Antiarrhythmic effects of azimilide 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.


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.


CONCLUSIONS
These trial results suggest a significant dose-related suppression of PSVT with azimilide, with a low risk of serious adverse events.
Page
Richard L
RL
Department of Medicine, Cardiovascular Division, University of Texas Southwestern Medical Center, Parkland Memorial Hospital, Dallas, Tex 75390-9047, USA. rpage@parknet.pmh.org
Connolly
Stuart J
SJ
Wilkinson
William E
WE
Marcello
Stephen R
SR
Schnell
Daniel J
DJ
Pritchett
Edward L C
EL
D000328:Adult; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006801:Humans; D006827:Hydantoins; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D048289:Imidazolidines; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D013614:Tachycardia, Paroxysmal / Q000188:drug therapy*; D013617:Tachycardia, Supraventricular / Q000188:drug therapy*; D013686:Telemetry; D016171:Torsades de Pointes / Q000209:etiology
D000889:Anti-Arrhythmia Agents; D006827:Hydantoins; D007093:Imidazoles; D048289:Imidazolidines; D010879:Piperazines; C086123:azimilide