Dronedarone for prevention of atrial fibrillation: A dose-ranging study

被引:260
作者
Touboul, P
Brugada, J
Capucci, A
Crijns, HJGM
Edvardsson, N
Hohnloser, SH
机构
[1] Hop Cardiol, Div Cardiol, Lyon, France
[2] Univ Barcelona, Hosp Clin, Cardiovasc Inst, Arrhythmia Unit, Barcelona, Spain
[3] Osped Civile Polichirurg, Div Cardiol, I-29100 Piacenza, Italy
[4] Univ Limburg, Acad Hosp Maastricht, Dept Cardiol, Maastricht, Netherlands
[5] Univ Limburg, Cardiovasc Res Inst, NL-6200 MD Maastricht, Netherlands
[6] Sahlgrens Univ Hosp, Div Cardiol, S-41345 Gothenburg, Sweden
[7] Univ Frankfurt, Dept Cardiol, D-6000 Frankfurt, Germany
关键词
antiarrhythmic agents; atrial fibrillation; cardioversion;
D O I
10.1016/S0195-668X(03)00321-X
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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, 1600 mg 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 800 mg, 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 1600 mg group. Premature drug discontinuations affected 22.6% of subjects given 1600 mg dronedarone versus 3.9% on 800 mg and were mainly due to gastrointestinal side effects. No evidence of thyroid, ocular or pulmonary toxicity was found. Conclusion Dronedarone, at a 800 mg 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. (C) 2003 Published by Elsevier Ltd on behalf of The European Society of Cardiology.
引用
收藏
页码:1481 / 1487
页数:7
相关论文
共 24 条
[1]   TESTS FOR LINEAR TRENDS IN PROPORTIONS AND FREQUENCIES [J].
ARMITAGE, P .
BIOMETRICS, 1955, 11 (03) :375-386
[2]  
BIALY D, 1992, J AM COLL CARDIOL, V19, P41
[3]  
Chun SH, 1988, ACTA MED SCAND, V223, P53
[4]   EFFICACY AND SAFETY OF QUINIDINE THERAPY FOR MAINTENANCE OF SINUS RHYTHM AFTER CARDIOVERSION - A METAANALYSIS OF RANDOMIZED CONTROL TRIALS [J].
COPLEN, SE ;
ANTMAN, EM ;
BERLIN, JA ;
HEWITT, P ;
CHALMERS, TC .
CIRCULATION, 1990, 82 (04) :1106-1116
[5]  
COSNIERPUCHEU S, 2001, ARCH MAL COEUR VAISS, V94, P364
[6]  
COX DR, 1972, J R STAT SOC B, V34, P187
[7]   EFFECTS OF A NEW AMIODARONE-LIKE AGENT, SR-33589, IN COMPARISON TO AMIODARONE, D,L-SOTALOL, AND LIGNOCAINE, ON ISCHEMIA-INDUCED VENTRICULAR ARRHYTHMIAS IN ANESTHETIZED PIGS [J].
FINANCE, O ;
MANNING, A ;
CHATELAIN, P .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1995, 26 (04) :570-576
[8]   SR-33589, A NEW AMIODARONE-LIKE ANTIARRHYTHMIC AGENT - ANTI-ADRENOCEPTOR ACTIVITY IN ANESTHETIZED AND CONSCIOUS DOGS [J].
HODEIGE, D ;
HEYNDRICKX, JP ;
CHATELAIN, P ;
MANNING, A .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1995, 279 (01) :25-32
[9]   Rhythm or rate control in atrial fibrillation - Pharmacological intervention in atrial fibrillation (PIAF): a randomised trial [J].
Hohnloser, SH ;
Kuck, KH ;
Lilienthal, J .
LANCET, 2000, 356 (9244) :1789-1794
[10]   PROARRHYTHMIA WITH CLASS-III ANTIARRHYTHMIC DRUGS - DEFINITION, ELECTROPHYSIOLOGIC MECHANISMS, INCIDENCE, PREDISPOSING FACTORS, AND CLINICAL IMPLICATIONS [J].
HOHNLOSER, SH ;
SINGH, BN .
JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, 1995, 6 (10) :920-936