What is the use of icosapent ethyl (EPA ethyl ester)?

From the Guidelines

Icosapent ethyl should be considered for patients with established cardiovascular disease or diabetes plus other risk factors who have triglyceride levels of 150 mg/dL or higher despite being on maximally tolerated statin therapy, as it has been shown to reduce cardiovascular risk by 25% 1.

Key Points

• The standard dose of icosapent ethyl is 2 grams (two 1-gram capsules) taken twice daily with food, for a total daily dose of 4 grams.
• Icosapent ethyl works by reducing inflammation, improving endothelial function, and stabilizing atherosclerotic plaques.
• Unlike some other omega-3 supplements, it contains only purified eicosapentaenoic acid (EPA) without docosahexaenoic acid (DHA), which may explain its superior cardiovascular benefits.
• Common side effects include joint pain, swelling, and potential increased risk of bleeding, so patients on anticoagulants should be monitored carefully.

Recommendations

• Icosapent ethyl should be taken consistently long-term as part of a comprehensive cardiovascular risk reduction plan that includes lifestyle modifications and other appropriate medications.
• Hypertriglyceridemia should be addressed with nutritional and lifestyle changes, including weight loss and abstinence from alcohol.
• Severe hypertriglyceridemia (fasting triglycerides ≥500 mg/dL and especially >1,000 mg/dL) may warrant pharmacologic therapy (fibrin acid derivatives and/or fish oil) and reduction in dietary fat to reduce the risk of acute pancreatitis.

Evidence

• The Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE-IT) demonstrated a 25% relative risk reduction for the primary end point composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina 1.
• The 2025 guidelines recommend considering the addition of icosapent ethyl to reduce cardiovascular risk in individuals with ASCVD or other cardiovascular risk factors on a statin with managed LDL cholesterol but elevated triglycerides (150–499 mg/dL) 1.

From the FDA Drug Label

INDICATIONS AND USAGE Icosapent ethyl capsules are an ethyl ester of eicosapentaenoic acid (EPA) indicated: as an adjunct to diet to reduce TG levels in adultpatients with severe (≥ 500 mg/dL) hypertriglyceridemia. The main use of icosapent ethyl is to reduce triglyceride (TG) levels in adults with severe hypertriglyceridemia (≥ 500 mg/dL) as an adjunct to diet 2. Key points about icosapent ethyl include:

• It is an ethyl ester of eicosapentaenoic acid (EPA)
• The daily dose is 4 grams per day
• It is contraindicated in patients with known hypersensitivity to icosapent ethyl or any of its components 2.

From the Research

Icosapent Ethyl Overview

• Icosapent ethyl is a highly purified ethyl ester of eicosapentaenoic acid (EPA) that safely and effectively reduces cardiovascular events in adults with elevated triglycerides 3.
• It is prescribed at a dose of 2 grams twice daily and is indicated in patients at high cardiovascular risk who have fasting or non-fasting triglyceride levels ≥150 mg/dl despite maximally tolerated statin treatment, or in individuals with triglyceride levels ≥500 mg/dl 3.

Mechanism of Action and Efficacy

• Icosapent ethyl lowers triglyceride levels without increasing low-density lipoprotein cholesterol (LDL-C) levels 4, 5.
• It has been shown to reduce the risk of ischemic events, including cardiovascular death, in patients with elevated triglyceride levels despite the use of statins 6.
• The Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) demonstrated that icosapent ethyl significantly lowered the risk of cardiovascular events in patients with established cardiovascular disease or with diabetes and other risk factors 6.

Safety and Tolerability

• Icosapent ethyl has a tolerability profile similar to that of placebo, with no significant increase in adverse effects such as flushing, hepatotoxicity, myopathy, or elevated glucose levels 4, 5.
• However, a larger percentage of patients in the icosapent ethyl group were hospitalized for atrial fibrillation or flutter compared to the placebo group 6.

Clinical Use and Recommendations

• Icosapent ethyl is approved by the US FDA as an adjunct to a maximally tolerated statin to reduce the risk of cardiovascular events in adults with serum triglycerides > 150 mg/dl and have either established cardiovascular disease or diabetes and two or more additional cardiovascular risk factors 7.
• It is recommended for use in patients with severe hypertriglyceridemia (≥500 mg/dl) or in those with elevated triglyceride levels despite statin therapy 3, 4, 5.