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We assessed the long-term outcome of both drugs for early rhythm control (ERC) in the EAST-AFNET 4 trial.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p>Patients randomized for ERC and treated with amiodarone or dronedarone were compared to other ERC-therapies. Patients receiving amiodarone or dronedarone at initial therapy (n\u2009=\u2009653\/1395) were older with more comorbidities and less paroxysmal atrial fibrillation (AF, 29%) compared to patients never receiving amiodarone or dronedarone (Amiodarone\/Dronedarone<jats:sup>never<\/jats:sup>, 43% paroxysmal AF). Patients treated with amiodarone had more often heart failure (HF, 42%) and persistent AF (40%) compared to patients treated with dronedarone (16% HF, 15% persistent AF) and Amiodarone\/Dronedarone<jats:sup>never<\/jats:sup> (25% HF, 22% persistent AF). 115\/398 amiodarone-treated patients (6.7\/100 patient-years) and 51\/255 dronedarone-treated patients (4.2\/100 patient-years) experienced a primary efficacy outcome (cardiovascular death, stroke, HF-hospitalization or acute coronary syndrome), while 98\/398 (5.3\/100 patient-years) and 43\/255 (3.4\/100 patient-years) experienced a primary safety outcome (death, stroke or serious adverse events related to rhythm-control therapy). Serious adverse events related to drug therapy were similar for amiodarone (1.4\/100 patient-years), dronedarone (1.2\/100 patient-years), and other ERC (0.8\/100 patient-years). Dronedarone (hazard ratio (HR) 0.5; CI 0.28\u20130.91), age (HR 1.05; CI 1.03\u20131.07), coronary artery disease (HR 1.84; CI 1.38\u20132.46) and stable HF (HR 1.66; CI 1.28\u20132.16) were associated with efficacy outcome upon multivariate Cox regression. Age (HR 1.07; CI 1.05\u20131.09) and left ventricular hypertrophy (HR 1.94; CI 1.13\u20133.32) were associated with safety outcome.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Early rhythm control using amiodarone or dronedarone rarely led to drug-related serious adverse events in EAST-AFNET 4.<\/jats:p>\n            <jats:p>\n              <jats:italic>Clinical Trial Registration<\/jats:italic>: ISRCTN04708680, NCT01288352, EudraCT2010-021258-20.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Graphical abstract<\/jats:title>\n            <jats:p>Central illustration<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00392-025-02637-0","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T14:17:47Z","timestamp":1747664267000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Safety and efficacy of amiodarone and dronedarone for early rhythm control in EAST-AFNET 4"],"prefix":"10.1007","author":[{"given":"Laura","family":"Rottner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc D.","family":"Lemoine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Eckardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Borof","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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Marc Lemoine received a travel grant Biosense Webster, a research grant from Farapulse, and was supported by the Research Promotion Fund of the Faculty of Medicine (Hamburg, \u201cClinician Scientist Program\u201d). Andreas Rillig received consultant fees from Medtronic, KODEX-EPD, Biosense Webster and travel grants and lecture fees from Medtronic, Cardiofocus, Biosense Webster, Abbott, Boehringer Ingelheim, Philips KODEX-EPD, Ablamap, Bayer, and Novartis. Andreas Metzner received speaker honoraria, travel grants and consultant fees from Medtronic, KODEX-EPD, Biosense Webster, Cardiofocus, and Boston scientific. Lars Eckardt received research support by the German heart foundation, consulting fees from Boston Scientific and lecture fees for various medical companies. John Camm received consulting fees from Sanofi and grant support and consulting fees from Abbott. Andreas Goette received lecture fees and consulting fees from Daiichi Sankyo, Sanofi Aventis, and Omeicos and lecture fees from Abbott, Bristol-Myers Squibb (BMS)\u2013Pfizer, Medtronic, Boehringer Ingelheim, AstraZeneca, and Berlin Chemie and was partially supported by EU Grant Horizon 2020 MAESTRIA Consortium; grant number 965286. Harry Crijns received grants from ZonMw (grant no. 104021005; RACE 9 Device-based rate vs. rhythm control treatment in patients with symptomatic recent-onset atrial fibrillation in the emergency department (RACE 9), consulting fees from InCarda Therapeutics, Roche, Sanofi, Atricure and honoraria from Medtronic. Andreas Goette received grants from Maestria (Grant EU 965286) and consulting fees from Sanofi-Aventis, Bayer, Astra Zeneca, Daiichi Sankyo, BMS\/Pfizer, Viofor, Boston Scientific, Medtronic, Menarini. Ulrich Schotten received grants (EU: CATCH ME, MAESTRIA, Personalize AF, REPAIR, Dutch Heart foundation, RACE V Embrace) and honoraria from Johnson and Johnson. He has patents for non-invasive classification of AF with ECG. Hein Heidb\u00fcchel received unconditional Research Grants through the University of Hassels and Antwerp, Abbott, Medtronic, Biotronik, Boston scientific, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Pfizer\u2013BMS, honoraria from Bayer, Biotronik, Bristol Myers Squibb, Daiichi Sankyo, Milestone Pharmaceuticals, Centrix India, CTI Germany, European Society of Cardiology, Medscape, Springer healthcare. Stefan Willems received grants from Boston Scientific and consulting fees: Boston Scientific, Abbott. Larissa Fabritz is listed as inventor of two patents (Atrial Fibrillation Therapy WO 2015140571, Markers for Atrial Fibrillation WO 2016012783). Renate Schnabel has received funding from the European Research Council (ERC) under the European Union\u2019s Horizon 2020 research and innovation programme under the grant agreement No 648131, from the European Union\u2019s Horizon 2020 research and innovation programme under the grant agreement no. 847770 (AFFECT-EU) and German Center for Cardiovascular Research (DZHK e.V.) (81Z1710103 and 81Z0710114); German Ministry of Research and Education (BMBF 01ZX1408A) and ERACoSysMed3 (031L0239). Wolfgang Seefried project funding German Heart Foundation. Lecture fees and advisory board fees from BMS\/Pfizer and Bayer. Christina Magnussen received grants from and research funding from German Center for Cardiovascular Research (Promotion of women scientists programme; FKZ 81X3710112); Deutsche Stiftung f\u00fcr Herzforschung; Dr. Rolf M. Schwiete Stiftung; NDD; Loewenstein Medical, honoraria from AstraZeneca, Novartis, Boehringer Ingelheim\/Lilly, Bayer, Pfizer, Sanofi, Aventis, Apontis, Abbott and support for attending meetings from AstraZeneca, Novartis, Boehringer Ingelheim\/Lilly, Novo Nordisk. Antonia Zapf receiving grant support from Biotronik. Paulus Kirchhof was partially supported by European Union AFFECT-AF (grant agreement 847770), and MAESTRIA (grant agreement 965286), British Heart Foundation (PG\/17\/30\/32961; PG\/ 20\/22\/35093; AA\/18\/2\/34218), German Center for Cardiovascular Research supported by the German Ministry of Education and Research (DZHK, grant numbers DZHK FKZ 81X2800182, 81Z0710116, and 81Z0710110), German Research Foundation (Ki 509167694), and Leducq Foundation. Paulus Kirchhof receives research support for basic, translational, and clinical research projects from European Union, British Heart Foundation, Leducq Foundation, Medical Research Council (UK), and German Centre for Cardiovascular Research, from several drug and device companies active in atrial fibrillation, and is listed as inventor on two issued patents held by University of Hamburg (Atrial Fibrillation Therapy WO 2015140571, Markers for Atrial Fibrillation WO 2016012783). Paulus Kirchhof receives research support for basic, translational, and clinical research projects from European Union, British Heart Foundation, Leducq Foundation, Medical Research Council (UK), and German Center for Cardiovascular Research, from several drug and device companies active in atrial fibrillation, and has received honoraria from several such companies in the past, but not in the last 3\u00a0years. Paulus Kirchhof is board member of the ESC and speaker of the board AFNET.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}