Evaluation of the Switch From Amiodarone to Dronedarone in Patients With Atrial Fibrillation: Results of the ARTEMIS AF Studies

BACKGROUND: Switching between antiarrhythmic drugs is timed to minimize arrhythmia recurrence and adverse reactions. Dronedarone and amiodarone have similar electrophysiological profiles; however, little is known about the optimal timing of switching, given the long half-life of amiodarone. METHODS: The ARTEMIS atrial fibrillation (AF) Loading and Long-term studies evaluated switching patients with paroxysmal/persistent AF from amiodarone to dronedarone. Patients were randomized based on the timing of the switch: immediate, after a 2-week, or after a 4-week washout of amiodarone. Patients who did not convert to sinus rhythm after amiodarone loading underwent electrical cardioversion. The primary objectives were, for the Loading study, to evaluate recurrence of AF ≤60 days; and for the Long-term study, to profile the pharmacokinetics of dronedarone and its metabolite according to different timings of dronedarone initiation. RESULTS: In ARTEMIS AF Loading, 176 were randomized (planned 768) after a 28 ± 2 days load of oral amiodarone. Atrial fibrillation recurrence trended less in the immediate switch versus 4-week washout group (hazard ratio [HR] = 0.65 [97.5% CI: 0.34-1.23]; P = .14) and in the 2-week washout versus the 4-week washout group (HR = 0.75 [97.5% CI: 0.41-1.37]; P = .32). In ARTEMIS AF Long-term, 108 patients were randomized (planned 105). Pharmacokinetic analyses (n = 97) showed no significant differences for dronedarone/SR35021 exposures in the 3 groups. CONCLUSION: The trial was terminated early due to poor recruitment and so our findings are limited by low numbers. However, immediate switching from amiodarone to dronedarone appeared to be well tolerated and safe.