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An Amiodarone Cousin Is Modestly Effective

A new agent for maintenance of normal sinus rhythm in atrial fibrillation is effective but raises new questions.

Amiodarone is effective for maintaining sinus rhythm in patients with atrial fibrillation (AF), but it has substantial side effects and a very long half-life. Dronedarone, an antiarrhythmic agent pharmacologically similar to amiodarone, was developed with the aim of reducing side effects. In two industry-sponsored, randomized, controlled, double-blind trials conducted in 18 countries, researchers compared the efficacy of dronedarone and placebo for maintaining sinus rhythm in 1237 patients with AF. The primary endpoint was time from randomization to first documented recurrence of AF, and secondary endpoints were symptoms related to AF and heart rate during first recurrence.

At 12 months, 64% of the dronedarone group and 75% of the placebo group had experienced a recurrence (hazard ratio, 0.75). Median time to recurrence was 116 days in the dronedarone group and 53 days in the placebo group. Most first recurrences were symptomatic, and the pattern of symptoms did not differ between groups, except that heart rate was significantly lower in the dronedarone group than in the placebo group (mean, 103 vs. 117 beats per minute). Rates of pulmonary toxicity and of thyroid and liver dysfunction were not increased in the dronedarone group. However, the incidence of elevated serum creatinine was 12 times higher in the dronedarone group than in the placebo group (2.4% vs. 0.2%).

The authors caution that the results cannot be used to compare amiodarone and dronedarone and note that a prior trial of dronedarone in patients with heart failure was terminated early because of safety concerns (increased risk for death).

Comment: This study is one more band in the parade of studies that provide strong support for the concept that nothing comes without a cost. Would you trade a 10% decrease in recurrence of AF for a 1200% increase in renal dysfunction? Now, there is a survey worth doing.

— J. Stephen Bohan, MD, MS, FACP, FACEP

Published in Journal Watch Emergency Medicine October 5, 2007

Citation(s):

Singh BN et al. Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter. N Engl J Med 2007 Sep 6; 357:987.

• Original article (Subscription may be required)
• Medline abstract (Free)

Ezekowitz MD. Maintaining sinus rhythm — making treatment better than the disease. N Engl J Med 2007 Sep 6; 357:1039.

• Original article (Subscription may be required)
• Medline abstract (Free)