Effects of purified EPA on CV events in patients with CAD on statin therapy
RESPECT-EPA – Randomized Trial for Evaluating Secondary Prevention Efficacy of Combination Therapy - Statin and Eicosapentaenoic Acid
Presented at the AHA Scientific Sessions 2022 by: Hiroyuki Daida, MD, PhD - Tokyo, Japan
Introduction and methods
The JELIS study demonstrated in 2005 that highly purified eicosapentaenoic acid (EPA) had a beneficial effect on CV outcomes in patients with and without CAD. The current RESPECT-EPA study (Randomized trial for Evaluating the Secondary Prevention Efficacy of Combination Therapy – statin and EPA) now aimed to evaluate the effects of EPA in combination with statin therapy on CV events in Japanese patients with chronic CAD.
Eligible patients for the open-label RCT were 20-79 years old, had chronic CAD, were taking statins for at least 1 month before inclusion, and had an EPA/arachidonic acid (AA) ratio <0.4 at enrollment. A total of 2506 patients were randomized 1:1 to receive EPA (icosapent ethyl 1,800 mg/day) plus statin or statin alone. The enrollment period was 4 years and follow-up period was 4 years from the end of the enrollment period. The primary endpoint of the RCT was a composite of CV death, nonfatal MI, nonfatal cerebral infarction, unstable angina pectoris, or revascularization. The secondary endpoints included composite events of CAD, composite events of stroke and events related to death.
- The primary endpoint occurred in 10.9% of patients in the purified EPA group and in 14,9% of patients in the control group, resulting in an HR of 0.785 (95% CI 0.616-1.001, P=0.0547).
- Purified EPA significantly reduced the composite secondary endpoint of sudden cardiac death, MI, unstable angina, or coronary revascularization (8.0% vs. 11.3%, HR 0.734, 95% CI 0.554-0.973, P=0.0306).
- There were no differences in all-cause mortality and CV mortality between treatment groups.
- There were also no significant differences between groups for separate secondary endpoints (MI, ischemic stroke, hemorrhagic stroke, coronary revascularization, and unstable angina requiring emergency hospitalization).
- Safety results showed a significant increase in gastrointestinal disorders (3.4% vs 1.2%, P<0.001) and new-onset atrial fibrillation (3.1% vs. 1.6%, P=0.017) in the purified EPA group compared with the control group.
- Additionally, a post-hoc analysis was performed which excluded patients with an EPA increase from baseline of >30 µg/mL in the control group, and of <30 µg/mL in the purified EPA group. The HR for the primary endpoint in this post-hoc analysis was 0.725 (95% CI 0.553-0.951, P=0.0202).
The open-label RCT of RESPECT-EPA showed a non-significant reduction in the primary endpoint with purified EPA in patients with chronic CAD on statin therapy. Purified EPA did significantly reduce the composite secondary endpoint of sudden cardiac death, MI, unstable angina, or coronary revascularization. Safety results showed that use of purified EPA was associated with a significant increase in gastrointestinal disorders and new-onset atrial fibrillation.
-Our reporting is based on the information provided at the AHA Scientific Sessions-