Vascepa (Icosapent Ethyl) for Severe Hypertriglyceridemia
Recommended Dosage
For adults with severe hypertriglyceridemia (triglycerides ≥500 mg/dL), icosapent ethyl is dosed at 4 grams per day, taken as either four 0.5-gram capsules twice daily with food or two 1-gram capsules twice daily with food. 1
Patients must swallow capsules whole—do not break open, crush, dissolve, or chew. 1
FDA-Approved Indications
Icosapent ethyl has two distinct FDA-approved indications:
Primary Indication: Severe Hypertriglyceridemia
- As an adjunct to diet to reduce triglyceride levels in adults with severe (≥500 mg/dL) hypertriglyceridemia 1
- The effect on pancreatitis risk has not been determined 1
Cardiovascular Risk Reduction Indication
- As an adjunct to maximally tolerated statin therapy to reduce cardiovascular risk in adults with triglycerides ≥150 mg/dL who have either established cardiovascular disease OR diabetes with ≥2 additional cardiovascular risk factors 1, 2
- This indication is based on the REDUCE-IT trial demonstrating a 25% reduction in major adverse cardiovascular events 3, 4
Pre-Treatment Requirements
Before initiating icosapent ethyl: 1
- Assess baseline lipid levels to confirm triglyceride elevation
- Identify and manage secondary causes including diabetes mellitus, hypothyroidism, or medications that elevate triglycerides
- Ensure patients engage in appropriate nutritional intake and physical activity, which must continue during treatment
Clinical Efficacy
Triglyceride Reduction
In the pivotal MARINE trial for severe hypertriglyceridemia (≥500 mg/dL), icosapent ethyl 4 g/day achieved: 5
- 33.1% placebo-corrected median triglyceride reduction
- No increase in LDL cholesterol (unlike DHA-containing omega-3 products)
- Favorable effects on other lipid parameters
Additional Lipid Effects in High-Risk Patients
In the ANCHOR study (statin-treated patients with triglycerides 200-499 mg/dL and elevated hsCRP ≥2.0 mg/L), icosapent ethyl 4 g/day significantly reduced: 6
- Triglycerides by 20%
- Non-HDL cholesterol by 12.3%
- Apolipoprotein B by 7.4%
- hsCRP by 17.9%
- Without increasing LDL cholesterol
Critical Safety Warnings
Atrial Fibrillation Risk
Icosapent ethyl is associated with increased risk of atrial fibrillation or atrial flutter requiring hospitalization. 1
- In the REDUCE-IT trial, 3% of icosapent ethyl patients versus 2% of placebo patients experienced atrial fibrillation requiring hospitalization for ≥24 hours (HR 1.5,95% CI 1.14-1.98) 1
- Risk is greater in patients with previous history of atrial fibrillation or flutter 1
Fish Allergy Considerations
- Icosapent ethyl contains ethyl esters of EPA obtained from fish oil 1
- Contraindicated in patients with known hypersensitivity to icosapent ethyl or any components 1
- Unknown whether patients with fish/shellfish allergies have increased allergic reaction risk 1
Common Adverse Events
The most common adverse events are gastrointestinal in nature, with a tolerability profile similar to placebo. 5, 7
Position in Treatment Algorithm
For Severe Hypertriglyceridemia (≥500 mg/dL)
Fibrates (fenofibrate) remain first-line therapy to prevent acute pancreatitis, providing 30-50% triglyceride reduction. 3 Icosapent ethyl can be added as adjunctive therapy after triglycerides are reduced below 500 mg/dL. 3
For Moderate Hypertriglyceridemia with Cardiovascular Risk
Icosapent ethyl 2 g twice daily is the evidence-based choice for patients on maximally tolerated statin therapy with controlled LDL cholesterol but persistent triglycerides 135-499 mg/dL who have established cardiovascular disease or diabetes with ≥2 additional risk factors. 8, 9, 3
This represents the only triglyceride-lowering therapy with proven cardiovascular outcomes benefit (25% relative risk reduction in major adverse cardiovascular events, NNT=21). 3, 4
Key Advantages Over Other Omega-3 Products
- High-purity EPA (≥96%) without DHA, avoiding DHA-associated LDL cholesterol increases 5, 4
- Only omega-3 product FDA-approved for cardiovascular risk reduction 9
- No drug-drug interactions with statins or fibrates 7
- Does not require pancreatic lipase for absorption (unlike ethyl ester formulations) 7