Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter.
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.
Singh
Bramah N
BN
Cardiology Division, Veterans Affairs Greater Los Angeles Healthcare System and the David Geffen School of Medicine at UCLA, Los Angeles, CA 90073, USA. bsingh@ucla.edu
Connolly
Stuart J
SJ
Crijns
Harry J G M
HJ
Roy
Denis
D
Kowey
Peter R
PR
Capucci
Alessandro
A
Radzik
David
D
Aliot
Etienne M
EM
Hohnloser
Stefan H
SH
D000368:Aged; D000638:Amiodarone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D001282:Atrial Flutter / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D004311:Double-Blind Method; D000077764:Dronedarone; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D055502:Secondary Prevention; D013997:Time Factors