What is the difference between Icosapent ethyl (Eicosapentaenoic acid) and Omega-3 ethyl esters in the treatment of hypertriglyceridemia?

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Last updated: June 13, 2025View editorial policy

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From the Guidelines

Icosapent ethyl is the preferred treatment for hypertriglyceridemia due to its superior cardiovascular risk reduction and purified eicosapentaenoic acid (EPA) composition, as demonstrated in the REDUCE-IT trial 1. The main difference between icosapent ethyl and omega-3 ethyl esters is their composition, with icosapent ethyl containing only purified EPA and omega-3 ethyl esters containing both EPA and docosahexaenoic acid (DHA). This distinction is crucial, as icosapent ethyl has shown superior cardiovascular risk reduction in patients with elevated triglycerides.

Key differences between icosapent ethyl and omega-3 ethyl esters:

  • Composition: Icosapent ethyl contains only purified EPA, while omega-3 ethyl esters contain both EPA and DHA.
  • Dosage: The typical dosage for icosapent ethyl is 2 grams twice daily with food, whereas omega-3 ethyl esters are usually prescribed as 4 grams daily.
  • Cardiovascular risk reduction: Icosapent ethyl has demonstrated superior cardiovascular risk reduction in patients with elevated triglycerides, as shown in the REDUCE-IT trial 1.
  • Side effects: Both medications can cause side effects, including arthralgia, gastrointestinal disturbances, and potential bleeding risk, but icosapent ethyl has a more favorable side effect profile.

Clinical implications:

  • Icosapent ethyl is indicated for patients with elevated triglyceride levels (≥150 mg/dL) and established cardiovascular disease or diabetes plus at least one other cardiovascular risk factor 1.
  • Omega-3 ethyl esters are indicated only as an adjunct to diet to reduce triglyceride levels in adult patients with severe hypertriglyceridemia (triglycerides ≥500 mg/dL) 1.
  • The REDUCE-IT trial demonstrated that icosapent ethyl significantly reduced cardiovascular events in high-risk patients with elevated triglycerides who were already on statin therapy 1.
  • Recent studies have confirmed that omega-3 fatty acids, including icosapent ethyl, increase the risk of atrial fibrillation (AF) 1.

From the Research

Difference between Icosapent Ethyl and Omega-3 Ethyl Esters

  • Icosapent ethyl is a high-purity prescription form of eicosapentaenoic acid (EPA) ethyl ester, whereas omega-3 ethyl esters contain a mixture of EPA and docosahexaenoic acid (DHA) 2.
  • Icosapent ethyl has been shown to lower triglyceride levels without raising low-density lipoprotein cholesterol (LDL-C) levels, whereas omega-3 ethyl esters may raise LDL-C levels due to the presence of DHA 2, 3.
  • Studies have demonstrated that switching from omega-3-acid ethyl esters to icosapent ethyl can result in beneficial changes in lipid profiles, including reductions in triglyceride and LDL-C levels 3, 4.

Mechanism of Action

  • Icosapent ethyl increases plasma and red blood cell levels of EPA, which corresponds to its triglyceride-lowering effect 5.
  • The increase in EPA levels with icosapent ethyl also decreases the arachidonic acid/EPA plasma ratio, which may contribute to its cardiovascular benefits 5.

Clinical Implications

  • Icosapent ethyl has been approved by the FDA for the treatment of hypertriglyceridemia and has been shown to reduce cardiovascular event risk in high-risk patients 6.
  • Omega-3 ethyl esters, on the other hand, are available as dietary supplements and have limited or no evidence for cardiovascular event risk reduction 2, 6.
  • The choice between icosapent ethyl and omega-3 ethyl esters should be based on individual patient needs and medical history, with consideration of the potential benefits and risks of each treatment option 2, 3, 4.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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