Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter

N Engl J Med. 2007 Sep 6;357(10):987-99. doi: 10.1056/NEJMoa054686.


Background: Amiodarone is effective in maintaining sinus rhythm in atrial fibrillation but is associated with potentially serious toxic effects. Dronedarone is a new antiarrhythmic agent pharmacologically related to amiodarone but developed to reduce the risk of side effects.

Methods: In two identical multicenter, double-blind, randomized trials, one conducted in Europe (ClinicalTrials.gov number, NCT00259428 [ClinicalTrials.gov] ) and one conducted in the United States, Canada, Australia, South Africa, and Argentina (termed the non-European trial, NCT00259376 [ClinicalTrials.gov] ), we evaluated the efficacy of dronedarone, with 828 patients receiving 400 mg of the drug twice daily and 409 patients receiving placebo. Rhythm was monitored transtelephonically on days 2, 3, and 5; at 3, 5, 7, and 10 months; during recurrence of arrhythmia; and at nine scheduled visits during a 12-month period. The primary end point was the time to the first recurrence of atrial fibrillation or flutter.

Results: In the European trial, the median times to the recurrence of arrhythmia were 41 days in the placebo group and 96 days in the dronedarone group (P=0.01). The corresponding durations in the non-European trial were 59 and 158 days (P=0.002). At the recurrence of arrhythmia in the European trial, the mean (+/-SD) ventricular rate was 117.5+/-29.1 beats per minute in the placebo group and 102.3+/-24.7 beats per minute in the dronedarone group (P<0.001); the corresponding rates in the non-European trial were 116.6+/-31.9 and 104.6+/-27.1 beats per minute (P<0.001). Rates of pulmonary toxic effects and of thyroid and liver dysfunction were not significantly increased in the dronedarone group.

Conclusions: Dronedarone was significantly more effective than placebo in maintaining sinus rhythm and in reducing the ventricular rate during recurrence of arrhythmia.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amiodarone / adverse effects
  • Amiodarone / analogs & derivatives*
  • Amiodarone / pharmacology
  • Amiodarone / therapeutic use
  • Anti-Arrhythmia Agents / adverse effects
  • Anti-Arrhythmia Agents / pharmacology
  • Anti-Arrhythmia Agents / therapeutic use*
  • Atrial Fibrillation / drug therapy*
  • Atrial Fibrillation / mortality
  • Atrial Fibrillation / physiopathology
  • Atrial Flutter / drug therapy*
  • Atrial Flutter / mortality
  • Atrial Flutter / physiopathology
  • Double-Blind Method
  • Dronedarone
  • Electrocardiography / drug effects
  • Female
  • Heart Rate / drug effects
  • Hospitalization / statistics & numerical data
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Secondary Prevention
  • Time Factors


  • Anti-Arrhythmia Agents
  • Dronedarone
  • Amiodarone

Associated data

  • ClinicalTrials.gov/NCT00259376
  • ClinicalTrials.gov/NCT00259428