Efficacy and safety of celivarone, with amiodarone as calibrator, in patients with an implantable cardioverter-defibrillator for prevention of implantable cardioverter-defibrillator interventions or death

The ALPHEE study

ALPHEE Study Investigators

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background-: Celivarone is a new antiarrhythmic agent developed for the treatment of ventricular arrhythmias. This study investigated the efficacy and safety of celivarone in preventing implantable cardioverter-defibrillator (ICD) interventions or death. Methods and Results-: Celivarone (50, 100, or 300 mg/d) was assessed compared with placebo in this randomized, double-blind, placebo-controlled, parallel-group study. Amiodarone (200 mg/d after loading dose of 600 mg/d for 10 days) was used as a calibrator. A total of 486 patients with a left ventricular ejection fraction ≤40% and at least 1 ICD intervention for ventricular tachycardia or ventricular fibrillation in the previous month or ICD implantation in the previous month for documented ventricular tachycardia/ventricular fibrillation were randomized. Median treatment duration was 9 months. The primary efficacy end point was occurrence of ventricular tachycardia/ventricular fibrillation-triggered ICD interventions (shocks or antitachycardia pacing) or sudden death. The proportion of patients experiencing an appropriate ICD intervention or sudden death was 61.5% in the placebo group; 67.0%, 58.8%, and 54.9% in the celivarone 50-, 100-, and 300-mg groups, respectively; and 45.3% in the amiodarone group. Hazard ratios versus placebo for the primary end point ranged from 0.860 for celivarone 300 mg to 1.199 for celivarone 50 mg. None of the comparisons versus placebo were statistically significant. Celivarone had an acceptable safety profile. CONCLUSIONS-: Celivarone was not effective for the prevention of ICD interventions or sudden death. Clinical Trial Registration-: http://www.clinicaltrials.gov. Unique identifier: NCT00993382.

Original languageEnglish (US)
Pages (from-to)2649-2660
Number of pages12
JournalCirculation
Volume124
Issue number24
DOIs
StatePublished - Dec 13 2011
Externally publishedYes

Fingerprint

Amiodarone
Implantable Defibrillators
Safety
Placebos
Ventricular Fibrillation
Ventricular Tachycardia
Sudden Death
celivarone
Stroke Volume
Cardiac Arrhythmias
Shock
Clinical Trials
Therapeutics

Keywords

  • celivarone
  • implanted cardioverter defibrillators
  • sudden death
  • ventricular arrhythmia

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

@article{68444502d3d7414c97dabee3daf3d0c0,
title = "Efficacy and safety of celivarone, with amiodarone as calibrator, in patients with an implantable cardioverter-defibrillator for prevention of implantable cardioverter-defibrillator interventions or death: The ALPHEE study",
abstract = "Background-: Celivarone is a new antiarrhythmic agent developed for the treatment of ventricular arrhythmias. This study investigated the efficacy and safety of celivarone in preventing implantable cardioverter-defibrillator (ICD) interventions or death. Methods and Results-: Celivarone (50, 100, or 300 mg/d) was assessed compared with placebo in this randomized, double-blind, placebo-controlled, parallel-group study. Amiodarone (200 mg/d after loading dose of 600 mg/d for 10 days) was used as a calibrator. A total of 486 patients with a left ventricular ejection fraction ≤40{\%} and at least 1 ICD intervention for ventricular tachycardia or ventricular fibrillation in the previous month or ICD implantation in the previous month for documented ventricular tachycardia/ventricular fibrillation were randomized. Median treatment duration was 9 months. The primary efficacy end point was occurrence of ventricular tachycardia/ventricular fibrillation-triggered ICD interventions (shocks or antitachycardia pacing) or sudden death. The proportion of patients experiencing an appropriate ICD intervention or sudden death was 61.5{\%} in the placebo group; 67.0{\%}, 58.8{\%}, and 54.9{\%} in the celivarone 50-, 100-, and 300-mg groups, respectively; and 45.3{\%} in the amiodarone group. Hazard ratios versus placebo for the primary end point ranged from 0.860 for celivarone 300 mg to 1.199 for celivarone 50 mg. None of the comparisons versus placebo were statistically significant. Celivarone had an acceptable safety profile. CONCLUSIONS-: Celivarone was not effective for the prevention of ICD interventions or sudden death. Clinical Trial Registration-: http://www.clinicaltrials.gov. Unique identifier: NCT00993382.",
keywords = "celivarone, implanted cardioverter defibrillators, sudden death, ventricular arrhythmia",
author = "{ALPHEE Study Investigators} and Kowey, {Peter R.} and Crijns, {Harry J.G.M.} and Aliot, {Etienne M.} and Alessandro Capucci and Piotr Kulakowski and David Radzik and Denis Roy and Connolly, {Stuart J.} and Hohnloser, {Stefan H.} and Singh, {B. M.} and J. Seltzer and Knight, {B. P.} and Kadish, {A. H.} and A. Smith and J. Blaauw and {Van Opstal}, J. and K. Vernooy and {Van Empel}, V. and {Smid-Ter Bekke}, R. and L. Guedon and C. Kouakam and N. Sadoul and H. Blangy and L. Freysz and P. Mabo and C. Leclercq and A. Giniger and G. Albina and V. Sammartino and I. Reyes and H. Manzolillo and R. Pantich and Ruveda, {S. M.} and Pozzer, {D. L.} and L. Aguinaga and G. Paterlini and H. Edouardo and L. Veronica and J. Hill and S. Yeshwant and S. Butterly and M. Indrajith and S. Cox and R. Perel and H. Finn and W. Heddle and C. Burdeniuk and C. Singleton and A. McGavigan and Eric Stecker",
year = "2011",
month = "12",
day = "13",
doi = "10.1161/CIRCULATIONAHA.111.072561",
language = "English (US)",
volume = "124",
pages = "2649--2660",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "24",

}

TY - JOUR

T1 - Efficacy and safety of celivarone, with amiodarone as calibrator, in patients with an implantable cardioverter-defibrillator for prevention of implantable cardioverter-defibrillator interventions or death

T2 - The ALPHEE study

AU - ALPHEE Study Investigators

AU - Kowey, Peter R.

AU - Crijns, Harry J.G.M.

AU - Aliot, Etienne M.

AU - Capucci, Alessandro

AU - Kulakowski, Piotr

AU - Radzik, David

AU - Roy, Denis

AU - Connolly, Stuart J.

AU - Hohnloser, Stefan H.

AU - Singh, B. M.

AU - Seltzer, J.

AU - Knight, B. P.

AU - Kadish, A. H.

AU - Smith, A.

AU - Blaauw, J.

AU - Van Opstal, J.

AU - Vernooy, K.

AU - Van Empel, V.

AU - Smid-Ter Bekke, R.

AU - Guedon, L.

AU - Kouakam, C.

AU - Sadoul, N.

AU - Blangy, H.

AU - Freysz, L.

AU - Mabo, P.

AU - Leclercq, C.

AU - Giniger, A.

AU - Albina, G.

AU - Sammartino, V.

AU - Reyes, I.

AU - Manzolillo, H.

AU - Pantich, R.

AU - Ruveda, S. M.

AU - Pozzer, D. L.

AU - Aguinaga, L.

AU - Paterlini, G.

AU - Edouardo, H.

AU - Veronica, L.

AU - Hill, J.

AU - Yeshwant, S.

AU - Butterly, S.

AU - Indrajith, M.

AU - Cox, S.

AU - Perel, R.

AU - Finn, H.

AU - Heddle, W.

AU - Burdeniuk, C.

AU - Singleton, C.

AU - McGavigan, A.

AU - Stecker, Eric

PY - 2011/12/13

Y1 - 2011/12/13

N2 - Background-: Celivarone is a new antiarrhythmic agent developed for the treatment of ventricular arrhythmias. This study investigated the efficacy and safety of celivarone in preventing implantable cardioverter-defibrillator (ICD) interventions or death. Methods and Results-: Celivarone (50, 100, or 300 mg/d) was assessed compared with placebo in this randomized, double-blind, placebo-controlled, parallel-group study. Amiodarone (200 mg/d after loading dose of 600 mg/d for 10 days) was used as a calibrator. A total of 486 patients with a left ventricular ejection fraction ≤40% and at least 1 ICD intervention for ventricular tachycardia or ventricular fibrillation in the previous month or ICD implantation in the previous month for documented ventricular tachycardia/ventricular fibrillation were randomized. Median treatment duration was 9 months. The primary efficacy end point was occurrence of ventricular tachycardia/ventricular fibrillation-triggered ICD interventions (shocks or antitachycardia pacing) or sudden death. The proportion of patients experiencing an appropriate ICD intervention or sudden death was 61.5% in the placebo group; 67.0%, 58.8%, and 54.9% in the celivarone 50-, 100-, and 300-mg groups, respectively; and 45.3% in the amiodarone group. Hazard ratios versus placebo for the primary end point ranged from 0.860 for celivarone 300 mg to 1.199 for celivarone 50 mg. None of the comparisons versus placebo were statistically significant. Celivarone had an acceptable safety profile. CONCLUSIONS-: Celivarone was not effective for the prevention of ICD interventions or sudden death. Clinical Trial Registration-: http://www.clinicaltrials.gov. Unique identifier: NCT00993382.

AB - Background-: Celivarone is a new antiarrhythmic agent developed for the treatment of ventricular arrhythmias. This study investigated the efficacy and safety of celivarone in preventing implantable cardioverter-defibrillator (ICD) interventions or death. Methods and Results-: Celivarone (50, 100, or 300 mg/d) was assessed compared with placebo in this randomized, double-blind, placebo-controlled, parallel-group study. Amiodarone (200 mg/d after loading dose of 600 mg/d for 10 days) was used as a calibrator. A total of 486 patients with a left ventricular ejection fraction ≤40% and at least 1 ICD intervention for ventricular tachycardia or ventricular fibrillation in the previous month or ICD implantation in the previous month for documented ventricular tachycardia/ventricular fibrillation were randomized. Median treatment duration was 9 months. The primary efficacy end point was occurrence of ventricular tachycardia/ventricular fibrillation-triggered ICD interventions (shocks or antitachycardia pacing) or sudden death. The proportion of patients experiencing an appropriate ICD intervention or sudden death was 61.5% in the placebo group; 67.0%, 58.8%, and 54.9% in the celivarone 50-, 100-, and 300-mg groups, respectively; and 45.3% in the amiodarone group. Hazard ratios versus placebo for the primary end point ranged from 0.860 for celivarone 300 mg to 1.199 for celivarone 50 mg. None of the comparisons versus placebo were statistically significant. Celivarone had an acceptable safety profile. CONCLUSIONS-: Celivarone was not effective for the prevention of ICD interventions or sudden death. Clinical Trial Registration-: http://www.clinicaltrials.gov. Unique identifier: NCT00993382.

KW - celivarone

KW - implanted cardioverter defibrillators

KW - sudden death

KW - ventricular arrhythmia

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U2 - 10.1161/CIRCULATIONAHA.111.072561

DO - 10.1161/CIRCULATIONAHA.111.072561

M3 - Article

VL - 124

SP - 2649

EP - 2660

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 24

ER -