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

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 randomization) 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 [ P int ]=0.61) or postrandomization AF hospitalization ( P int =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 ( P int =0.37 and P int =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.