Vascepa (icosapent ethyl) was first approved in 2012 for severe hypertriglyceridemia (≥500 mg/dL) as an adjunct therapy to diet to reduce triglyceride (TG) levels. In 2019, the approval has been expanded by the Food and Drug Administration (FDA) to use Vascepa (icosapent ethyl) as an add-on therapy to maximally-tolerated statin therapy for the reduction of cardiovascular risk among adults with elevated triglyceride (≥150 mg/dL) levels. Patients must also have either established cardiovascular disease or diabetes mellitus and two or more additional risk factors for cardiovascular disease. Vascepa (icosapent ethyl) is the first FDA-approved drug to reduce cardiovascular risk among adults with elevated triglyceride (≥150 mg/dL) levels as an add-on to maximally-tolerated statin therapy.^[1,2] (Note that in Canada it is approved for the indication of severe hypertriglyceridemia only.)

Vascepa’s (icosapent ethyl) approval for the two indications was based on two studies: MARINE, and REDUCE-IT.^[2]

The results of the MARINE study were used for the first approval. MARINE, with 151 patients enrolled, was a randomized, placebo controlled, double-blind, parallel-group study of adult patients with severe hypertriglyceridemia to assess the effects of Vascepa (icosapent ethyl) 4 grams per day. Patients whose baseline TG levels were between 500 and 2,000 mg/dL were enrolled in this study for 12 weeks. The effects were measured in changes in the major lipoprotein lipid parameters. Vascepa (icosapent ethyl) 4 grams per day reduced median TG, VLDL-C, and Apo B levels from baseline relative to placebo. The reduction in TG observed with Vascepa (icosapent ethyl) was not associated with elevations in LDL-C levels relative to placebo.^[2]

Results of the REDUCE-IT trial were used for the second indication, with 8,179 patients enrolled. The study was randomized to two arms, either 4 grams of icosapent ethyl or a placebo, with primary endpoint being the five-point MACE [major adverse cardiovascular events]: cardiovascular death, myocardial infarctions, stroke, hospitalization for unstable angina, or revascularization.^[3]

Primary endpoint: 25% relative risk reduction (RRR)^[4]

Secondary endpoints:^[4]

• Cardiovascular death or nonfatal heart attack: 25% RRR 
• Fatal or nonfatal heart attack: 31% RRR 
• Urgent or emergent revascularization: 35% RRR 
• Cardiovascular death: 20% RRR 
• Hospitalization for unstable angina: 32% RRR 
• Fatal or nonfatal stroke: 28% RRR 
• Total mortality, nonfatal heart attack or nonfatal stroke: 23% RRR

Vascepa (icosapent ethyl) was associated with an increased risk of atrial fibrillation or atrial flutter requiring hospitalization, where the incidence of atrial fibrillation was greater in patients with a previous history of atrial fibrillation or atrial flutter. Vascepa (icosapent ethyl) was also associated with an increased risk of bleeding events, where the incidence of bleeding was higher among patients who were also taking other medications that increase the risk of bleeding, such as aspirin, clopidogrel or warfarin at the same time. Musculoskeletal pain, peripheral edema (swelling of legs and hands), and arthralgia (joint pain) were the most common side effects reported in the clinical trials.^[1,2]

Vascepa’s (icosapent ethyl) active ingredient is the omega-3 fatty acid, derived from fish oil, and patients with allergic reaction to fish or shellfish are advised not to take it.^[1,2]

Please refer to the full prescribing information below for comprehensive information about the safety, effectiveness and adverse effects of Vascepa (icosapent ethyl) for the approved indications.^[1]

Reference

1. U.S. Food and Drug Administration. FDA approves use of drug to reduce risk of cardiovascular events in certain adult patient groups. 13/12/2019 (last update: 13/12/2019), cited on 14/02/2020.
2. Full prescribing information [FDA]: Vascepa (icosapent ethyl)[PDF], Amarin Pharma Inc., Dec. 2019.
3. MD Magazine. The REDUCE-IT trial and CV outcomes. 15/08/2019 (last update: 15/08/2019), cited on 14/02/2020.
4. Amarin Corporation. Investor relations / Vascepa® (icosapent ethyl) 26% reduction in key secondary composite endpoint of cardiovascular death, heart attacks and stroke demonstrated in REDUCE-IT™ supports 25% overall reduction in five-point major adverse cardiovascular event primary composite endpoint. 10/11/2018 (last update: 10/11/2018), cited on 14/02/2020.