Cumulative Experience of Azimilide-Associated Torsades de Pointes Ventricular Tachycardia in the 19 Clinical Studies Comprising the Azimilide Database

Craig M. Pratt, Hussein R. Al-Khalidi, Jose M. Brum, Michael J. Holroyde, Peter J. Schwartz, Stephen R. Marcello, Martin Borggrefe, Paul Dorian, A. John Camm

Research output: Contribution to journalArticle

Abstract

Objectives: The purpose of this study was to assess the incidence, temporal characteristics, and risk factors associated with azimilide-associated torsades de pointes (TdP) ventricular tachycardia. Background: Azimilide dihydrochloride is a class III antiarrhythmic drug possessing Ikr and Iks channel-blocking properties. Methods: Oral azimilide (75 to 125 mg/day) was taken by 5,375 patients in 19 clinical trials conducted at 775 international centers. Of 3,964 patients in double-blind studies, 1,427 had a history of atrial fibrillation or other supraventricular arrhythmia, 510 had an implantable cardioverter-defibrillator, and 2,027 were post-myocardial infarction patients with a left ventricular ejection fraction ≤35%. Results: The TdP occurred in 56 patients assigned to azimilide, was dose-related, and tended to occur earlier with an azimilide-loading regimen. Forty-three percent of TdP patients had a QT interval corrected by Bazett's formula, for heart rate, (QTc) ≥500 ms at the time of or before the TdP occurrence. Significant risk factors using logistic regression were increasing age, female gender, diuretic use, and lack of aspirin use. Conclusions: Azimilide-associated TdP has characteristics and risk factors similar to other Ikr blockers. However, there is a distinctive temporal profile. The TdP events are not concentrated in the first week. The azimilide-associated TdP rate is 1% (95% confidence interval 0.78 to 1.35) and is not increased in patients with low left ventricular ejection fraction, even in women.

Original languageEnglish
Pages (from-to)471-477
Number of pages7
JournalJournal of the American College of Cardiology
Volume48
Issue number3
DOIs
Publication statusPublished - Aug 1 2006

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Torsades de Pointes
Ventricular Tachycardia
Databases
Stroke Volume
Implantable Defibrillators
Anti-Arrhythmia Agents
azimilide
Clinical Studies
Double-Blind Method
Diuretics
Atrial Fibrillation
Aspirin
Cardiac Arrhythmias
Heart Rate
Logistic Models
Myocardial Infarction
Clinical Trials
Confidence Intervals
Incidence

ASJC Scopus subject areas

  • Nursing(all)

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Cumulative Experience of Azimilide-Associated Torsades de Pointes Ventricular Tachycardia in the 19 Clinical Studies Comprising the Azimilide Database. / Pratt, Craig M.; Al-Khalidi, Hussein R.; Brum, Jose M.; Holroyde, Michael J.; Schwartz, Peter J.; Marcello, Stephen R.; Borggrefe, Martin; Dorian, Paul; Camm, A. John.

In: Journal of the American College of Cardiology, Vol. 48, No. 3, 01.08.2006, p. 471-477.

Research output: Contribution to journalArticle

Pratt, Craig M. ; Al-Khalidi, Hussein R. ; Brum, Jose M. ; Holroyde, Michael J. ; Schwartz, Peter J. ; Marcello, Stephen R. ; Borggrefe, Martin ; Dorian, Paul ; Camm, A. John. / Cumulative Experience of Azimilide-Associated Torsades de Pointes Ventricular Tachycardia in the 19 Clinical Studies Comprising the Azimilide Database. In: Journal of the American College of Cardiology. 2006 ; Vol. 48, No. 3. pp. 471-477.
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abstract = "Objectives: The purpose of this study was to assess the incidence, temporal characteristics, and risk factors associated with azimilide-associated torsades de pointes (TdP) ventricular tachycardia. Background: Azimilide dihydrochloride is a class III antiarrhythmic drug possessing Ikr and Iks channel-blocking properties. Methods: Oral azimilide (75 to 125 mg/day) was taken by 5,375 patients in 19 clinical trials conducted at 775 international centers. Of 3,964 patients in double-blind studies, 1,427 had a history of atrial fibrillation or other supraventricular arrhythmia, 510 had an implantable cardioverter-defibrillator, and 2,027 were post-myocardial infarction patients with a left ventricular ejection fraction ≤35{\%}. Results: The TdP occurred in 56 patients assigned to azimilide, was dose-related, and tended to occur earlier with an azimilide-loading regimen. Forty-three percent of TdP patients had a QT interval corrected by Bazett's formula, for heart rate, (QTc) ≥500 ms at the time of or before the TdP occurrence. Significant risk factors using logistic regression were increasing age, female gender, diuretic use, and lack of aspirin use. Conclusions: Azimilide-associated TdP has characteristics and risk factors similar to other Ikr blockers. However, there is a distinctive temporal profile. The TdP events are not concentrated in the first week. The azimilide-associated TdP rate is 1{\%} (95{\%} confidence interval 0.78 to 1.35) and is not increased in patients with low left ventricular ejection fraction, even in women.",
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AU - Al-Khalidi, Hussein R.

AU - Brum, Jose M.

AU - Holroyde, Michael J.

AU - Schwartz, Peter J.

AU - Marcello, Stephen R.

AU - Borggrefe, Martin

AU - Dorian, Paul

AU - Camm, A. John

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N2 - Objectives: The purpose of this study was to assess the incidence, temporal characteristics, and risk factors associated with azimilide-associated torsades de pointes (TdP) ventricular tachycardia. Background: Azimilide dihydrochloride is a class III antiarrhythmic drug possessing Ikr and Iks channel-blocking properties. Methods: Oral azimilide (75 to 125 mg/day) was taken by 5,375 patients in 19 clinical trials conducted at 775 international centers. Of 3,964 patients in double-blind studies, 1,427 had a history of atrial fibrillation or other supraventricular arrhythmia, 510 had an implantable cardioverter-defibrillator, and 2,027 were post-myocardial infarction patients with a left ventricular ejection fraction ≤35%. Results: The TdP occurred in 56 patients assigned to azimilide, was dose-related, and tended to occur earlier with an azimilide-loading regimen. Forty-three percent of TdP patients had a QT interval corrected by Bazett's formula, for heart rate, (QTc) ≥500 ms at the time of or before the TdP occurrence. Significant risk factors using logistic regression were increasing age, female gender, diuretic use, and lack of aspirin use. Conclusions: Azimilide-associated TdP has characteristics and risk factors similar to other Ikr blockers. However, there is a distinctive temporal profile. The TdP events are not concentrated in the first week. The azimilide-associated TdP rate is 1% (95% confidence interval 0.78 to 1.35) and is not increased in patients with low left ventricular ejection fraction, even in women.

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