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.