Rationale and Design of the RESPECT-EPA Trial

The RESPECT-EPA trial design paper described a multicenter Japanese RCT randomizing 2,460 patients with stable coronary artery disease and dyslipidemia to icosapentaenoic acid (EPA, 1800 mg/day) on top of statin therapy versus statin alone, with cardiovascular events as the primary endpoint.

The trial was designed as a definitive Japanese trial of EPA in secondary prevention, building on the earlier JELIS trial (which showed benefit for EPA 1800 mg/day in a Japanese population with lower statin intensity) and attempting to address its limitations in a higher-statin background context. Results were pending at publication.

The RESPECT-EPA design is relevant to the ongoing controversy about omega-3 cardiology. JELIS showed benefit; REDUCE-IT showed benefit with EPA 4 g/day in Western populations; STRENGTH showed no benefit with EPA+DHA. A positive Japanese EPA trial at 1800 mg/day would narrow the question to EPA dose and formulation versus population-specific factors (baseline EPA levels are higher in Japan due to dietary fish intake, potentially limiting additional benefit from supplementation).

We rate the evidence limited — a design paper reporting rationale, not results. Clinical significance reflects the importance of the trial if positive.