胺碘酮和决奈达隆用于EAST-AFNET 4研究中早期节律控制的安全性和有效性。

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

作者信息

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

机构信息

Department of Cardiology, University Heart and Vascular Center UKE Hamburg, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.

German Center for Cardiovascular Research, Partner Site Hamburg/Lübeck/Kiel, Hamburg, Germany.

出版信息

Clin Res Cardiol. 2025 May 19. doi: 10.1007/s00392-025-02637-0.

DOI:10.1007/s00392-025-02637-0

PMID:40387892

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, 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 (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.

摘要

目的

胺碘酮和决奈达隆的安全性备受关注。我们在EAST-AFNET 4试验中评估了这两种药物用于早期节律控制（ERC）的长期疗效。

方法与结果

将随机接受ERC并接受胺碘酮或决奈达隆治疗的患者与其他ERC治疗方法进行比较。与从未接受过胺碘酮或决奈达隆治疗的患者相比，初始治疗时接受胺碘酮或决奈达隆治疗的患者（n = 653/1395）年龄更大，合并症更多，阵发性心房颤动（AF）更少（29%）（胺碘酮/决奈达隆组阵发性AF为43%）。与接受决奈达隆治疗的患者（16%发生心力衰竭（HF），15%为持续性AF）和胺碘酮/决奈达隆组（25%发生HF，22%为持续性AF）相比，接受胺碘酮治疗的患者更常出现心力衰竭（42%）和持续性AF（40%）。115/398例接受胺碘酮治疗的患者（6.7/100患者年）和51/255例接受决奈达隆治疗的患者（4.2/100患者年）出现了主要疗效结局（心血管死亡、中风、HF住院或急性冠状动脉综合征），而98/398例（5.3/100患者年）和43/255例（3.4/100患者年）出现了主要安全性结局（死亡、中风或与节律控制治疗相关的严重不良事件）。与药物治疗相关的严重不良事件在胺碘酮组（1.4/100患者年）、决奈达隆组（1.2/100患者年）和其他ERC组（0.8/100患者年）中相似。决奈达隆（风险比（HR）0.5；95%置信区间（CI）0.28 - 0.91）、年龄（HR 1.05；CI 1.03 - 1.07）、冠状动脉疾病（HR 1.84；CI 1.38 - 2.46）和稳定型HF（HR 1.66；CI 1.28 - 2.16）在多因素Cox回归分析中与疗效结局相关。年龄（HR 1.07；CI 1.05 - 1.09）和左心室肥厚（HR 1.94；CI 1.13 - 3.32）与安全性结局相关。