Antiarrhythmic effects of aximilide in paroxysmal supraventricular tachycardia: Efficacy and dose-response

Background Azimilide is a novel classification III antiarrhythmic agent that blocks both I-Kr, and I-Ks, and shows evidence of efficacy in patients with atrial fibrillation or flutter, Its effect on paroxysmal supraventricular tachycardia (PSVT) has not been reported. Methods and Results One hundred ninety-three patients with symptomatic PSVT were enrolled in 4 double-blind, randomized, placebo-controlled clinical trials with almost identical trial design (supraventricular arrhythmia-1 [SVA-1], SVA-2, SVA-3, and SVA-4), performed as a separate stratum of studies that also included a stratum of patients with atrial fibrillation or flutter. Patients received oral azimilide (100 mg in SVA-1 and SVA-3, 35 or 75 mg in SVA-2, and 125 mg in SVA-4) or matching placebo twice daily for 3 days (loading period), followed by once-daily dosing (maintenance period). The primary outcome variable was the first recording of a symptomatic supraventricular arrhythmia (either PSVT, atrial fibrillation, or atrial flutter) recorded on a transtelephonic electrocardiographic event recorder. The duration of study was 270 days in SVA-1 and SVA-2 and 180 days in SVA-3 and SVA-4. Combined analysis results of the PSVT stratum from the 4 studies showed a dose-response relationship in prolongation of time to recurrence (P=.02). In the combined 100-mg daily dose, the hazard ratio (placebo:azimilide) was 2.35 (P=.023). The hazard ratio for the 125-mg daily dose measured 1.28 (P=not significant). However, the time to recurrence was prolonged when the patients receiving 100 and 125 mg daily were combined and compared with placebo (P=.02). There were no deaths and 1 case of torsades de pointes. Conclusion These trial results suggest a significant dose-related suppression of PSVT with azimilide, with a low risk of serious adverse events.