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).
Take Home Points. The REDUCE-IT trial showed lower ischemic events and lower mortality, with improved triglycerides and little effect on LDL in patients with hypertriglyceridemia on appropriate doses of statins. Atrial fibrillation and serious bleeding were higher with icosapent ethyl. The results contrast with other trials that show no CV benefit with omega-3 fatty acids; ongoing trials may clarify the role of EPA in the prevention of CV events.
References:
1. Yokoyama M, Origasa H, Matsuzaki M, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): A randomised open-label, blinded endpoint analysis. Lancet. 2007;369:1090-1098.
2. Bhatt DL, Steg PG, Miller M, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2018.
3. Aung T, Halsey J, Kromhout D, et al. Associations of omega-3 fatty acid supplement use with cardiovascular disease risks: Meta-analysis of 10 trials involving 77â¯917 individuals. JAMA Cardiol. 2018;3:225-234.
4. ORIGIN Trial Investigators, Bosch J, Gerstein HC, et al. n-3 fatty acids and cardiovascular outcomes in patients with dysglycemia. N Engl J Med. 2012;367:309-318.
5. ASCEND Study Collaborative Group, Bowman L, Mafham M, et al. Effects of n-3 fatty acid supplements in diabetes mellitus. N Engl J Med. 2018;379:1540-1550.
What effect does icosapent ethyl, a highly purified and stable form of fish oil, have on cardiovascular events? That is the question authors the REDUCE-IT trial sought to answer. What did they find? And how will their results impact future research and clinical practice? Click through the slideshow below to find out.
