Indications and Usage of Icosapent Ethyl for Hypertriglyceridemia
Icosapent ethyl is indicated as an adjunct to diet to reduce triglyceride levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia, and in patients with established atherosclerotic cardiovascular disease or diabetes with additional cardiovascular risk factors who have triglycerides 135-499 mg/dL despite statin therapy. 1, 2
Primary Indications
- Icosapent ethyl (4g/day, taken as 2g twice daily with food) is FDA-approved for severe hypertriglyceridemia (≥500 mg/dL) to reduce triglyceride levels 1
- In patients with atherosclerotic cardiovascular disease (ASCVD) or diabetes with additional cardiovascular risk factors who are on statin therapy with controlled LDL-C but elevated triglycerides (135-499 mg/dL), icosapent ethyl can be added to reduce cardiovascular risk 2
- For patients with ischemic stroke or TIA with fasting triglycerides 135-499 mg/dL and LDL-C of 41-100 mg/dL on moderate or high-intensity statin therapy, icosapent ethyl 2g twice daily is reasonable to reduce risk of recurrent stroke 2
Clinical Evidence Supporting Usage
The REDUCE-IT trial demonstrated that in patients with established cardiovascular disease or diabetes plus other risk factors, with triglycerides 135-499 mg/dL (median 216 mg/dL) on statin therapy, icosapent ethyl 4g/day reduced: 2
- Primary composite endpoint (cardiovascular death, nonfatal MI, nonfatal stroke, coronary revascularization, or unstable angina) by 25% (p<0.001)
- Cardiovascular death, nonfatal MI, or nonfatal stroke by 26% (p<0.001)
- Cardiovascular death specifically by 20% (p=0.03)
The cardiovascular benefit appears to be independent of the triglyceride-lowering effect, distinguishing icosapent ethyl from other triglyceride-lowering therapies 2
Patient Selection Criteria
For severe hypertriglyceridemia (≥500 mg/dL): all adult patients are eligible for treatment to reduce triglyceride levels and risk of pancreatitis 1, 2
For moderate hypertriglyceridemia (135-499 mg/dL): patients must have: 2
- Established ASCVD or diabetes with additional cardiovascular risk factors
- Be on statin therapy with controlled LDL-C (41-100 mg/dL)
- HbA1c <10% (for optimal benefit)
- No history of pancreatitis, atrial fibrillation, or severe heart failure
Dosing and Administration
The recommended daily dose is 4 grams per day taken as: 1
- Two 1-gram capsules twice daily with food, OR
- Four 0.5-gram capsules twice daily with food
Capsules should be swallowed whole and not broken, crushed, dissolved, or chewed 1
Prior to initiation: 1
- Assess lipid levels
- Identify and manage other causes of hypertriglyceridemia (diabetes, hypothyroidism, medications)
- Implement appropriate dietary and lifestyle modifications
Important Distinctions from Other Omega-3 Products
Icosapent ethyl contains ≥96% pure eicosapentaenoic acid (EPA) ethyl ester and does not contain docosahexaenoic acid (DHA) 3
Unlike products containing both EPA and DHA, icosapent ethyl does not increase LDL-C levels 3, 4
The cardiovascular benefits demonstrated in the REDUCE-IT trial should not be extrapolated to other omega-3 fatty acid products 2
Safety Considerations and Monitoring
Increased risk of atrial fibrillation or atrial flutter requiring hospitalization (3% vs 2% with placebo) 1
Higher risk in patients with previous history of atrial fibrillation or flutter 1
Potential for allergic reactions in patients with fish allergies (contains EPA derived from fish oil) 1
Monitor lipid parameters 4-12 weeks after initiation to assess efficacy and adherence 2
Contraindications
Known hypersensitivity to icosapent ethyl or any of its components 1
The combination of statin plus fibrate has not shown improved cardiovascular outcomes and is generally not recommended 2
Similarly, statin plus niacin combination therapy has not demonstrated additional cardiovascular benefit beyond statin therapy alone and may increase stroke risk 2
By following these guidelines, clinicians can appropriately prescribe icosapent ethyl to reduce cardiovascular risk in patients with hypertriglyceridemia while minimizing potential adverse effects.