Effect of Evolocumab in Patients at High Cardiovascular Risk without Prior Myocardial Infarction or Stroke - VESALIUS-CV

Nov 21, 2025

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Author/Summarized by Author:
Carlos A Vergara Sanchez, MD
Summary Reviewer:
Fred M. Kusumoto, MD, FACC; R. Scott Wright, MD, FACC
Original Posted Date:
11/21/2025
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Contribution To Literature:

Compared with placebo, PCSK9 inhibition with evolocumab reduced the risk of first cardiovascular events among patients with atherosclerosis or diabetes and without a previous myocardial infarction or stroke, based on findings from the VESALIUS-CV trial.

Study Design:

  • Population: 12,257 patients with established atherosclerosis without previous myocardial infarction (MI) or stroke
  • Duration of follow-up: Median of 4.6 years
  • Median patient age: 66 years
  • Intervention:
    • Treatment group: Evolocumab 140 mg every two weeks
    • Control group: Optimal lipid-lowering therapy + placebo
  • Demographics (i.e., gender and race, etc.):
    • Race/ethnicity: 93% White, 17% Hispanic
    • Gender: 43% women
    • Comorbidities:
      • 45% with coronary artery disease.
      • 10% cerebrovascular disease
      • 17% peripheral artery disease
      • 60% had diabetes (49% high risk diabetes)

Principal Findings:

Primary outcome:

  • 3-point major adverse cardiovascular events (MACE) (coronary heart disease [CHD] death, MI, ischemic stroke):
    • Evolocumab: 336 patients (6.2%)
    • Placebo: 443 patients (8.0%)
    • Hazard Ratio (HR) 0.75 (95% CI: 0.65–0.86; p<0.0001)
  • 4-point MACE (above + ischemia-driven revascularization):
    • Evolocumab: 747 patients (13.4%)
    • Placebo: 907 patients (16.2%)
    • HR 0.81 (95% CI, 0.73–0.89; p<0.001)
  • Safety: No significant difference in adverse events between groups.

Secondary outcomes:

    • MI, stroke, or ischemia-driven revascularization: HR 0.79 (95% CI: 0.72–0.88; p<0.001)
    • CHD death, MI, or ischemia-driven revascularization: HR 0.79 (95% CI: 0.72–0.88; p<0.001)
    • CHD death, MI, stroke: HR 0.73 (95% CI: 0.64–0.84; p<0.001)
    • CHD death + MI: HR 0.73 (95% CI: 0.62–0.87; p<0.001)
    • MI alone: HR 0.64 (95% CI: 0.52–0.79; p<0.001)
    • Ischemia-driven revascularization: HR 0.79 (95% CI: 0.70–0.88; p<0.001)

Lipid substudy:

  • Participants: 2,014 patients.
  • Baseline low-density lipoprotein cholesterol (LDL-C): Median LDL 115 mg/dL
  • At 48 weeks:
    • LDL-C reduction: 55%
    • Absolute reduction: 63 mg/dL
    • Median LDL-C:
      • Evolocumab 45 mg/dL
      • Placebo 109 mg/dL


Interpretation:

Evolocumab significantly reduced the risk of MACE (3- and 4-point MACE) in patients with established atherosclerosis and no previous MI or stroke. The trial recruited a mainly White population, with almost half of the participants being women. There was minimal loss to follow-up and the median LDL-C achieved was 45 mg/dL in the intervention group. The results of this trial further clarify the potential benefit of using PCSK9 inhibitors, in addition to other lipidlowering therapies when goal LDL-C is not reached. Further research is needed to assess its role in populations without established atherosclerosis as a true primary prevention therapy. The evidence of this trial further supports lower LDL-C targets, especially in those without symptomatic atherosclerotic cardiovascular disease as an additional way to favorably modify the disease process.

References

Bohula EA, Marston NA, Bhatia AK, et al. Evolocumab in Patients without a Previous Myocardial Infarction or Stroke. N Engl J Med. Published online Nov. 8, 2025. doi:10.1056/nejmoa2514428.

Presented by Erin Ann Bohula, MD, DPhil, FACC, at the American Heart Association Scientific Sessions (AHA 2025), New Orleans, LA, Nov. 8, 2025.

Resources

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention

Keywords: AHA Annual Scientific Sessions, AHA25, Dyslipidemias, Secondary Prevention