Celivarone for maintenance of sinus rhythm and conversion of atrial fibrillation/flutter

J Cardiovasc Electrophysiol. 2012 May;23(5):462-72. doi: 10.1111/j.1540-8167.2011.02234.x. Epub 2011 Dec 15.

Abstract

Introduction: Celivarone, a new noniodinated benzofuran derivative pharmacologically related to dronedarone and amiodarone, has been shown to have antiarrhythmic properties at a molecular level. The purpose of the 2 trials presented here (MAIA and CORYFEE) was to assess celivarone efficacy in the maintenance of sinus rhythm postcardioversion and for the conversion of atrial fibrillation (AF)/atrial flutter (AFL).

Methods and results: In the MAIA trial, 673 patients with AF/AFL recently converted to sinus rhythm were randomly assigned to receive 50, 100, 200, or 300 mg once-daily dosing of celivarone; 200 mg daily of amiodarone preceded by a loading dose of 600 mg for 10 days; or placebo. At 3 months' follow up, no significant difference was observed in time to AF/AFL relapse among the various celivarone groups and placebo. However, fewer symptomatic AF/AFL recurrences were observed in the lower-dose celivarone groups (26.6% for celivarone 50 mg [P = 0.022] and 25.2% for celivarone 100 mg [P = 0.018] vs 40.5% for placebo at 90 days). Fewer adverse events were observed with the use of celivarone and placebo than amiodarone. In the CORYFEE study, 150 patients with AF/AFL were randomly assigned to once-daily celivarone dosing of 300 or 600 mg, or placebo, for a 2-day treatment period. There was no significant difference in the rate of spontaneous conversion to sinus rhythm between the treatment and control groups.

Conclusions: In these studies, celivarone does not appear to be efficacious in the maintenance of sinus rhythm in AF/AFL patients or for the conversion of AF/AFL patients.

Trial registration: ClinicalTrials.gov NCT00232310 NCT00233441.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Arrhythmia Agents / administration & dosage
  • Anti-Arrhythmia Agents / adverse effects
  • Anti-Arrhythmia Agents / pharmacokinetics
  • Anti-Arrhythmia Agents / therapeutic use*
  • Atrial Fibrillation / diagnosis
  • Atrial Fibrillation / drug therapy*
  • Atrial Fibrillation / physiopathology
  • Atrial Flutter / diagnosis
  • Atrial Flutter / drug therapy*
  • Atrial Flutter / physiopathology
  • Benzofurans / administration & dosage
  • Benzofurans / adverse effects
  • Benzofurans / pharmacokinetics
  • Benzofurans / therapeutic use*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Electrocardiography
  • Female
  • Heart Conduction System / drug effects*
  • Heart Conduction System / physiopathology
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Recurrence
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome

Substances

  • Anti-Arrhythmia Agents
  • Benzofurans
  • celivarone

Associated data

  • ClinicalTrials.gov/NCT00232310
  • ClinicalTrials.gov/NCT00233441