A short-term, randomized, double-blind, parallel-group study to evaluate the efficacy and safety of dronedarone versus amiodarone in patients with persistent atrial fibrillation: the DIONYSOS study.
BACKGROUND
We compared the efficacy and safety of amiodarone and dronedarone in patients with persistent atrial fibrillation (AF).


METHODS
Five hundred and four amiodarone-naïve patients were randomized to receive dronedarone 400 mg bid (n = 249) or amiodarone 600 mg qd for 28 days then 200 mg qd (n = 255) for at least 6 months. Primary composite endpoint was recurrence of AF (including unsuccessful electrical cardioversion, no spontaneous conversion and no electrical cardioversion) or premature study discontinuation. Main safety endpoint (MSE) was occurrence of thyroid-, hepatic-, pulmonary-, neurologic-, skin-, eye-, or gastrointestinal-specific events, or premature study drug discontinuation following an adverse event.


RESULTS
Median treatment duration was 7 months. The primary composite endpoint was 75.1 and 58.8% with dronedarone and amiodarone, respectively, at 12 months (hazard ratio [HR] 1.59; 95% confidence interval [CI] 1.28-1.98; P < 0.0001), mainly driven by AF recurrence with dronedarone compared with amiodarone (63.5 vs 42.0%). AF recurrence after successful cardioversion was 36.5 and 24.3% with dronedarone and amiodarone, respectively. Premature drug discontinuation tended to be less frequent with dronedarone (10.4 vs 13.3%). MSE was 39.3 and 44.5% with dronedarone and amiodarone, respectively, at 12 months (HR = 0.80; 95% CI 0.60-1.07; P = 0.129), and mainly driven by fewer thyroid, neurologic, skin, and ocular events in the dronedarone group.


CONCLUSIONS
In this short-term study, dronedarone was less effective than amiodarone in decreasing AF recurrence, but had a better safety profile, specifically with regard to thyroid and neurologic events and a lack of interaction with oral anticoagulants.
Le Heuzey
Jean-Yves
JY
Cardiologie A et rythmologie, Hôpital Européen Georges Pompidou, Paris, France. jean-yves.le-heuzey@egp.aphp.fr
De Ferrari
Gaetano M
GM
Radzik
David
D
Santini
Massimo
M
Zhu
Junren
J
Davy
Jean-Marc
JM
D000368:Aged; D000638:Amiodarone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy*; D004311:Double-Blind Method; D000077764:Dronedarone; D004562:Electrocardiography / Q000187:drug effects; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000139:chemically induced; D018570:Risk Assessment; D013959:Thyroid Diseases / Q000139:chemically induced
D000889:Anti-Arrhythmia Agents; D000077764:Dronedarone; D000638:Amiodarone