[Icosapent ethyl for the reduction of residual cardiovascular risk]

Despite the effectiveness of statins in reducing cardiovascular events and slowing the progression of coronary atherosclerosis, significant residual cardiovascular risk persists. In the REDUCE-IT trial, icosapent ethyl (IPE), a highly purified ethyl ester of eicosapentaenoic acid (EPA), has been demonstrated to significantly lower the risk of primary and secondary composite endpoints, including major adverse cardiovascular events and cardiovascular death, when added to a statin compared to placebo. This clinical benefit may partially result from IPE's moderate triglyceride-lowering properties; however, it also significantly reduces levels of atherogenic remnant particle-cholesterol. Previous trials using mixed formulations of omega-3 fatty acids (EPA/docosahexaenoic acid [DHA]) or low-dose IPE have not demonstrated similar benefits, despite achieving comparable triglyceride reductions. These discrepancies have prompted investigations into the mechanistic differences between omega-3 fatty acids, as EPA and DHA exhibit distinct membrane interactions, metabolic products, tissue distributions, and biological effects. Moreover, IPE exerts several beneficial actions on atherosclerosis beyond its triglyceride-lowering properties, improving endothelial function, reducing intra-plaque inflammation and oxidative stress, exhibiting antithrombotic properties, and improving insulin sensitivity. IPE is scientifically plausible as a potential antiatherosclerotic agent based on mechanistic, pathophysiological, outcomes, and plaque-imaging studies. This review aims to synthesize the current evidence regarding IPE and examine its potential applications in light of the European Society of Cardiology guideline recommendations and existing national regulations.