Background: Icosapent ethyl (ICP), an ethyl ester of eicosapentaenoic acid (EPA), and omega-3 acid ethyl esters (DHA/EPA), comprised of ethyl esters of EPA and doxosahexaenoic acid (DHA), are approved as adjunctive therapy to statins for reducing adverse cardiovascular events (CV) in patients with CV risks. However, there are concerns regarding a potential association between ICP and atrial fibrillation (AF). This study evaluated the incidence of AF onset between ICP and DHA/EPA when used as adjuvant therapy with statins. Methods and Results: This retrospective study utilized administrative healthcare claims to analyze adult AF-naïve patients from one year preceding their first prescription for ICP or DHA/EPA. These patients were followed for two years, spanning from2013-2021. AF incidence was assessed during active treatment with either ICP or DHA/EPA as adjunct statin therapy. A propensity score (PS) matched cohort controlled for baseline characteristics and the effect of calendar year on the use of ICP or DHA/EPA. The cumulative incidence of AF was estimated using a product-limit estimator and compared between groups using a Cox proportional hazards regression model. The PS-matched cohort included 17,638 participants with a mean age 56 years, predominantly male (65.7% ICP vs. 64.5% DHA/EPA). Over two years, the cumulative incidence of AF from ICP and DHA/EPA was 5.32% and 3.99% respectively, resulting in a HR of 1.242 (95% CI: 1.061 to 1.455). Conclusions: In adult AF-naïve patients, ICP, when compared to DHA/EPA in conjunction with statin therapy, was associated with a significantly higher significant risk of developing AF.

The authors have declared no competing interest.

University of Utah Cardiovascular Clinical Pharmacology Fund

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The University of Illinois Chicago Institutional Review Board deemed the use of the database for this study exempt.

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