title: 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.
abstract: OBJECTIVE
  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.
authors: Sidney Kimmel Medical College, Thomas Jefferson University, 214 N. Ithan Ave, Villanova, PA, USA, michael.ezekowitz@comcast.net.
authors: Michael D
authors: MD
authors: Ezekowitz
authors: Kenneth A
authors: KA
authors: Ellenbogen
authors: John P
authors: JP
authors: DiMarco
authors: Karoly
authors: K
authors: Kaszala
authors: Alexander
authors: A
authors: Boddy
authors: Gregory P
authors: GP
authors: Geba
authors: Gregory Geba
authors: GG
authors: P
authors: Andrew
authors: A
authors: Koren
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000638:Amiodarone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000628:therapy; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D000077764:Dronedarone; D004334:Drug Administration Schedule; D004562:Electrocardiography / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008991:Monitoring, Physiologic; D010138:Pacemaker, Artificial; D012016:Reference Values; D018570:Risk Assessment; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000889:Anti-Arrhythmia Agents; D000077764:Dronedarone; D000638:Amiodarone
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