Four RCTs that compared dronedarone against placebo (n=6,007 patients) and four RCTs that compared amiodarone against placebo (n=664 patients) were included in the review. Seven were double-blind RCTs and one RCT was single-blinded. All but one RCT were considered to be 'good' quality. A ninth RCT directly comparing amiodarone with dronedarone was discussed but not included in the pooled analyses.
Compared against placebo, amiodarone was associated with a significant reduction in recurrent atrial fibrillation (OR 0.12, 95% CI 0.08 to 0.19), but dronedarone was not. Neither drug was associated with a significant reduction in all-cause mortality relative to placebo, but both drugs were associated with a significant increase in adverse events requiring withdrawal (OR 1.17, 95% CI 1.36 to 2.02 for dronedarone; OR 11.04, 95% CI 1.89 to 64.5 for amiodarone).
The indirect meta-analysis suggested that amiodarone was associated with a significantly greater reduction in atrial fibrillation recurrence than dronedarone (OR 0.16, 95% CI 0.06 to 0.42), but also a significantly greater risk of adverse events leading to withdrawal (OR 6.65, 95% CI 1.13 to 39.3). These results were supported by the findings of the logistic regression analysis and the results of the direct amiodarone-dronedarone comparison trial.