Antiarrhythmic effects of azimilide in atrial fibrillation: Efficacy and dose-response

OBJECTIVES The purpose of this study was to assess the effectiveness of azi milide, a class III antiarrhythmic drug, in reducing the frequency of sympt omatic arrhythmia recurrences In patients with atrial fibrillation, atrial flutter or both. BACKGROUND Atrial fibrillation is an increasingly common disorder of the he art rhythm, and most patients with this problem are identified because they have symptoms associated with their arrhythmia. New antiarrhythmic therapi es are needed to treat patients with this problem. METHODS A total of 384 patients with a history of atrial fibrillation, atri al flutter or both were randomly assigned to receive once daily doses of pl acebo or azimilide; recurrent symptomatic arrhythmias were documented using transtelephonic electrocardiogram (ECC) recording. Azimilide 50 mg, 100 mg or 125 mg was tested; the primary efficacy analysis compared the time to f irst symptomatic recurrence in the combined azimilide 100 mg and 125 mg dos e groups with that in the placebo group using the log-rank test. RESULTS In the primary efficacy analysis, the time to first symptomatic arr hythmia recurrence was significantly prolonged in the combined azimilide 10 0 mg and 125 mg daily dose group compared with the placebo group (chi squar e 7.96, p = 0.005); the hazard ratio (placebo: azimilide) for this comparis on was 1.58 (95% confidence interval [CI] = 1.15, 2.16). In comparisons bet ween individual doses and placebo, the hazard ratio for the 50 mg daily dos e was 1.17 (95% CI = 0.83, 1.66; p = 0.37); for the 100 mg group, dose was 1.38 (95% CI = 0.96, 1.98; p = 0.08), and for the 125 mg group, dose was 1. 83 (95% CI = 1.24, 2.70; p = 0.002). CONCLUSIONS Azimilide significantly lengthened the symptomatic arrhythmia-f ree interval in patients with a history of atrial fibrillation, atrial flut ter or both. (C) 2000 by the American College of Cardiology.