- Question
- Does adding icosapent ethyl (EPA) to statin therapy reduce cardiovascular events in patients with chronic coronary artery disease and a low EPA/AA ratio?
- Design
- Prospective, multicenter, randomized, open-label, blinded end-point (PROBE) trial conducted at 95 sites in Japan. A total of 3884 patients were enrolled, of whom 2506 with a low EPA/AA ratio were randomized; median follow-up was 5 years.
- Population
- Patients with stable coronary artery disease on statin treatment and an EPA/arachidonic acid (AA) ratio below 0.4.
- Intervention
- Icosapent ethyl 1800 mg daily on top of statin therapy.
- Control
- Control group without EPA, receiving usual statin therapy.
- Primary outcome
- Composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, unstable angina, and coronary revascularization.
- Results
- The primary end point occurred in 112 of 1225 patients (9.1%) in the EPA group and 155 of 1235 (12.6%) in the control group (HR 0.79; 95% CI 0.62-1.00; P=0.055). The secondary composite of coronary events was lower with EPA (81/1225 [6.6%] vs 120/1235 [9.7%]; HR 0.73; 95% CI 0.55-0.97).
- Safety
- Overall adverse events did not differ between groups, but new-onset atrial fibrillation was more frequent with EPA (3.1% vs 1.6%; P=0.017).
- Conclusion
- Icosapent ethyl produced a numerically lower risk of cardiovascular events that did not reach statistical significance in patients with chronic coronary artery disease, a low EPA/AA ratio, and statin treatment.
- Why it matters
- The trial added evidence on the role of EPA as an add-on to statins in secondary prevention in a population with low EPA levels, although its primary result was inconclusive and it raises caution regarding atrial fibrillation risk.
Card generated automatically with AI from the abstract of the original publication and the trial registry; every figure was checked against those sources. It may contain errors: verify the data at the source before using it for clinical decisions.
Generated on October 14, 2026