NEW YORK (Reuters Health) – In patients with atrial fibrillation (AF), the antiarrhythmic dronedarone is less effective than amiodarone at maintaining sinus rhythm, but it has fewer adverse effects, researchers report in the Journal of the American College of Cardiology for September 15.

“Dronedarone is an important, and much needed addition to the antiarrhythmic armamentarium,” lead author Dr. Jonathan P. Piccini noted in an email to Reuters Health.

“Based upon the results of the landmark ATHENA trial, dronedarone is approved for the reduction of cardiovascular hospitalization risk in patients with atrial fibrillation and risk factors for stroke,” he added.

But while there’s a wealth of trial data comparing dronedarone to placebo, there is much less information on dronedarone compared to other antiarrhythmic agents, Dr. Piccini explained.

He and his co-authors, all from Duke University in Durham, North Carolina, note in their report that dronedarone is a noniodinated benzofuran similar to amiodarone.

Using indirect comparison meta-analysis and the available head-to-head clinical trial data, the investigators focused on four placebo-controlled trials of dronedarone, four placebo-controlled trials of amiodarone, and one trial of dronedarone versus amiodarone.

“Although dronedarone may prolong time to recurrent AF early on, long-term maintenance of sinus rhythm appears disappointing,” Dr. Piccini and colleagues wrote.

Random-effects modeling showed a significant estimated reduction in recurrent AF with amiodarone versus placebo (odds ratio, 0.12) but not dronedarone versus placebo (odds ratio, 0.79), the investigators report.

A normal logistic regression model incorporating all trial evidence showed that patients treated with amiodarone were twice as likely as patients treated with dronedarone to remain in sinus rhythm (odds ratio, 0.49, for recurrent AF; p < 0.001). However, amiodarone was associated with a trend toward greater death from any cause (odds ratio 1.61; p = 0.066) and was associated with greater rates of adverse events leading to discontinuation of treatment (odds ratio 1.81; p < 0.001). The research team estimated that for every 1,000 patients treated with dronedarone instead of amiodarone, there would be approximately 228 more recurrences of AF in exchange for 9.6 fewer deaths and 62 fewer adverse events requiring discontinuation of drug. “More long-term data are needed to refine these estimates and to define the optimum balance of efficacy and toxicity for patients with AF,” they conclude. In an accompanying editorial, Dr. Paul S. Chan of the University of Missouri in Kansas City, Missouri and colleagues make the point that indirect meta-analysis has “significant limitations beyond those associated with meta-analyses in general.” Until direct comparisons are done in adequately powered clinical trials, the editorialists say, “clinicians will need to balance whether the use of dronedarone, a less efficacious but possibly safer antiarrhythmic drug than amiodarone (in patients without reduced ejection fraction), is justified for their patients with AF.” Reference:
J Am Coll Cardiol 2009;54:1089-1095,1096-1098.