EPA Reaches Borderline Statistical Significance in RESPECT-EPA Trial

Highly purified eicosapentaenoic acid (EPA) reduced the risk of adverse cardiovascular events in patients with chronic coronary artery disease (CAD) with borderline statistical significance.

Meanwhile, highly purified EPA of 1,800 mg/day was significantly associated with a decreased risk of the composite of coronary events included in the secondary outcomes of the Randomized Trial for Evaluating the Secondary Prevention Efficacy of Combination Therapy (RESPECT-EPA).

“Present findings indicate a possible prognostic benefit of EPA at 1,800 mg/day in chronic CAD patients with statins whose EPA/arachidonic acid (AA) ratio was low at < 0.4,” said study author Hiroyuki Daida, MD, PhD, Juntendo University School of Medicine.

The late-breaking findings were presented at the American Heart Association Scientific Sessions 2022 in Chicago.

Previously, in 2005, the Japan EPA Lipid Intervention Study (JELIS) demonstrated a beneficial effect of highly purified EPA on cardiovascular outcomes in patients with and without CAD. Now, optimal medical therapy with high-intensity statins has become the gold standard of care for CAD patients, but there is a substantial residual risk.

Investigators noted the conflicting results in recent omega-3 fatty acid trials have created controversy over the relevance of EPA intervention alongside the latest optimal medical therapy. The clinical implications of serum EPA/arachidonic acid ratio as a biomarker has not been validated.

The RESPECT-EPA aimed to evaluate the effect of EPA on cardiovascular events in combination with statins and additionally addressed a prognostic implication of EPA/AA ratio for patients with CAD. Patients were required to receive statins for at least one month prior to inclusion and were 20 - 79 years old at the time of providing consent for the study.

The trial consisted of two parts, with an open-label randomized controlled trial (RCT) and biomarker study part (prospective cohort study design). The RCT included patients with low EPA/AA (lower than 0.4) and the patients were then randomized to highly purified EPA (icosapent ethyl; 1800 mg/day) or control.

Individuals in the high EPA/AA ratio (greater than or equal to 0.4) and the control group in the RCT part were included in the biomarker study to assess the usefulness of EPA/AA ratio as a biomarker for cardiovascular events prediction.

The study’s primary endpoints were a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal cerebral infarction, unstable angina pectoris, and clinically indicated coronary revascularization. Secondary endpoints included composite events of CAD, composite events of stroke, and events related to death.

In the RCT, a total of 1225 patients were allocated to the EPA group and 1235 patients to the control group. Baseline characteristics were similar between the EPA and control groups and the baseline median EPA/AA ratio was 0.243 and 0.235, respectively.

For the biomarker study, a total of 1314 patients with high EPA/AA ratio were registered and their baseline median EPA/AA ratio was 0.577. It consisted of a median follow-up period was 5 years.

Within the RCT, the primary outcome occurred in 112 in the EPA group and 155 in the control group (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.62 - 1.00; stratified log-rank P-value = .055). Meanwhile, the secondary endpoint of coronary events occurred in 81 patients in the EPA group and 120 in the control group (HR, 0.73; 95% CI, 0.55 - 0.97; stratified log-rank P-value = .03).

The HR for all-cause mortality was 0.682 (95% CI, 0.385 - 1.208; stratified log-rank P-value = .1928) and the HR for cardiovascular mortality was 0.888 (95% CI, 0.625 - 1.262; stratified log-rank P-value = .5303).

Investigators reported a significantly higher incidence of new onset atrial fibrillation in the EPA group compared to the control group.

“Randomized Trial for Evaluating Secondary Prevention Efficacy of Combination Therapy -Statin and Eicosapentaenoic Acid,” was presented at AHA 2022.