title: Placebo-controlled, randomized clinical trial of azimilide for prevention of ventricular tachyarrhythmias in patients with an implantable cardioverter defibrillator.
abstract: 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.
  
  
  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.
authors.affiliation: Division of Cardiology, St. Michael's Hospital, 30 Bond St, Toronto, Ontario M5B 1W8, Canada. dorianp@smh.toronto.on.ca
authors.forename: Paul
authors.initials: P
authors.lastname: Dorian
authors.forename: Martin
authors.initials: M
authors.lastname: Borggrefe
authors.forename: Hussein R
authors.initials: HR
authors.lastname: Al-Khalidi
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Hohnloser
authors.forename: Jose M
authors.initials: JM
authors.lastname: Brum
authors.forename: Daljit S
authors.initials: DS
authors.lastname: Tatla
authors.forename: Johannes
authors.initials: J
authors.lastname: Brachmann
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Myerburg
authors.forename: David S
authors.initials: DS
authors.lastname: Cannom
authors.forename: Michael
authors.initials: M
authors.lastname: van der Laan
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Holroyde
authors.forename: Igor
authors.initials: I
authors.lastname: Singer
authors.forename: Craig M
authors.initials: CM
authors.lastname: Pratt
mesh_terms: D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017147:Defibrillators, Implantable; D004311:Double-Blind Method; D004554:Electric Countershock; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D006827:Hydantoins; D048289:Imidazolidines / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D055502:Secondary Prevention; D017180:Tachycardia, Ventricular / Q000517:prevention & control* / Q000628:therapy
chemical_list: D000889:Anti-Arrhythmia Agents; D006827:Hydantoins; D048289:Imidazolidines; D010879:Piperazines; C086123:azimilide