Copyright © 2003 by the European Society of Cardiology.
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Dronedarone for prevention of atrial fibrillation: A dose-ranging study
a Division of Cardiology, Hôpital Cardiologique, Lyon, France
b Arrhythmia Unit, Cardiovascular Institute, Hospital Clinic, University of Barcelona, Barcelona, Spain
c Divisione di Cardiologia, Ospedale Civile Polichirurgico, Cantone del Cristo 29100 Piacenza, Italy
d Department of Cardiology, Academic Hospital Maastricht & Cardiovascular Research Institute, Maastricht, Netherlands
e Division of Cardiology, Sahlgrenska University Hospital, 413 45, Goteborg, Sweden
f J.W. Goethe University, Department of Cardiology, Frankfurt am Main, Germany
* Corresponding author. Stefan H Hohnloser, MD, Department of Medicine, Division of Cardiology, J W Goethe University, Theodor Stern-Kai 7, 60590 Frankfurt, Germany. Tel.: +49-69-6301-7321; fax: +49-69-6301-7017
E-mail address: Hohnloser{at}em.uni-frankfurt.de
Received 31 January 2002; revised 5 May 2003; accepted 12 June 2003
Aims Dronedarone, a benzofurane derivative without iodine substituents, shares the electrophysiologic properties of amiodarone. This study was designed to determine the most appropriate dose of dronedarone for prevention of atrial fibrillation (AF) after cardioversion.
Methods and results Patients with persistent AF were randomly allocated to 800, 1200, 1600mg daily doses of dronedarone or placebo. The main analysis was conducted on 199/270 patients, who entered the maintenance phase following pharmacological cardioversion or, if unsuccessful, DC cardioversion. Within 6-month follow-up, the time to AF relapse increased on dronedarone 800mg, with a median of 60 days vs 5.3 days in the placebo group (relative risk reduction 55% [95% CI, 28 to 72%] P=0.001). No significant effect was seen at higher doses. Spontaneous conversion to sinus rhythm on dronedarone occurred in 5.8 to 14.8% of patients (P=0.026). There were no proarrhythmic reactions. Drug-induced QT prolongation was only noticed in the 1600mg group. Premature drug discontinuations affected 22.6% of subjects given 1600mg dronedarone versus 3.9% on 800mg and were mainly due to gastrointestinal side effects. No evidence of thyroid, ocular or pulmonary toxicity was found.
Conclusion Dronedarone, at a 800mg daily dose, appears to be effective and safe for the prevention of AF relapses after cardioversion. The absence of thyroid side effects and of proarrhythmia are important features of the drug. Further studies are needed to better delineate the antiarrhythmic profile of the drug.
Key Words: Antiarrhythmic agents • Atrial fibrillation • Cardioversion
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