Icosapent Ethyl Effective in Lowering Cardiovascular Risk

Icosapent Ethyl: Effective Adjunct for Decreasing CV Events? Icosapent ethyl is a highly purified and stable form of EPA that is used as an adjunct to diet for hypertriglyceridemia in adults and has possible anti-inflammatory, antioxidant, and plaque-stabilizing properties. Authors of the REDUCE-IT trial sought to determine if icosapent ethyl has any effect on CV events. 

REDUCE-IT Study.² The REDUCE-IT study was a multicenter, randomized, placebo-controlled phase 3 trial that included 8179 participants with established CVD or diabetes and other risk factors. Participants were randomized to 2g of icosapent ethyl twice daily or a placebo and the median follow-up was 4.9 years. 

Lower Triglycerides, Little Impact on LDL with Icosapent Ethyl. There was a 19.7% greater reduction in triglycerides from baseline in the first year in the icosapent ethyl group vs placebo group. There was a 6.6% lower increase in LDL cholesterol level from baseline in the first year in the icosapent ethyl group vs placebo group. 

Ischemic Events Significantly Lower with Icosapent Ethyl. The primary endpoint was a composite of CV death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, and unstable angina. The risk of primary endpoint was lower by 25% among patients in the icosapent ethyl group vs placebo. A primary endpoint event occurred in 17.2% of patients in the icosapent ethyl group vs 22% in the placebo group. The number needed to treat in order to avoid 1 primary endpoint event was 21. 

Mortality Lower with Icosapent Ethyl. Mortality improved with icosapent ethyl vs placebo with a 20% lower risk of CV death and 13% lower risk of all cause death. There was no significant between-group differences in overall and serious adverse events. 

Atrial Fibrillation and Bleeding Higher with Icosapent Ethyl. There were no significant differences between icosapent ethyl group and placebo group in rates of adjudicated hemorrhagic stroke, serious central nervous system bleeding, or gastrointestinal bleeding (P= 0.55, P= 0.42, P= 0.15, respectively). 

Mixed Results on EPA: Studies are Ongoing. The results from REDUCE-IT may not generalize to other omega-3 fatty acid preparations, especially unregulated dietary supplements with variable EPA levels. Results contrast with other lipid trials that show a lack of benefit of omega-3 fatty acids.^3-5 There are currently 2 ongoing EPA trials: RESPECT-ERA⁶ (UMIN000012069) and EVAPORATE⁷ (NCT02926027).