Abstract 4140072: Icosapent Ethyl-Associated New Atrial Fibrillation Incidence compared to Omega-3 Fatty Acids: An Observational Cohort Study

Introduction: Icosapent ethyl (IE), an ethyl ester derivative of eicosapentanoic acid (EPA), and omega-3 acid ethyl esters, an ethyl ester derivative of both EPA and docosahexaenoic acid (DHA), are approved as adjunct to statin therapy for reducing MACE in patients with elevated triglyceride levels. There are concerns regarding atrial fibrillation (AF) risk associated with IE. This study aims to assess the incidence of AF while receiving IE versus omega-3-acid ethyl esters (DHA/EPA), both alongside baseline statin therapy. Methods: In this retrospective cohort study, we used data from the Merative MarketScan Commercial Claims and Medicare Supplemental Databases (2013-2021). Adult patients on statin therapy who initiated either IE or DHA/EPA were identified using outpatient dispensing records. Patients with an AF diagnosis during the one-year baseline period were excluded. Patients were followed for up to two years to assess the incidence of AF. Censoring occurred if there was treatment discontinuation, switching between treatments, end of enrollment, or end of the study. Patients experiencing events or being censored within the first 30 days were also excluded. Propensity score matching was used to create comparable groups, with exact matching on time periods (2013-2015, 2016-2018, and 2019-2021). Using Cox proportional hazard regression model, we calculated hazards ratio of the onset of AF for IE versus DHA/EPA. Results: The analytic cohort consisted of 17,638 matched pairs. Patients in both groups had a median age of 56 years. Male patients accounted for a 65.7% of the IE group and 64.5% of the DHA/EPA group. Baseline cardiovascular risk factors were well matched between both groups. The 2-year cumulative incidence of AF for IE and DHA/EPA groups were 5.322% and 3.994%, respectively, resulting in a HR of 1.257 [95% CI,1.159-1.364], p=0.0032. (Figure 1) Conclusions: IE is associated with a higher risk of AF compared to DHA/EPA combined products, indicating the need for careful risk-benefit discussion between clinicians and patients considering IE therapy.