Azimilide—CardiOversion MaintenancE Trial–II - A-COMET-II
The goal of the trial was to evaluate treatment with azimilide compared with placebo or sotalol on arrhythmia recurrence in patients with persistent atrial fibrillation (AF).
Patients Enrolled: 658
Mean Follow Up: 6 months
Mean Patient Age: Mean age 62 years
Age 18-80 years, documented (12-lead ECG) history of symptomatic AF lasting >48 hours and <6 months,="" adequate="" anticoagulant="" therapy,="" and="" planned="" electrical="" cardioversion="" months,="" adequate="" anticoagulant="" therapy,="" and="" planned="" electrical="">
Qualifying arrhythmias due to transient causes; history of syncope or angina pectoris precipitated by attacks of arrhythmia; history of torsade de pointes or other forms of polymorphic ventricular tachycardia or 2- or 3-degree atrioventricular block without a permanent pacemaker; recent myocardial infarction, unstable angina, or heart failure New York Heart Association class IV; family history of prolonged QT syndrome or with a baseline QTc >440 ms
First symptomatic or asymptomatic AF episode, flutter, or PSVT event for azimilide versus placebo
Primary endpoint comparing azimilide with sotalol
Patients were randomized to azimilide (125 mg per day; n = 211), sotalol (160 mg twice daily; n = 223), or placebo (n = 224). All patients were treated with study drug twice daily for the first 3 days. Patients not in sinus rhythm by day 4 underwent electrical cardioversion. If sinus was not restored, patients were withdrawn from the study.
At baseline, the majority of patients had been in AF for >27 days (73%). Structural heart disease was present in 73% of patients and 23% had a history of prior electrical conversion. Withdrawal due to unsuccessful cardioversion did not differ between groups (15% for azimilide, 12% for sotalol, 19% for placebo, p = 0.116). Completion of the 26-week study period was low in all groups, with the highest completion rate in the sotalol group (19% for azimilide, 33% for sotalol, 15% for placebo, p
The primary endpoint of arrhythmia recurrence occurred less frequently in the azimilide group compared with the placebo group (hazard ratio [HR], 1.29; p = 0.032), with a median time to recurrence of 12 days in the placebo group and 14 days in the azimilide group. Symptomatic events lasting >24 hours occurred in 23.2% of the azimilide group and 29% of the placebo group. Arrhythmia recurrence requiring hospitalization or cardioversion occurred less often in the azimilide group versus placebo (3.8% vs. 9.8%, p = 0.033).
For the comparison of azimilide versus sotalol, arrhythmia recurrence occurred less frequently in the sotalol group compared with the azimilide group (HR, 0.65; p = 0.0002), with a median time to recurrence of 14 days in the azimilide group and 28 days in the sotalol group. Symptomatic events lasting >24 hours occurred in 16.1% of the sotalol group and 23.2% of the azimilide group. Arrhythmia recurrence requiring hospitalization or cardioversion occurred in 3.1% of the sotalol group and 3.8% of the azimilide group. There were four deaths in the azimilide group, four in the sotalol group, and none in the placebo group. Withdrawal due to adverse events was higher in both the azimilide group (12.3%) and the sotalol group (13.9%) than in the placebo group (5.4%, p
Among patients with persistent AF who had converted to sinus rhythm, treatment with azimilide was associated with a reduction in the primary endpoint of AF, flutter, or paroxysmal supraventricular tachycardia (PSVT) event through 6 months compared with placebo, but sotalol was associated with a reduction in the endpoint compared with azimilide.
While azimilide was shown to be efficacious compared with placebo, the efficacy results with sotalol were better than with azimilide. Additionally, as with the A-COMET-I study, there were more cases of torsade de pointes in the azimilide group. Based on the inferior efficacy with azimilide compared with sotalol, but the increase in torsade de pointes, azimilide does not appear to be a treatment alternative for patients with persistent AF.
Lombardi F, Borggrefe M, Ruzyllo W, Luderitz B. Azimilide vs. placebo and sotalol for persistent atrial fibrillation: the A-COMET-II (Azimilide-CardiOversion MaintEnance Trial-II) trial. Eur Heart J 2006;27:2224–31.
Keywords: Tachycardia, Supraventricular, Imidazolidines, Electric Countershock, Piperazines, Sotalol, Electrocardiography, Torsades de Pointes
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