Placebo-controlled, randomized clinical trial of azimilide for prevention of ventricular tachyarrhythmias in patients with an implantable cardioverter defibrillator

Paul Dorian, Martin Borggrefe, Hussein R. Al-Khalidi, Stefan H. Hohnloser, Jose M. Brum, Daljit S. Tatla, Johannes Brachmann, Robert J Myerburg, David S. Cannom, Michael Van Der Laan, Michael J. Holroyde, Igor Singer, Craig M. Pratt

Research output: Contribution to journalArticle

131 Citations (Scopus)

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. 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.

Original languageEnglish
Pages (from-to)3646-3654
Number of pages9
JournalCirculation
Volume110
Issue number24
DOIs
StatePublished - Dec 14 2004

Fingerprint

Implantable Defibrillators
Tachycardia
Defibrillators
Randomized Controlled Trials
Placebos
Ventricular Tachycardia
Shock
Convulsive Therapy
Torsades de Pointes
Recurrence
Equipment and Supplies
azimilide
Anti-Arrhythmia Agents
Ventricular Fibrillation
Risk Reduction Behavior
Neutropenia
Cardiac Arrhythmias
Drug Therapy
Incidence
Therapeutics

Keywords

  • Antiarrhythmia agents
  • Cardioversion
  • Defibrillation
  • Drugs
  • Tachycardia

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Placebo-controlled, randomized clinical trial of azimilide for prevention of ventricular tachyarrhythmias in patients with an implantable cardioverter defibrillator. / Dorian, Paul; Borggrefe, Martin; Al-Khalidi, Hussein R.; Hohnloser, Stefan H.; Brum, Jose M.; Tatla, Daljit S.; Brachmann, Johannes; Myerburg, Robert J; Cannom, David S.; Van Der Laan, Michael; Holroyde, Michael J.; Singer, Igor; Pratt, Craig M.

In: Circulation, Vol. 110, No. 24, 14.12.2004, p. 3646-3654.

Research output: Contribution to journalArticle

Dorian, P, Borggrefe, M, Al-Khalidi, HR, Hohnloser, SH, Brum, JM, Tatla, DS, Brachmann, J, Myerburg, RJ, Cannom, DS, Van Der Laan, M, Holroyde, MJ, Singer, I & Pratt, CM 2004, 'Placebo-controlled, randomized clinical trial of azimilide for prevention of ventricular tachyarrhythmias in patients with an implantable cardioverter defibrillator', Circulation, vol. 110, no. 24, pp. 3646-3654. https://doi.org/10.1161/01.CIR.0000149240.98971.A8
Dorian, Paul ; Borggrefe, Martin ; Al-Khalidi, Hussein R. ; Hohnloser, Stefan H. ; Brum, Jose M. ; Tatla, Daljit S. ; Brachmann, Johannes ; Myerburg, Robert J ; Cannom, David S. ; Van Der Laan, Michael ; Holroyde, Michael J. ; Singer, Igor ; Pratt, Craig M. / Placebo-controlled, randomized clinical trial of azimilide for prevention of ventricular tachyarrhythmias in patients with an implantable cardioverter defibrillator. In: Circulation. 2004 ; Vol. 110, No. 24. pp. 3646-3654.
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AU - Dorian, Paul

AU - Borggrefe, Martin

AU - Al-Khalidi, Hussein R.

AU - Hohnloser, Stefan H.

AU - Brum, Jose M.

AU - Tatla, Daljit S.

AU - Brachmann, Johannes

AU - Myerburg, Robert J

AU - Cannom, David S.

AU - Van Der Laan, Michael

AU - Holroyde, Michael J.

AU - Singer, Igor

AU - Pratt, Craig M.

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N2 - 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.

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KW - Antiarrhythmia agents

KW - Cardioversion

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KW - Drugs

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