A placebo-controlled, double-blind, randomized, multicenter study to assess the effects of dronedarone 400 mg twice daily for 12 weeks on atrial fibrillation burden in subjects with permanent pacemakers

• Published in: Journal of interventional cardiac electrophysiology Vol. 42; no. 2; pp. 69 - 76
• Main Authors: Ezekowitz, Michael D., Ellenbogen, Kenneth A., DiMarco, John P., Kaszala, Karoly, Boddy, Alexander, P., Gregory Geba, Koren, Andrew
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.03.2015; Springer Nature B.V
• Subjects: Aged; Aged, 80 and over; Amiodarone - administration & dosage; Amiodarone - adverse effects; Amiodarone - analogs & derivatives; Anti-Arrhythmia Agents - administration & dosage; Anti-Arrhythmia Agents - adverse effects; Atrial Fibrillation - drug therapy; Atrial Fibrillation - therapy; Cardiology; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Electrocardiography - methods; Female; Follow-Up Studies; Humans; Male; Medicine; Medicine & Public Health; Monitoring, Physiologic; Pacemaker, Artificial; Reference Values; Risk Assessment; Time Factors; Treatment Outcome; Burden; Pacemaker; Atrial fibrillation; Dronedarone
• ISSN: 1383-875X; 1572-8595; 1572-8595
• DOI: 10.1007/s10840-014-9966-z

Purpose Dronedarone is a benzofuran derivative with a pharmacological profile similar to amiodarone but has a more rapid onset of action and a much shorter half-life (13–19 h). Our goal was to evaluate the efficacy of dronedarone in atrial fibrillation (AF) patients using dual-chamber pacemakers capable of quantifying atrial fibrillation burden. Methods Pacemakers were adjusted to optimize AF detection. Patients with AF burden > 1 % were randomized to dronedarone 400 mg twice daily (BID) or placebo. Pacemakers were interrogated after 4 and 12 weeks of treatment. The primary endpoint was the change in AF burden from baseline over the 12-week treatment period. Patients with permanent AF, severe/recently decompensated heart failure, and current use of antiarrhythmic drugs were excluded. AF burden was assessed by a core laboratory blinded to treatment assignment. Results From 285 patients screened, 112 were randomized (mean age 76 years, 60 % male, 84 % hypertensive, 65 % with sick sinus syndrome, 26 % with diabetes mellitus type II, 15 % with heart failure). Baseline mean (SEM) AF burden was 8.77 % (0.16) for placebo and 10.14 % (0.17) for dronedarone. Over the 12-week study period, AF burden compared to baseline decreased by 54.4 % (0.22) ( P  = 0.0009) with dronedarone and trended higher by 12.8 % (0.16) ( P  = 0.450) with placebo. The absolute change in burden was decreased by 5.5 % in the dronedarone group and increased by 1.1 % in the placebo group. Heart rate during AF was reduced to approximately 4 beats/min with dronedarone ( P  = 0.285). Adverse events were higher with dronedarone compared to placebo (65 vs 56 %). Conclusions Dronedarone reduced pacemaker-assessed the relative AF burden compared to baseline and placebo by over 50 % during the 12-week observation period.