title: An individual patient-based meta-analysis of the effects of dronedarone in patients with atrial fibrillation.
abstract: OBJECTIVE
  Dronedarone is a non-iodinated benzofuran derivative with antiarrhythmic properties. In placebo-controlled atrial fibrillation (AF) trials, the drug was found to have divergent effects on endpoints such as cardiovascular death or hospitalization. The objective of this meta-analysis of all placebo-controlled studies was to provide insights on possible reasons for these divergent effects.
  
  
  RESULTS
  Individual data on 9664 patients were used from all AF placebo-controlled studies. The primary outcome measure was cardiovascular death. Cardiovascular hospitalization and hospitalization for heart failure were secondary endpoints. Predefined procedures were used to reduce inter-study heterogeneity adjusting for important baseline variables using a Cox model. Despite adjustments, a significant inter-trial heterogeneity of the outcome of cardiovascular mortality persisted (P-value of 0.005 for the treatment effect × study interaction). Further analyses were conducted in subgroups based on baseline clinical criteria: digoxin co-prescription, advanced heart failure, coronary artery disease, or the presence of permanent AF. These analyses allowed the calculation of a global treatment effect in two important patient subgroups, those with permanent AF in whom there was harm with respect to cardiovascular mortality [hazard ratio (HR) = 2.32; 95% confidence interval (CI) 1.13-4.75] and hospitalization for heart failure (HR = 1.674; 95% CI 1.05-2.67); and those with non-permanent AF in whom there was benefit in terms of cardiovascular hospitalization [HR = 0.751 95% CI (0.68-0.83)].
  
  
  CONCLUSIONS
  This meta-analysis demonstrates significant heterogeneity of dronedarone treatment effects across the placebo-controlled randomized trials. The most important predictor of a harmful effect of dronedarone on cardiovascular death and heart failure hospitalization was the presence of permanent AF.
authors.affiliation: Division of Clinical Electrophysiology, J. W. Goethe University, Theodor-Stern-Kai 7, D 60590 Frankfurt, Germany hohnloser@em.uni-frankfurt.de.
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Hohnloser
authors.affiliation: McMaster University, Hamilton, ON, Canada.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Connolly
authors.affiliation: Department of Clinical Sciences, St George's University of London, London UK.
authors.forename: A
authors.initials: A
authors.lastname: John Camm
authors.affiliation: The Cardiovascular Institute, Mount Sinai Medical Center, New York, NY, USA.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Halperin
authors.affiliation: Sanofi Recherche, Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Radzik
mesh_terms: D000638:Amiodarone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D000077764:Dronedarone; D006333:Heart Failure / Q000401:mortality / Q000503:physiopathology / Q000628:therapy; D006760:Hospitalization; D006801:Humans; D016016:Proportional Hazards Models; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000889:Anti-Arrhythmia Agents; D000077764:Dronedarone; D000638:Amiodarone
keywords: Atrial fibrillation; Dronedarone; Randomized clinical trials