Safety and efficacy of amiodarone and dronedarone for early rhythm control in EAST-AFNET 4

Laura Rottner; Marc D. Lemoine; Lars Eckardt; Katrin Borof; A. John Camm; Andreas Goette; Günter Breithardt; Andreas Metzner; Ulrich Schotten; Antonia Zapf; Hein Heidbüchel; Stephan Willems; Harry Crijns; Renate B. Schnabel; Larissa Fabritz; Christina Magnussen; Andreas Rillig; Paulus Kirchhof

doi:10.1007/s00392-025-02637-0

Safety and efficacy of amiodarone and dronedarone for early rhythm control in EAST-AFNET 4

Laura Rottner^*, Marc D. Lemoine, Lars Eckardt, Katrin Borof, A. John Camm, Andreas Goette, Günter Breithardt, Andreas Metzner, Ulrich Schotten, Antonia Zapf, Hein Heidbüchel, Stephan Willems, Harry Crijns, Renate B. Schnabel, Larissa Fabritz, Christina Magnussen, Andreas Rillig, Paulus Kirchhof

^*Corresponding author for this work

Cardiovascular Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

Aims: Concerns exist about the safety of amiodarone and dronedarone. We assessed the long-term outcome of both drugs for early rhythm control (ERC) in the EAST-AFNET 4 trial.

Methods and Results: 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 = 653/1395) were older with more comorbidities and less paroxysmal atrial fibrillation (AF, 29%) compared to patients never receiving amiodarone or dronedarone (Amiodarone/Dronedarone^never, 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^never (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 0.28–0.91), age (HR 1.05; CI 1.03–1.07), coronary artery disease (HR 1.84; CI 1.38–2.46) and stable HF (HR 1.66; CI 1.28–2.16) were associated with efficacy outcome upon multivariate Cox regression. Age (HR 1.07; CI 1.05–1.09) and left ventricular hypertrophy (HR 1.94; CI 1.13–3.32) were associated with safety outcome.

Conclusion: Early rhythm control using amiodarone or dronedarone rarely led to drug-related serious adverse events in EAST-AFNET 4.

Clinical Trial Registration: ISRCTN04708680, NCT01288352, EudraCT2010-021258-20.

Original language	English
Article number	e011585
Number of pages	16
Journal	Clinical Research in Cardiology
Early online date	19 May 2025
DOIs	https://doi.org/10.1007/s00392-025-02637-0
Publication status	E-pub ahead of print - 19 May 2025

Bibliographical note

Publisher Copyright:
© The Author(s) 2025.

Keywords

Amiodarone
Anti-arrhythmic drug therapy
Atrial fibrillation
Dronedarone
Safety

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1007/s00392-025-02637-0Licence: Creative Commons: Attribution (CC BY)

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MAESTRIA: Machine Learning Artificial Intelligence Early Detection Stroke Atrial Fibrillation
Kirchhof, P. (Researcher), Gkoutos, G. (Principal Investigator) & Fabritz, L. (Researcher)
European Commission
1/03/21 → 31/08/26
Project: EU
Defining clusters of patients with atrial fibrillation at risk of heart failure and death
Kirchhof, P. (Principal Investigator) & Gkoutos, G. (Researcher)
British Heart Foundation
1/07/20 → 30/06/21
Project: Research
Use of engineered substrates to promote stem cell cardiac differentiation: A model to study cardiac diseases - Reyat - Sub-project of 21502
Reyat, J. (Principal Investigator)
British Heart Foundation
1/10/19 → 31/03/21
Project: Research
Impact of chronic intermittent hypoxia on atrial resting membrane potential and Na 1.5 channel function: A new mechanism for causing atrial fibrillation
Kirchhof, P. (Principal Investigator) & Holmes, A. (Co-Investigator)
British Heart Foundation
1/10/17 → 18/07/21
Project: Research
H2020_COLLAB(IMI-JU)_BIGDATA@HEART
Kotecha, D. (Principal Investigator) & Kirchhof, P. (Co-Investigator)
European Commission
1/03/17 → 28/02/23
Project: Research
H2020_COLLAB_CATCH ME_(LEAD)
Kirchhof, P. (Principal Investigator), Fabritz, L. (Co-Investigator), Hemming, K. (Co-Investigator) & Deeks, J. (Co-Investigator)
European Commission
1/05/15 → 30/04/19
Project: EU
Understanding the function of PITX2 in the adult left atrium
Kirchhof, P. (Principal Investigator) & Fabritz, L. (Co-Investigator)
British Heart Foundation
4/11/13 → 3/11/18
Project: Research

Cite this

Rottner, L., Lemoine, M. D., Eckardt, L., Borof, K., Camm, A. J., Goette, A., Breithardt, G., Metzner, A., Schotten, U., Zapf, A., Heidbüchel, H., Willems, S., Crijns, H., Schnabel, R. B., Fabritz, L., Magnussen, C., Rillig, A., & Kirchhof, P. (2025). Safety and efficacy of amiodarone and dronedarone for early rhythm control in EAST-AFNET 4. Clinical Research in Cardiology, Article e011585. Advance online publication. https://doi.org/10.1007/s00392-025-02637-0

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title = "Safety and efficacy of amiodarone and dronedarone for early rhythm control in EAST-AFNET 4",

abstract = "Aims: Concerns exist about the safety of amiodarone and dronedarone. We assessed the long-term outcome of both drugs for early rhythm control (ERC) in the EAST-AFNET 4 trial. Methods and Results: 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 = 653/1395) were older with more comorbidities and less paroxysmal atrial fibrillation (AF, 29\%) compared to patients never receiving amiodarone or dronedarone (Amiodarone/Dronedaronenever, 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/Dronedaronenever (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 0.28–0.91), age (HR 1.05; CI 1.03–1.07), coronary artery disease (HR 1.84; CI 1.38–2.46) and stable HF (HR 1.66; CI 1.28–2.16) were associated with efficacy outcome upon multivariate Cox regression. Age (HR 1.07; CI 1.05–1.09) and left ventricular hypertrophy (HR 1.94; CI 1.13–3.32) were associated with safety outcome. Conclusion: Early rhythm control using amiodarone or dronedarone rarely led to drug-related serious adverse events in EAST-AFNET 4. Clinical Trial Registration: ISRCTN04708680, NCT01288352, EudraCT2010-021258-20.",

keywords = "Amiodarone, Anti-arrhythmic drug therapy, Atrial fibrillation, Dronedarone, Safety",

author = "Laura Rottner and Lemoine, \{Marc D.\} and Lars Eckardt and Katrin Borof and Camm, \{A. John\} and Andreas Goette and G{\"u}nter Breithardt and Andreas Metzner and Ulrich Schotten and Antonia Zapf and Hein Heidb{\"u}chel and Stephan Willems and Harry Crijns and Schnabel, \{Renate B.\} and Larissa Fabritz and Christina Magnussen and Andreas Rillig and Paulus Kirchhof",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = may,

day = "19",

doi = "10.1007/s00392-025-02637-0",

language = "English",

journal = "Clinical Research in Cardiology",

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Rottner, L, Lemoine, MD, Eckardt, L, Borof, K, Camm, AJ, Goette, A, Breithardt, G, Metzner, A, Schotten, U, Zapf, A, Heidbüchel, H, Willems, S, Crijns, H, Schnabel, RB, Fabritz, L, Magnussen, C, Rillig, A & Kirchhof, P 2025, 'Safety and efficacy of amiodarone and dronedarone for early rhythm control in EAST-AFNET 4', Clinical Research in Cardiology. https://doi.org/10.1007/s00392-025-02637-0

TY - JOUR

T1 - Safety and efficacy of amiodarone and dronedarone for early rhythm control in EAST-AFNET 4

AU - Rottner, Laura

AU - Lemoine, Marc D.

AU - Eckardt, Lars

AU - Borof, Katrin

AU - Camm, A. John

AU - Goette, Andreas

AU - Breithardt, Günter

AU - Metzner, Andreas

AU - Schotten, Ulrich

AU - Zapf, Antonia

AU - Heidbüchel, Hein

AU - Willems, Stephan

AU - Crijns, Harry

AU - Schnabel, Renate B.

AU - Fabritz, Larissa

AU - Magnussen, Christina

AU - Rillig, Andreas

AU - Kirchhof, Paulus

PY - 2025/5/19

Y1 - 2025/5/19

N2 - Aims: Concerns exist about the safety of amiodarone and dronedarone. We assessed the long-term outcome of both drugs for early rhythm control (ERC) in the EAST-AFNET 4 trial. Methods and Results: 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 = 653/1395) were older with more comorbidities and less paroxysmal atrial fibrillation (AF, 29%) compared to patients never receiving amiodarone or dronedarone (Amiodarone/Dronedaronenever, 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/Dronedaronenever (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 0.28–0.91), age (HR 1.05; CI 1.03–1.07), coronary artery disease (HR 1.84; CI 1.38–2.46) and stable HF (HR 1.66; CI 1.28–2.16) were associated with efficacy outcome upon multivariate Cox regression. Age (HR 1.07; CI 1.05–1.09) and left ventricular hypertrophy (HR 1.94; CI 1.13–3.32) were associated with safety outcome. Conclusion: Early rhythm control using amiodarone or dronedarone rarely led to drug-related serious adverse events in EAST-AFNET 4. Clinical Trial Registration: ISRCTN04708680, NCT01288352, EudraCT2010-021258-20.

AB - Aims: Concerns exist about the safety of amiodarone and dronedarone. We assessed the long-term outcome of both drugs for early rhythm control (ERC) in the EAST-AFNET 4 trial. Methods and Results: 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 = 653/1395) were older with more comorbidities and less paroxysmal atrial fibrillation (AF, 29%) compared to patients never receiving amiodarone or dronedarone (Amiodarone/Dronedaronenever, 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/Dronedaronenever (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 0.28–0.91), age (HR 1.05; CI 1.03–1.07), coronary artery disease (HR 1.84; CI 1.38–2.46) and stable HF (HR 1.66; CI 1.28–2.16) were associated with efficacy outcome upon multivariate Cox regression. Age (HR 1.07; CI 1.05–1.09) and left ventricular hypertrophy (HR 1.94; CI 1.13–3.32) were associated with safety outcome. Conclusion: Early rhythm control using amiodarone or dronedarone rarely led to drug-related serious adverse events in EAST-AFNET 4. Clinical Trial Registration: ISRCTN04708680, NCT01288352, EudraCT2010-021258-20.

KW - Amiodarone

KW - Anti-arrhythmic drug therapy

KW - Atrial fibrillation

KW - Dronedarone

KW - Safety

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DO - 10.1007/s00392-025-02637-0

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JO - Clinical Research in Cardiology

JF - Clinical Research in Cardiology

M1 - e011585

ER -

Safety and efficacy of amiodarone and dronedarone for early rhythm control in EAST-AFNET 4

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

Fingerprint

Projects

MAESTRIA: Machine Learning Artificial Intelligence Early Detection Stroke Atrial Fibrillation

Defining clusters of patients with atrial fibrillation at risk of heart failure and death

Use of engineered substrates to promote stem cell cardiac differentiation: A model to study cardiac diseases - Reyat - Sub-project of 21502

Impact of chronic intermittent hypoxia on atrial resting membrane potential and Na 1.5 channel function: A new mechanism for causing atrial fibrillation

H2020_COLLAB(IMI-JU)_BIGDATA@HEART

H2020_COLLAB_CATCH ME_(LEAD)

Understanding the function of PITX2 in the adult left atrium

Cite this