Comparative Risk of Atrial Fibrillation Onset in Statin‐Treated Patients Initiating Icosapent Ethyl and Omega‐3 Acid Ethyl Esters: A Retrospective Cohort Study

Background Icosapent ethyl (IPE) and omega‐3‐acid ethyl esters (docosahexaenoic acid [DHA]/eicosapentaenoic acid [EPA]) are approved as adjunct therapies to statins for reducing cardiovascular events in at‐risk patients. However, concerns remain regarding a potential link between IPE and atrial fibr...

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Main Authors: Jyotirmoy Sarker, Michael Kim, Samantha Patton, Przemysław B. Radwański, Mark A. Munger, Kibum Kim
Format: Article
Language:English
Published: Wiley 2025-08-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
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Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.124.038846
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author Jyotirmoy Sarker
Michael Kim
Samantha Patton
Przemysław B. Radwański
Mark A. Munger
Kibum Kim
author_facet Jyotirmoy Sarker
Michael Kim
Samantha Patton
Przemysław B. Radwański
Mark A. Munger
Kibum Kim
author_sort Jyotirmoy Sarker
collection DOAJ
description Background Icosapent ethyl (IPE) and omega‐3‐acid ethyl esters (docosahexaenoic acid [DHA]/eicosapentaenoic acid [EPA]) are approved as adjunct therapies to statins for reducing cardiovascular events in at‐risk patients. However, concerns remain regarding a potential link between IPE and atrial fibrillation (AF). We compared the risk of AF onset in patients who initiated IPE versus DHA/EPA as adjuncts to statin therapy. Methods We conducted a retrospective cohort study using the Merative MarketScan Commercial Claims and Medicare Supplemental database in the United States. An active‐comparator, new‐user study design was applied. Adults diagnosed with dyslipidemia and receiving statin therapy who initiated IPE or DHA/EPA between January 2013 and June 2021 were identified. A propensity score–matched cohort was created using baseline demographic characteristics, comorbidities, and medication dispensing records, with exact matching on therapy initiation period. Patients were followed for up to 2 years while they were on IPE or DHA/EPA therapy to identify incident AF. Cumulative incidence was estimated using Kaplan–Meier methods, and risks between groups were compared using Cox proportional hazards analysis. Results The propensity score–matched cohort included 17 635 participants, with a mean age of 55 years, and was predominantly men (65.4%). Over 2 years, the cumulative incidence of AF from IPE and DHA/EPA was 5.20% (95% CI, 4.62%–5.84%) and 4.07% (95% CI, 3.58%–4.62%) respectively, resulting in a hazard ratio of 1.21 (95% CI, 1.03–1.42). Conclusions These findings suggest that, in adult patients who are AF naïve, IPE may be associated with a higher risk of AF compared with DHA/EPA when used as add‐on therapy with statins.
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spelling doaj-art-bdfbc86449ef44e7ae26c4d212d259e72025-08-20T04:02:14ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802025-08-01141510.1161/JAHA.124.038846Comparative Risk of Atrial Fibrillation Onset in Statin‐Treated Patients Initiating Icosapent Ethyl and Omega‐3 Acid Ethyl Esters: A Retrospective Cohort StudyJyotirmoy Sarker0Michael Kim1Samantha Patton2Przemysław B. Radwański3Mark A. Munger4Kibum Kim5Department of Pharmacy Systems Outcomes and Policy, University of Illinois Chicago Chicago IL USADepartment of Pharmacy Systems Outcomes and Policy, University of Illinois Chicago Chicago IL USADepartment of Pharmacotherapy University of Utah Health Salt Lake City UT USADepartment of Physiology and Cell Biology The Ohio State University Columbus OH USADepartment of Pharmacotherapy University of Utah Health Salt Lake City UT USADepartment of Pharmacy Systems Outcomes and Policy, University of Illinois Chicago Chicago IL USABackground Icosapent ethyl (IPE) and omega‐3‐acid ethyl esters (docosahexaenoic acid [DHA]/eicosapentaenoic acid [EPA]) are approved as adjunct therapies to statins for reducing cardiovascular events in at‐risk patients. However, concerns remain regarding a potential link between IPE and atrial fibrillation (AF). We compared the risk of AF onset in patients who initiated IPE versus DHA/EPA as adjuncts to statin therapy. Methods We conducted a retrospective cohort study using the Merative MarketScan Commercial Claims and Medicare Supplemental database in the United States. An active‐comparator, new‐user study design was applied. Adults diagnosed with dyslipidemia and receiving statin therapy who initiated IPE or DHA/EPA between January 2013 and June 2021 were identified. A propensity score–matched cohort was created using baseline demographic characteristics, comorbidities, and medication dispensing records, with exact matching on therapy initiation period. Patients were followed for up to 2 years while they were on IPE or DHA/EPA therapy to identify incident AF. Cumulative incidence was estimated using Kaplan–Meier methods, and risks between groups were compared using Cox proportional hazards analysis. Results The propensity score–matched cohort included 17 635 participants, with a mean age of 55 years, and was predominantly men (65.4%). Over 2 years, the cumulative incidence of AF from IPE and DHA/EPA was 5.20% (95% CI, 4.62%–5.84%) and 4.07% (95% CI, 3.58%–4.62%) respectively, resulting in a hazard ratio of 1.21 (95% CI, 1.03–1.42). Conclusions These findings suggest that, in adult patients who are AF naïve, IPE may be associated with a higher risk of AF compared with DHA/EPA when used as add‐on therapy with statins.https://www.ahajournals.org/doi/10.1161/JAHA.124.038846atrial fibrillationicosapent ethylomega‐3‐acid ethyl estersretrospective cohort study
spellingShingle Jyotirmoy Sarker
Michael Kim
Samantha Patton
Przemysław B. Radwański
Mark A. Munger
Kibum Kim
Comparative Risk of Atrial Fibrillation Onset in Statin‐Treated Patients Initiating Icosapent Ethyl and Omega‐3 Acid Ethyl Esters: A Retrospective Cohort Study
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
atrial fibrillation
icosapent ethyl
omega‐3‐acid ethyl esters
retrospective cohort study
title Comparative Risk of Atrial Fibrillation Onset in Statin‐Treated Patients Initiating Icosapent Ethyl and Omega‐3 Acid Ethyl Esters: A Retrospective Cohort Study
title_full Comparative Risk of Atrial Fibrillation Onset in Statin‐Treated Patients Initiating Icosapent Ethyl and Omega‐3 Acid Ethyl Esters: A Retrospective Cohort Study
title_fullStr Comparative Risk of Atrial Fibrillation Onset in Statin‐Treated Patients Initiating Icosapent Ethyl and Omega‐3 Acid Ethyl Esters: A Retrospective Cohort Study
title_full_unstemmed Comparative Risk of Atrial Fibrillation Onset in Statin‐Treated Patients Initiating Icosapent Ethyl and Omega‐3 Acid Ethyl Esters: A Retrospective Cohort Study
title_short Comparative Risk of Atrial Fibrillation Onset in Statin‐Treated Patients Initiating Icosapent Ethyl and Omega‐3 Acid Ethyl Esters: A Retrospective Cohort Study
title_sort comparative risk of atrial fibrillation onset in statin treated patients initiating icosapent ethyl and omega 3 acid ethyl esters a retrospective cohort study
topic atrial fibrillation
icosapent ethyl
omega‐3‐acid ethyl esters
retrospective cohort study
url https://www.ahajournals.org/doi/10.1161/JAHA.124.038846
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