2007/09/05 by Bramah N. Singh, Stuart J. Connolly, Harry J.G.M. Crijns +6 · 2 citations
Medicine · #Amiodarone #Anesthesia #Antiarrhythmic agent #Atrial Fibrillation Management and Outcomes #Atrial fibrillation #Atrial flutter #Cardiac Arrhythmias and Treatments #Cardiac electrophysiology and arrhythmias #Cardiology #Clinical endpoint #Dronedarone #Heart disease #Internal medicine #Medicine #Placebo #Randomized controlled trial #Sinus rhythm
paper · pdf · doi:10.1056/nejmoa054686
openalex publication_date 2007/09/05 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
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.