Placebo-Controlled, Randomized Clinical Trial of Azimilide for Prevention of Ventricular Tachyarrhythmias in Patients With an Implantable Cardioverter Defibrillator

Background—Although implanted cardioverter defibrillators (ICDs) effectively treat sustained ventricular tachyarrhythmias, up to 50% of ICD recipients eventually require concomitant antiarrhythmic drug therapy to prevent symptomatic arrhythmia recurrences and hence reduce the number of device therapies. Methods and Results—A total of 633 ICD recipients were enrolled in a randomized, double-blind, placebo-controlled study to evaluate the effect of daily doses of 75 or 125 mg of azimilide on recurrent symptomatic ventricular tachyarrhythmias and ICD therapies. Total all-cause shocks plus symptomatic ventricular tachycardia (VT) terminated by antitachycardia pacing (ATP) were significantly reduced by azimilide, with relative risk reductions of 57% (hazard ratio [HR]=0.43, 95% CI 0.26 to 0.69, P=0.0006) and 47% (HR=0.53, 95% CI 0.34 to 0.83, P=0.0053) at 75- and 125-mg doses, respectively. The reductions in all-cause shocks with both doses of azimilide did not achieve statistical significance. The incidence of all appropriate ICD therapies (shocks or ATP-terminated VT) was reduced significantly among patients taking 75 mg of azimilide (HR=0.52, 95% CI 0.30 to 0.89, P=0.017) and those taking 125 mg of azimilide (HR=0.38, 95% CI 0.22 to 0.65, P=0.0004). Five patients in the azimilide groups and 1 patient in the placebo group had torsade de pointes; all were successfully treated by the device. One patient taking 75 mg of azimilide had severe but reversible neutropenia. Conclusions—Azimilide significantly reduced the recurrence of VT or ventricular fibrillation terminated by shocks or ATP in ICD patients, thereby reducing the burden of symptomatic ventricular tachyarrhythmia.