Comparative Risk of the Onset of Atrial Fibrillation after Icosapent Ethyl versus Omega-3-Acid-Ethyl-Esters Adjuvant to Statins

BackgroundIcosapent 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 ResultsThis retrospective study utilized administrative healthcare claims to analyze adult AF-naive 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). ConclusionsIn adult AF-naive patients, ICP, when compared to DHA/EPA in conjunction with statin therapy, was associated with a significantly higher significant risk of developing AF. RESEARCH PERSPECTIVEO_ST_ABSWhat is New?C_ST_ABSO_LIDoes icopasent ethyl (ICP), an ethyl ester of eicosapentaenoic acid (EPA) and omega-3 acid ethyl esters comprised of ethyl esters of EPA and doxosahexaenoic acid (DHA) in atrial fibrillation (AF)-naive patients taking statins increase the incidence of AF? C_LIO_LIOver 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). C_LIO_LIIn adult AF-naive patients, ICP, when compared to DHA/EPA in conjunction with statin therapy was associated with a higher significant risk of developing AF. C_LI What Question Should be Addressed Next?O_LIWhat should be considered as clinical and demographic factors in identifying patients at risk of atrial fibrillation prior to being prescribed ICP or DHA/EPA agents. C_LIO_LIInvestigation into the underlying mechanism of the increase in atrial fibrillation with marine omega-3 ethyl esters should continue. C_LIO_LIUnderstanding AF outcomes from ICP or DHA/EPA use including AF burden, need for AF medical or electrophysiological interventions, and health-care total costs. C_LI