Icosapent ethyl for reduction of persistent cardiovascular risk: a critical review of major medical society guidelines and statements

ABSTRACT Introduction REDUCE-IT demonstrated that adding 4 g/day of icosapent ethyl (IPE; purified ethyl ester of eicosapentaenoic acid [EPA]) to statins substantially reduced cardiovascular disease (CVD) events, with few adverse effects. These data prompted numerous leading medical societies across five continents, including the American College of Cardiology, the European Society of Cardiology, and the Japanese Circulation Society, to update their guidelines or scientific/consensus statements to recommend use of IPE for primary and secondary prevention of CVD events. Areas Covered This review discusses the incorporation of IPE into international guidelines and scientific statements, noting areas of consensus and distinction. As background, this review also describes the CVD benefits and risks of IPE as a statin adjunct, and outlines current data regarding the potential mechanisms of CVD risk reduction by EPA (as IPE) beyond triglyceride reduction. Expert Opinion/Commentary IPE is unique among ‘triglyceride-lowering’ treatments in having strong CVD outcomes data and, therefore, a broad international consensus among professional medical society guidelines and statements endorsing its use for CVD risk reduction in patients generally meeting REDUCE-IT inclusion criteria. IPE should be considered for CVD prevention as a statin adjunct in all such patients. Plain Language Summary Cardiovascular disease (CVD) remains the leading cause of death worldwide. Statin monotherapy is conventionally used first-line to reduce the risk of CV events, such as heart attacks and strokes, in patients with elevated cholesterol. However, considerable risk remains despite appropriate control of cholesterol levels with a statin. Consequently, research has focused on treatment of additional therapeutic targets to reduce this remaining CV risk. One such target is elevated blood triglyceride levels. Unfortunately, most drugs that lower triglyceride levels, such as niacin, fibrates, and mixed omega-3 fatty acids, have not reduced the risk of cardiovascular events in clinical trials when added to statin therapy. However, the omega-3 fatty acid eicosapentaenoic acid (‘EPA’) administered in highly purified form as icosapent ethyl (IPE) has emerged as the first omega-3 fatty acid, and the first triglyceride-lowering agent to prevent CV events when added to statins. This was demonstrated most notably in the pivotal REDUCE-IT trial, in which IPE reduced the risk of major CV events by 25% in high-risk patients with mildly to moderately elevated triglyceride levels despite statin-controlled cholesterol levels. The mechanisms responsible for this reduction in CV events appear to go far beyond lowering triglyceride levels alone. In light of the positive results from the REDUCE-IT trial, IPE was approved for CV disease risk reduction globally, including in the United States, Canada, European Union, and the United Kingdom, and its use is being increasingly endorsed in United States and international statements and guidelines for managing CV risk. Despite minor differences among guidelines, there is strong consensus that IPE should be considered for use in CVD prevention in all patients who meet the proposed criteria.