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Evolocumab in Patients without a Previous Myocardial Infarction or Stroke
Erin A Bohula1, Nicholas A Marston1, Ajay K Bhatia2
1Thrombolysis in Myocardial Infarction (TIMI) Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston.
Insights
Evolocumab, a PCSK9 inhibitor, significantly lowered cardiovascular event risk in patients with atherosclerosis or diabetes but no prior heart attack or stroke. This study demonstrates its efficacy in preventing major adverse cardiovascular events (MACE) in a new patient cohort.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
Background:
- Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, like evolocumab, are known to reduce major adverse cardiovascular events (MACE) in patients with established cardiovascular disease.
- The impact of evolocumab on MACE risk in patients without a history of myocardial infarction or stroke was previously unestablished.
Purpose of the Study:
- To evaluate the efficacy of evolocumab in reducing cardiovascular events in patients with atherosclerosis or diabetes but no prior myocardial infarction or stroke.
- To assess the safety profile of evolocumab in this patient population.
Main Methods:
- An international, double-blind, randomized, placebo-controlled trial involving 12,257 patients with atherosclerosis or diabetes and low-density lipoprotein cholesterol ≥90 mg/dL.
- Patients received either evolocumab (140 mg every 2 weeks) or placebo in a 1:1 ratio.
- Primary endpoints included a composite of coronary heart disease death, myocardial infarction, or ischemic stroke (3-point MACE) and a composite including these plus ischemia-driven revascularization (4-point MACE).
Main Results:
- Evolocumab significantly reduced the risk of 3-point MACE by 25% (HR, 0.75; P<0.001) and 4-point MACE by 19% (HR, 0.81; P<0.001) compared to placebo over a median follow-up of 4.6 years.
- The 5-year Kaplan-Meier estimate for 3-point MACE was 6.2% with evolocumab versus 8.0% with placebo.
- No significant differences in safety event incidence were observed between the evolocumab and placebo groups.
Conclusions:
- PCSK9 inhibition with evolocumab effectively lowers the risk of first cardiovascular events in patients with atherosclerosis or diabetes without a history of myocardial infarction or stroke.
- Evolocumab represents a valuable therapeutic option for primary prevention of cardiovascular events in selected high-risk patients.
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.).
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