Omega-3 Fatty Acids in the Management of Cardiovascular Disease Prevention

Abstract Purpose Omega-3 polyunsaturated fatty acids lower triglycerides and modulate inflammation, thrombosis, and endothelial function, providing a rationale for their use in cardiovascular prevention. This review examines the influence of formulation, dose, and patient selection on clinical outcomes. Methods A targeted PubMed search through 31 May 2026 informed the selection of randomized trials and relevant mechanistic and observational studies, complemented by guideline and regulatory documents and selected publications added during revision. Results Low-dose mixed eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) formulations were generally neutral in contemporary prevention trials. JELIS reported fewer major coronary events with EPA 1.8 g/day (2.8% vs. 3.5%; hazard ratio 0.81). In REDUCE-IT, icosapent ethyl 4 g/day reduced major ischemic events (17.2% vs. 22.0%; hazard ratio 0.75), whereas STRENGTH found no benefit with 4 g/day EPA/DHA (12.0% vs. 12.2%; hazard ratio 0.99). Differences in biological exposure, placebo choice, and pharmacological properties may contribute to these findings, although their relative importance remains debated. Evidence for stroke, heart failure, and peripheral artery disease varies by population and endpoint, while higher-dose therapy requires attention to atrial fibrillation and bleeding. Conclusion Current evidence supports prescription icosapent ethyl in selected statin-treated patients with persistent hypertriglyceridemia, with treatment guided by cardiovascular risk, formulation, and dose rather than considering omega-3 preparations as an interchangeable class.