The Evolving Role of Omega 3 Fatty Acids in Cardiovascular Disease: Is Icosapent Ethyl the Answer?

Abstract

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality globally. Despite significant advances in pharmacotherapies and the beneficial effects of statin therapy on ASCVD outcomes and progression of atherosclerosis, residual cardiovascular (CV) risk remains. Extensive evidence has identified the contribution of atherogenic dyslipidaemia, which is particularly characterised by elevated triglycerides (TGL) as a key driver of CV risk, even if low-density lipoprotein cholesterol levels are well controlled. Epidemiologic and genetic/Mendelian randomisation studies have demonstrated that elevated TGL levels serve as an independent marker for an increased risk of ischaemic events, highlighting TGLs as a suitable therapeutic target. Clinical studies have shown that omega 3 fatty acids (OM3FA) are effective in lowering TGLs; however, to date, trials and meta-analyses of combined OM3FA products have not demonstrated any clinical CV outcome benefit in patients receiving statins. However, icosapent ethyl (IPE) - a highly purified, stable ethyl ester of eicosapentaenoic acid (EPA) - has been rigorously demonstrated in multiple studies to be a useful adjunctive therapy to address residual CV risk. EPA is an omega-3 polyunsaturated fatty acid that is incorporated into membrane phospholipid bilayers and is reported to exert multiple beneficial effects along the pathway of coronary atherosclerosis. In this brief review, we will provide an overview of the mode of action of IPE in coronary atherosclerosis, the robust clinical evidence and trial data supporting its use, and expert consensus/recommendations on its use in specific populations, as an adjunct to existing anti-atherosclerotic therapies.