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.
  
  
  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.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov. Unique identifier: NCT00993382.
authors.affiliation: Lankenau Hospital and Institute of Medical Research, Wynnewood, PA, USA. KoweyP@MLHS.ORG
authors.forename: Peter R
authors.initials: PR
authors.lastname: Kowey
authors.forename: Harry J G M
authors.initials: HJ
authors.lastname: Crijns
authors.forename: Etienne M
authors.initials: EM
authors.lastname: Aliot
authors.forename: Alessandro
authors.initials: A
authors.lastname: Capucci
authors.forename: Piotr
authors.initials: P
authors.lastname: Kulakowski
authors.forename: David
authors.initials: D
authors.lastname: Radzik
authors.forename: Denis
authors.initials: D
authors.lastname: Roy
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Connolly
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Hohnloser
mesh_terms: D000368:Aged; D000638:Amiodarone / Q000627:therapeutic use*; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001572:Benzofurans / Q000627:therapeutic use*; D016757:Death, Sudden, Cardiac / Q000453:epidemiology / Q000517:prevention & control*; D017147:Defibrillators, Implantable; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D017180:Tachycardia, Ventricular / Q000453:epidemiology / Q000517:prevention & control* / Q000628:therapy; D016896:Treatment Outcome; D014693:Ventricular Fibrillation / Q000453:epidemiology / Q000517:prevention & control* / Q000628:therapy
chemical_list: D000889:Anti-Arrhythmia Agents; D001572:Benzofurans; C499879:celivarone; D000638:Amiodarone