Icosapent ethyl (IPE) treatment may be associated with a numerically lower risk of cardiovascular events, but this reduction did not reach statistical significance in patients with chronic coronary artery disease (CAD) and a low ratio of eicosapentaenoic acid to arachidonic acid (EPA/AA) on statin treatment, according to the results of the RESPECT-EPA study published in Circulation.

The prospective, multicenter, open-label, blinded endpoint study, conducted at 95 sites across Japan, randomly assigned 2,506 patients (82.7% men, 42% ≥70 years old) with stable CAD, a low EPA/AA ratio (<0.4) and at least one month of stable statin treatment to either an EPA treatment of 1,800 mg/d of IPE or control; statins were prescribed according to Japanese guideline recommendations. The median EPA/AA ratio of the 1,249 patients in the treatment group was 0.243 vs. 0.235 in the 1,257 patients in the control group.

Results showed that over the median five-year follow-up, the primary endpoint, a composite of cardiovascular death, nonfatal myocardial infarction (MI), nonfatal ischemic stroke, unstable angina and coronary revascularization, occurred in 9.1% (112) of patients in the treatment group and 12.6% (155) of patients in the control group (hazard ratio [HR], 0.79; 95% CI, 0.62-1.00; p=0.055).

However, the composite secondary endpoint, consisting of sudden cardiac death, fatal and nonfatal MI, unstable angina requiring emergency hospitalization plus coronary revascularization or coronary revascularization itself, was significantly lower in the treatment group vs. the control group: 6.6% (81 patients) vs. 9.7% (120 patients) (HR, 0.73; 95% CI, 0.55-0.97). Adverse events did not differ between the two groups, but authors Katsumi Miyauchi, MD, et al., note that the rate of new-onset atrial fibrillation was significantly higher in the treatment group (3.1% vs. 1.6% in the control group; p=0.017).

While IPE treatment lowered the rate of the first occurrence of a primary outcome, it significantly reducing the secondary endpoint, note the authors, and the patients who responded to IPE had notably fewer events than in the control group. "These findings collectively imply that IPE could hold clinical significance in mitigating future events," in this population, they write, but "any potential benefit of [IPE] would be in the context of a statistically significantly increased risk of atrial fibrillation."

Clinical Topics: Arrhythmias and Clinical EP, Dyslipidemia, Atherosclerotic Disease (CAD/PAD), Atrial Fibrillation/Supraventricular Arrhythmias, Lipid Metabolism, Nonstatins

Keywords: Eicosapentaenoic Acid, Arachidonic Acid, Coronary Artery Disease, Atrial Fibrillation