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

• Published in: The American heart journal Vol. 143; no. 4; pp. 643 - 649
• Main Authors: Page, Richard L., Connolly, Stuart J., Wilkinson, William E., Marcello, Stephen R., Schnell, Daniel J., Pritchett, Edward L.C.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.04.2002; Elsevier; Elsevier Limited
• Subjects: Adult; Aged; Anti-Arrhythmia Agents - adverse effects; Anti-Arrhythmia Agents - therapeutic use; Antiarythmic agents; Biological and medical sciences; Cardiovascular system; Double-Blind Method; Electrocardiography - drug effects; Female; Humans; Hydantoins; Imidazoles - adverse effects; Imidazoles - therapeutic use; Imidazolidines; Male; Medical sciences; Middle Aged; Patient Selection; Pharmacology. Drug treatments; Piperazines - adverse effects; Piperazines - therapeutic use; Tachycardia, Paroxysmal - drug therapy; Tachycardia, Supraventricular - drug therapy; Telemetry; Torsades de Pointes - etiology; Human; Arrhythmia; Treatment efficiency; Furan derivatives; Oral administration; Cardiovascular disease; Paroxysmal supraventricular tachycardia; Antiarrhythmic agent; Excitability disorder; Atrial flutter; Dose activity relation; Azimilide; Chemotherapy; Treatment; Heart disease; Classification; Clinical trial; Piperazine derivatives; Daily dose
• ISSN: 0002-8703; 1097-6744
• DOI: 10.1067/mhj.2002.120969

Background Azimilide is a novel classification III antiarrhythmic agent that blocks both I Krand I Ksand 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. (Am Heart J 2002;143:643-9.)