Omega-3 fatty acid therapy for cardiovascular disease: justified or not?

Abstract

To discuss the current evidence regarding the relationship between omega-3 fatty acid intake and atherosclerotic cardiovascular disease (ASCVD) risk. Combined results from randomized controlled trials using low-dosage (≤1.8 g/day of ethyl esters) eicosapentaenoic acid (EPA) or EPA + docosahexaenoic acid (DHA) suggest a small benefit for reducing coronary heart disease risk. The Reduction of Cardiovascular Events with EPA-Intervention Trial (REDUCE-IT) that administered 4 g/day icosapent ethyl (IPE) to individuals on statin at high or very high ASCVD risk with elevated triglycerides demonstrated a 25% relative risk reduction in the composite primary endpoint (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization and unstable angina) for IPE vs. placebo, and a lower hazard for all prespecified individual endpoints other than total mortality. Several national organizations have recommended IPE for ASCVD risk reduction in populations aligning with REDUCE-IT; the Food and Drug Administration has approved IPE for ASCVD risk reduction. However, the Outcomes Study to Assess Statin Residual Risk Reduction with Epanova (EPA + DHA carboxylic acids) in High Cardiovascular Risk Patients with Hypertriglyceridemia was recently stopped for futility. At present, the best available evidence for a role of omega-3 fatty acids in ASCVD risk reduction is for 4 g/day of IPE, as an adjunct to statin therapy, for patients with ASCVD or diabetes mellitus and elevated triglycerides.