Cardiovascular Benefits of Icosapent Ethyl in Patients With and Without Atrial Fibrillation in REDUCE-IT

• Authors: Terry Jacobson, Emory University; B Olshansky, Univ Iowa Hosp & Clin; DLL Bhatt, Icahn Sch Med Mt Sinai Hlth Syst; M Miller, Crescenz Vet Affairs Med Ctr; PG Steg, Hop Bichat Claude Bernard; EAA Brinton, Utah Lipid Ctr; SBB Ketchum, Amarin Pharm Inc; RTT Doyle Jr, Amarin Pharm Inc; RAA Juliano, Amarin Pharm Inc; L Jiao, Amarin Pharm Inc; PRR Kowey, Lankenau Inst Med Res; JAA Reiffel, Columbia University; J-C Tardif; CMM Ballantyne; MKK Chung; I REDUCE-IT
• Journal Title: JOURNAL OF THE AMERICAN HEART ASSOCIATION
• Volume: Volume 12, Number 5
• Publisher: WILEY | 2023-03-07, Pages e026756-e026756
• Type of Work: Article
• Publisher DOI: http://doi.org/10.1161/JAHA.121.026756
• Keywords: Science & Technology; Life Sciences & Biomedicine; Cardiac & Cardiovascular Systems; Cardiovascular System & Cardiology; atrial fibrillation; bleeding; eicosapentaenoic acid; icosapent ethyl; prevention; POLYUNSATURATED FATTY-ACID; FISH-OIL; ISCHEMIC EVENTS; OMEGA-3-FATTY-ACIDS; SUPPLEMENTATION; HEART; BLOCK; ELECTROPHYSIOLOGY; ARRHYTHMIAS; PREVENTION

Abstract

BACKGROUND: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial), icosapent ethyl (IPE) versus placebo) reduced cardiovascular death, myocardial infarction, stroke, coronary revascularization, or unstable angina requiring hospitalization, but was associated with increased atrial fibrillation/atrial flutter (AF) hospitalization (3.1% IPE versus 2.1% placebo; P=0.004). METHODS AND RESULTS: We performed post hoc efficacy and safety analyses of patients with or without prior AF (before randomi-zation) and with or without in-study time-varying AF hospitalization to assess relationships of IPE (versus placebo) and outcomes. In-study AF hospitalization event rates were higher in patients with prior AF (12.5% versus 6.3%, IPE versus placebo; P=0.007) versus without prior AF (2.2% versus 1.6%, IPE versus placebo; P=0.09). Serious bleeding rates trended higher in patients with (7.3% versus 6.0%, IPE versus placebo; P=0.59) versus without prior AF (2.3% versus 1.7%, IPE versus placebo; P=0.08). With IPE, serious bleeding trended higher regardless of prior AF (interaction P value [Pint ]=0.61) or postrandomization AF hospitalization (Pint =0.66). Patients with prior AF (n=751, 9.2%) versus without prior AF (n=7428, 90.8%) had similar relative risk reductions of the primary composite and key secondary composite end points with IPE versus placebo (Pint =0.37 and Pint =0.55, respectively). CONCLUSIONS: In REDUCE-IT, in-study AF hospitalization rates were higher in patients with prior AF especially in those randomized to IPE. Although serious bleeding trended higher in those randomized to IPE versus placebo over the course of the study, serious bleeding was not different regardless of prior AF or in-study AF hospitalization. Patients with prior AF or in-study AF hospitalization had consistent relative risk reductions across primary, key secondary, and stroke end points with IPE. REGISTRATION: URL: https://clinicaltrials.gov/ct2/show/NCT01492361; Unique Identifier: NCT01492361.