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. 2025 Sep 22:zwaf602.
doi: 10.1093/eurjpc/zwaf602. Online ahead of print.

Benefit of Icosapent Ethyl Across Types and Sizes of Myocardial Infarction in REDUCE-IT

Chen Gurevitz  1 , Deepak L Bhatt  1 , Robert P Giugliano  2 , Ph Gabriel Steg  3 , Michael Miller  4 , Eliot A Brinton  5 , Terry A Jacobson  6 , Steven B Ketchum  7 , Armando Lira Pineda  7 , Ralph T Doyle Jr  7 , Gabriella Giugliano  8 , R Preston Mason  9 , Jean-Claude Tardif  10 , Fabrice M A C Martens  11 , Christie M Ballantyne  12 , Matthew J Budoff  13 , C Michael Gibson  14
Affiliations

Benefit of Icosapent Ethyl Across Types and Sizes of Myocardial Infarction in REDUCE-IT

Chen Gurevitz et al. Eur J Prev Cardiol. .

Abstract

Aims: We studied the efficacy and safety of icosapent ethyl (IPE) 4g daily in reducing the risk of myocardial infarction (MI) across different MI subtypes and sizes, among REDUCE-IT high-risk patients with hypertriglyceridemia.

Methods: REDUCE-IT was a phase 3b, double-blind multicenter trial. Patients with established CVD or diabetes who were treated with statins and had moderate hypertriglyceridemia were randomized to receive IPE 4g daily or placebo. The current analysis focused on MI subtypes (fatal MI, nonfatal MI, ST-segment elevation MI (STEMI), non-STEMI (NSTEMI)), as well as MI size (measured by multiples of troponin upper limit of normal) and MI-related complications. Safety outcomes included treatment emergent adverse events (TEAEs), bleeding, atrial fibrillation, and flutter.

Results: At 5.7 years follow-up, MI incidence was lower with IPE compared with placebo (8.6% vs 12.0%), hazard ratio (HR) 0.69 (95% CI 0.58-0.81, P<0.0001). STEMI incidence was lower with IPE (2.7% vs 3.9%, HR 0.60, 95% CI 0.44-0.81, P=0.0008), as was NSTEMI incidence (5.9% vs 7.8%, HR 0.73, 95% CI 0.60-0.89, P=0.001). Fatal and nonfatal MIs were reduced with IPE (HR 0.55, 95% CI 0.30-1.01, P=0.05 and HR 0.70, 95% CI 0.59-0.82, P<0.0001, respectively). Stratification by size revealed IPE reduced most MIs, but the protective effect was higher for larger MIs (P<0.0001). Further analyses showed benefits in MI-related outcomes, including reductions in spontaneous MI and MI-related complications. Among patients who developed MI, safety outcomes showed no significant increase in serious bleeding, atrial fibrillation or flutter, or adverse events with IPE.

Conclusion: IPE significantly reduced MI across most subtypes and sizes in statin-treated patients with elevated triglycerides at increased cardiovascular risk.

Trial registration: ClinicalTrials.gov Identifier NCT01492361.

Keywords: eicosapentaenoic acid; hypertriglyceridemia; icosapent ethyl; myocardial infarction.

Plain language summary

Among patients at high risk for heart and vascular diseases who are receiving statins, icosapent ethyl (IPE) 4 g daily as an added treatment significantly lowers the risk of heart attack, also known as myocardial infarction (MI), across sizes and subtypes, including ST-segment elevation MI (STEMI) and non-STEMI (NSTEMI).In this secondary analysis of REDUCE-IT, IPE 4 g daily significantly reduced the risk of heart attack by 31% compared with placebo.IPE reduced incidence of large heart attacks by up to 65% and was associated with fewer related complications, including heart attack-related cardiac arrests and resuscitated heart attacks.

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