In the European Union, icosapent ethyl is indicated to reduce cardiovascular risk as an adjunct to statin therapy.
In the United States, icosapent ethyl is indicated as an adjunct to maximally tolerated statin therapy to reduce the risk of myocardial infarction, stroke, coronary revascularization, and unstable angina requiring hospitalization in adults with elevated triglyceride levels (≥ 150 mg/dL) and established cardiovascular disease or diabetes and two or more additional risk factors for cardiovascular disease. It is also indicated as an adjunct to diet to reduce triglyceride levels in adults with severe (≥ 500 mg/dL) hypertriglyceridemia.
Intake of large doses (2.0 to 4.0 g/day) of long-chain omega-3 fatty acids as prescription drugs or dietary supplements are generally required to achieve significant (> 15%) lowering of triglycerides, and at those doses the effects can be significant (from 20% to 35% and even up to 45% in individuals with levels greater that 500 mg/dL). It appears that both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) lower triglycerides; however, DHA alone appears to raise low-density lipoprotein (the variant which drives atherosclerosis; sometimes  called "bad cholesterol") and LDL-C values (most typically only a calculated estimate and not measured by labs from person's blood sample for technical and cost reasons; however, this is accurately calculated with a less common NMR lipid panel lab), whilst eicosapentaenoic acid (EPA) alone does not and instead lowers the parameters aforementioned.