Results from a Phase 3 trial (NCT03872401) evaluating evolocumab (Repatha) in patients at high cardiovascular risk without prior myocardial infarction or stroke were posted on 2026-06-25. The study demonstrated that evolocumab significantly reduced the risk of major cardiovascular events, such as coronary heart disease (CHD) death, myocardial infarction (MI), or ischemic stroke, with a hazard ratio of 0.75 (p=0.001) compared to placebo.
Background
The trial investigated the effect of evolocumab in adults at high risk of a cardiovascular event, specifically those with Coronary Heart Disease (CHD) but without a prior myocardial infarction or stroke. The study aimed to assess the impact of lowering low-density lipoprotein cholesterol (LDL-C) with evolocumab on major cardiovascular events.
Trial design
This was a Phase 3 trial (NCT03872401) titled "Effect of Evolocumab in Patients at High Cardiovascular Risk Without Prior Myocardial Infarction or Stroke". The study enrolled 12,301 participants with Coronary Heart Disease (CHD). The trial's purpose was to assess the effect of evolocumab on major cardiovascular events. Interventions included evolocumab 140 mg Q2W and placebo Q2W.
Key results
The trial reported key measurements and analyses comparing evolocumab 140 mg Q2W to placebo Q2W:
- For the outcome of Coronary Heart Disease (CHD) Death, Myocardial Infarction (MI), or Ischemic Stroke, Whichever Occurred First, 336 participants in the evolocumab group experienced an event compared to 443 participants in the placebo group. The hazard ratio was 0.75 (95.0% CI: 0.65, 0.86; p=0.001).
- For the outcome of CHD Death, MI, Ischemic Stroke, or Any Ischemia-driven Arterial Revascularization, Whichever Occurred First, 747 participants in the evolocumab group experienced an event compared to 907 participants in the placebo group. The hazard ratio was 0.81 (95.0% CI: 0.73, 0.89; p=0.001).
- For the outcome of MI, Ischemic Stroke, or Any Ischemia-driven Arterial Revascularization, 674 participants in the evolocumab group experienced an event compared to 834 participants in the placebo group. The hazard ratio was 0.79 (95.0% CI: 0.72, 0.88; p=0.001).
- For the outcome of CHD Death, MI, or Any Ischemia-driven Arterial Revascularization, 664 participants in the evolocumab group experienced an event compared to 819 participants in the placebo group. The hazard ratio was 0.79 (95.0% CI: 0.72, 0.88; p=0.001).
- For the outcome of Cardiovascular Death, MI, or Ischemic Stroke, 374 participants in the evolocumab group experienced an event compared to 503 participants in the placebo group. The hazard ratio was 0.73 (95.0% CI: 0.64, 0.84; p=0.001).
- For the outcome of CHD Death or MI, 232 participants in the evolocumab group experienced an event compared to 313 participants in the placebo group. The hazard ratio was 0.73 (95.0% CI: 0.62, 0.87; p=0.001).
What this means
The posted trial results indicate that evolocumab consistently demonstrated a statistically significant reduction in various composite cardiovascular endpoints in high-risk patients with Coronary Heart Disease who had not previously experienced a myocardial infarction or stroke. The observed hazard ratios, all below 0.82 and with a p-value of 0.001 across all measured outcomes, suggest a substantial benefit in preventing major cardiovascular events for this specific patient population.
Source
The trial results were posted on 2026-06-25 on ClinicalTrials.gov, an official database of clinical studies. The full details are available on clinicaltrials.gov under the identifier NCT03872401.