Reduction in Revascularization With Icosapent Ethyl Insights From REDUCE-IT Revascularization Analyses

• Type of Material: Article
• Authors: Benjamin E. Peterson, Harvard Medical School; Deepak L. Bhatt, Harvard Medical School; Ph. Gabriel Steg, Université de Paris; Michael Miller, University of Maryland School of Medicine; Eliot A. Brinton, Utah Lipid Center; Terry Jacobson, Emory University; Steven B. Ketchum, Amarin Pharma, Inc.; Rebecca A. Juliano, Amarin Pharma, Inc.; Lixia Jiao, Amarin Pharma, Inc.; Ralph T. Doyle, Amarin Pharma, Inc.; Craig Granowitz, Amarin Pharma, Inc.; C. Michael Gibson, Baim Clinical Research Institute; Duane Pinto, Baim Clinical Research Institute; Robert P. Giugliano, Harvard Medical School; Matthew J. Budoff, David Geffen School of Medicine; Jean-Claude Tardif, Université de Montréal; Subodh Verma, University of Toronto; Christie M. Ballantyne, Baylor College of Medicine
• Language: English
• Date: 2021-01-05
• Publisher: LIPPINCOTT WILLIAMS & WILKINS
• Publication Version: Final Published Version
• Copyright Statement: © 2020 The Authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1161/CIRCULATIONAHA.120.050276
• Title of Journal or Parent Work: CIRCULATION
• Volume: 143
• Issue: 1
• Start Page: 33
• End Page: 44
• Grant/Funding Information: The main REDUCE-IT trial and this analysis have been funded by Amarin.
• Keywords: CORONARY INTERVENTION; EVENTS; LIPOPROTEINS; HYPERCHOLESTEROLEMIC PATIENTS; THERAPY; eicosapentaenoic acid; ATHEROSCLEROTIC CARDIOVASCULAR-DISEASE; Science & Technology; Cardiovascular System & Cardiology; Peripheral Vascular Disease; EICOSAPENTAENOIC ACID; TRIGLYCERIDES; Cardiac & Cardiovascular Systems; prevention & control; icosapent ethyl; FATTY-ACIDS; RISK; Life Sciences & Biomedicine; myocardial revascularization
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

BACKGROUND: Patients with elevated triglycerides despite statin therapy have increased risk for ischemic events, including coronary revascularizations. METHODS: REDUCE-IT (The Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial), a multicenter, double-blind, placebo-controlled trial, randomly assigned statin-treated patients with elevated triglycerides (135-499 mg/dL), controlled low-density lipoprotein (41-100 mg/dL), and either established cardiovascular disease or diabetes plus other risk factors to receive icosapent ethyl 4 g/d or placebo. The primary and key secondary composite end points were significantly reduced. Prespecified analyses examined all coronary revascularizations, recurrent revascularizations, and revascularization subtypes. RESULTS: A total of 8179 randomly assigned patients were followed for 4.9 years (median). First revascularizations were reduced to 9.2% (22.5/1000 patient-years) with icosapent ethyl versus 13.3% (33.7/1000 patient-years) with placebo (hazard ratio, 0.66 [95% CI, 0.58-0.76]; P<0.0001; number needed to treat for 4.9 years=24); similar reductions were observed in total (first and subsequent) revascularizations (negative binomial rate ratio, 0.64 [95% CI, 0.56-0.74]; P<0.0001), and across elective, urgent, and emergent revascularizations. Icosapent ethyl significantly reduced percutaneous coronary intervention (hazard ratio, 0.68 [95% CI, 0.59-0.79]; P<0.0001) and coronary artery bypass grafting (hazard ratio, 0.61 [95% CI, 0.45-0.81]; P=0.0005). CONCLUSIONS: Icosapent ethyl reduced the need for first and subsequent coronary revascularizations in statin-treated patients with elevated triglycerides and increased cardiovascular risk. To our knowledge, icosapent ethyl is the first non-low-density lipoprotein-lowering treatment that has been shown to reduce coronary artery bypass grafting in a blinded, randomized trial.