Evolocumab lowers first major cardiovascular events
In high-risk adults without prior heart attack or stroke, evolocumab reduced first major cardiovascular events without new safety concerns.
*Randomized, double-blind, placebo-controlled trial; Level 1b (OCEBM).

Citation

Bohula EA, Marston NA, Bhatia AK, et al.; VESALIUS-CV Investigators. Evolocumab in Patients without a Previous Myocardial Infarction or Stroke. N Engl J Med. 2026;394:117-127. doi:10.1056/NEJMoa2514428.

Background

Evolocumab is known to reduce cardiovascular events in people who already had a heart attack or stroke. This trial tested whether it can prevent a first major event in high-risk patients.

Patients

12,257 adults with atherosclerosis or diabetes, no prior heart attack or stroke, and low-density lipoprotein cholesterol ≥90 mg/dL on stable lipid-lowering therapy.

Intervention

Evolocumab 140 mg injection every 2 weeks.

Control

Matching placebo injections.

Outcome

Two primary composite outcomes: (1) coronary heart disease death, heart attack, or ischemic stroke; (2) the same plus ischemia-driven arterial revascularization.

Follow-up Period

Median 4.6 years (5-year event estimates reported).

Results

Outcome Evolocumab (5-year risk) Placebo (5-year risk) Relative effect Absolute risk reduction NNT (5 years)
Coronary heart disease death, heart attack, or ischemic stroke (primary) 6.2% 8.0% Hazard ratio 0.75 (95% CI, 0.65 to 0.86) 1.8% 56
Primary outcome plus ischemia-driven revascularization (primary) 13.4% 16.2% Hazard ratio 0.81 (95% CI, 0.73 to 0.89) 2.8% 36
Heart attack 2.7% 4.1% Hazard ratio 0.64 (95% CI, 0.52 to 0.79) 1.4% 72
Ischemia-driven arterial revascularization 10.1% 12.5% Hazard ratio 0.79 (95% CI, 0.70 to 0.88) 2.4% 42
Primary analyses were intention-to-treat. No between-group difference was seen in serious adverse events or discontinuation due to adverse events.

Limitations

Mostly White participants; some outcomes exploratory due to testing sequence; injection therapy may limit uptake.

Funding

Amgen funded; sponsor supplied drug and collected data.

Clinical Application

For high-risk patients without prior heart attack or stroke and persistently high cholesterol despite therapy, consider evolocumab to prevent first major events.