What is Vascepa (icosapent ethyl)?

Vascepa (Icosapent Ethyl): A Cardiovascular Risk Reduction Medication

Vascepa (icosapent ethyl) is a highly purified ethyl ester of eicosapentaenoic acid (EPA) that significantly reduces cardiovascular events in high-risk patients with elevated triglycerides, while also serving as an effective treatment for severe hypertriglyceridemia. 1, 2

Composition and Mechanism

• Vascepa contains ≥96% EPA ethyl ester without docosahexaenoic acid (DHA) 2, 3
• Each capsule contains 1 gram of icosapent ethyl in a soft gelatin capsule 2
• Mechanism of action includes:
  • Reduction of hepatic very low-density lipoprotein triglycerides (VLDL-TG) synthesis
  • Enhancement of triglyceride clearance from circulating VLDL particles
  • Increased β-oxidation and decreased hepatic lipogenesis 2
  • Anti-inflammatory effects (39.9% reduction in hs-CRP) 4
  • Possible anti-arrhythmic or membrane stabilizing effects 4, 1

FDA-Approved Indications

1. Severe hypertriglyceridemia: As an adjunct to diet in adults with triglyceride levels ≥500 mg/dL 2, 3
2. Cardiovascular risk reduction: In patients with established cardiovascular disease or diabetes plus additional risk factors who have elevated triglycerides (135-499 mg/dL) and controlled LDL-C on statin therapy 1

Clinical Efficacy

• REDUCE-IT trial: Demonstrated a 25% relative risk reduction in cardiovascular events 4, 1

  • 26% reduction in the composite of cardiovascular death, nonfatal MI, or nonfatal stroke 1
  • 20% reduction in cardiovascular death 1
  • Significant reductions in cardiac arrest and sudden cardiac death 4, 1
  • Number needed to treat of only 21 patients over the study period 4

• Triglyceride reduction: Lowers triglycerides by approximately 20-33% compared to placebo 1, 3

• Unique benefit: Unlike other omega-3 products containing both EPA and DHA, Vascepa does not increase LDL-C levels 1, 3

Dosage and Administration

• Recommended dose: 2 grams twice daily with food (total daily dose of 4 g) 1
• Should be taken with or following meals 2
• Maximum effects on lipid levels typically occur after 4-12 weeks of treatment 1

Safety Profile and Adverse Effects

• Generally well-tolerated with a safety profile similar to placebo 4, 3
• Notable adverse effects include:
  • Increased risk of atrial fibrillation (5.3% vs. 3.9% with placebo) 4, 1
  • Atrial fibrillation requiring hospitalization (3.1% vs. 2.1%) 4
  • Peripheral edema (6.5% vs. 5.0%) 4, 1
  • Constipation (5.4% vs. 3.6%) 4, 1
  • Trend toward more bleeding-related disorders, especially in patients on anticoagulants 4, 1

Monitoring Recommendations

• Monitor for atrial fibrillation symptoms 1
• Monitor for bleeding events, especially in patients taking anticoagulants or antiplatelet therapies 1
• Monitor lipid levels to assess treatment efficacy 1
• In patients with hepatic impairment, monitor ALT and AST levels periodically 2

Special Populations

• Elderly: No overall differences in safety or effectiveness observed in patients ≥65 years 2
• Pregnancy: No adequate human data; animal studies showed possible developmental effects at high doses 2
• Lactation: Omega-3 fatty acids are detected in human milk; benefits of breastfeeding should be considered against potential risks 2
• Pediatric use: Safety and effectiveness not established 2
• Patients with prior PCI: Particularly beneficial with a 34% reduction in primary composite endpoint and number needed to treat of only 12 5

Clinical Pearls

• Vascepa is distinct from other omega-3 products that contain both EPA and DHA
• The cardiovascular benefits appear to extend beyond simple triglyceride reduction
• Combination omega-3 products containing both EPA and DHA are not indicated for cardiovascular risk reduction 6
• Patients should be on moderate- or high-intensity statin therapy to be considered for icosapent ethyl for cardiovascular risk reduction 1