomly assigned to receive evolocumab (6129 patients) or placebo (6128) and were included in the efficacy analyses. The median age of the patients was 66 years, 43% were women, and 93% were White. The median follow-up was 4.6 years. A 3-point MACE event occurred in 336 patients (5-year Kaplan-Meier estimate, 6.2%) in the evolocumab group, as compared with 443 (8.0%) in the placebo group (hazard ratio, 0.75; 95% confidence interval [CI], 0.65 to 0.86; P<0.001). A 4-point MACE event occurred in 747 patients (5-year Kaplan-Meier estimate, 13.4%) in the evolocumab group, as compared with 907 (16.2%) in the placebo group (hazard ratio, 0.81; 95% CI, 0.73 to 0.89; P<0.001). No evidence of a between-group difference was seen in the incidence of safety events. CONCLUSIONS: PCSK9 inhibition with evolocumab led to a lower risk of first cardiovascular events than placebo among patients with atherosclerosis or diabetes and without a previous myocardial infarction or stroke. (Funded by Amgen; VESALIUS-CV ClinicalTrials.gov number, NCT03872401.).
Cite This Study
Bohula et al. (2025) conducted an RCT in Atherosclerosis or diabetes without a previous myocardial infarction or stroke (n=12,257). Evolocumab vs. Placebo was evaluated on Composite of death from coronary heart disease, myocardial infarction, or ischemic stroke (3-point MACE) (HR 0.75, 95% CI 0.65 to 0.86, p=<0.001). Evolocumab reduced the risk of 3-point MACE (6.2% vs 8.0%; HR 0.75; P<0.001) and 4-point MACE (13.4% vs 16.2%; HR 0.81; P<0.001) compared to placebo in patients without prior MI or stroke.