Dronedarone

Abstract

Abstract-Amiodarone is the most effective antiarrhythmic drug for maintaining sinus rhythm for patients with atrial fibrillation. Extra-cardiac side effects have been a limiting factor, especially during chronic use, and may offset its benefits. Dronedarone is a noniodinated benzofuran derivative of amiodarone that has been developed for the treatment of atrial fibrillation and atrial flutter. Similar to amiodarone, dronedarone is a potent blocker of multiple ion currents, including the rapidly activating delayed-rectifier potassium current, the slowly activating delayed-rectifier potassium current, the inward rectifier potassium current, the acetylcholine activated potassium current, peak sodium current, and L-type calcium current, and exhibits antiadrenergic effects. It has been studied for maintenance of sinus rhythm and control of ventricular response during episodes of atrial fibrillation. Dronedarone reduces mortality and morbidity in patients with high-risk atrial fibrillation, but may be unsafe in those with severe heart failure. This article will review evidence of safety and effectiveness of dronedarone in patients with atrial fibrillation. Key Words: amiodarone Ⅲ arrhythmia Ⅲ atrial fibrillations Ⅲ dronedarone A trial fibrillation (AF) is the most common arrhythmia in clinical practice and a usual cause for hospitalization and consultation. 1,2 It is an epidemic. It is projected that by 2050, more than 15 million people will contract AF in the United States alone. 2,3 Nearly 1 in every 10 persons aged 80 years and older has AF, 1,4,5 predisposing them to stroke, heart failure, and death. 6,7 A recent report from Centers for Medicare and Medicaid Services suggested that AF accounted for 1 765 304 hospitalizations in 1999. 8 The cost of medical care for patients with AF is almost 5 times higher than the care of patients without AF. 9,10 Despite improvements in primary and secondary prevention of ischemic heart disease and hypertension, the US age-adjusted death rate due to AF increased from 27.6 in 1980 to 69.8 per 100 000 in 1998. 2,11 Current therapy for AF is multidimensional and complicated. 12 There is some consensus on the benefits of anticoagulation in patients with AF, but debate continues about the relative value of rate versus rhythm control. Recent clinical trials have failed to demonstrate superiority of sinus rhythm maintenance, 13-18 but antiarrhythmic therapy is important for patients with severe symptoms. Conventional antiarrhythmic drugs have limited efficacy and safety. In fact, data suggest that the benefit of restoring and maintaining sinus rhythm in AF may be offset by significant cardiac and extracardiac side effects of currently used drugs. 19 -21 Improvement in the current approach to AF is clearly necessary. This review focuses on dronedarone, a new antiarrhythmic drug for AF suppression (Figure 1). Electrophysiological Properties of Dronedarone In Vitro ExperimentsIn vitro electrophysiological properties of dronedarone and its comparison with amiodarone are summarized in Table...

Dronedarone in patients with atrial fibrillation

“…These were more often observed at higher doses and required drug discontinuation in some patients. 10,11,15 Thyroid, ocular or pulmonary side effects in these studies were not significantly different from placebo-treated patients. Similar to amiodarone, dronedarone is associated with an increase in serum creatinine.…”

“…After oral administration steady state plasma levels are reached within four to eight days and the terminal half-life approximates 30 hours. 10 Similar to amiodarone, dronedarone is a multichannel blocking agent, affecting the rapid activating delayed-rectifier potassium current, the slowly activating delayed-rectifier potassium current, the inward rectifier potassium current, the acetylcholine activated potassium current, peak sodium current and the L-type calcium current. In addition, it exerts antiadrenergic effects.…”

“…In vitro studies comparing amiodarone and dronedarone have shown that dronedarone is a more potent blocker of peak sodium current, acetylcholine activated potassium current and that it also has stronger antiadrenergic effects. 10 An important difference with amiodarone is that it does not contain an iodine component and therefore lacks the iodine-related adverse effects.…”

“…10 Prolongation of the QT interval Experimental models show conflicting evidence regarding the effect of dronedarone on the QT-interval. In anaesthetised dogs with complete chronic AV block, acute administration of dronedarone reduced and homogenised repolarisation whereas chronic administration for four weeks increased the QTc interval.…”

“…10 At a mean follow-up period of seven months, amiodarone was more effective in maintaining sinus rhythm (44.7%) than dronedarone (26.1%). A recent meta-analysis including four placebo-controlled trials of dronedarone and four placebo-controlled trials of amiodarone also examined the efficacy of both dronedarone and amiodarone for prevention of AF recurrences.…”