title: Mixed treatment comparison of dronedarone, amiodarone, sotalol, flecainide, and propafenone, for the management of atrial fibrillation.
abstract: OBJECTIVE
  Mixed treatment comparisons (MTC) were performed to assess the relative efficacy and tolerability of the main anti-arrhythmic drugs used for the treatment of atrial fibrillation (AF)/flutter.
  
  
  RESULTS
  Electronic databases were systematically searched to identify randomized controlled trials (RCTs) examining amiodarone, dronedarone, flecainide, propafenone, sotalol, or placebo for the treatment of AF. Thirty-nine RCTs met inclusion criteria and were combined using MTC models to provide direct and indirect comparisons in a single analysis. Results are presented vs. placebo. Amiodarone had the largest effect in reducing AF recurrence (OR 0.22, 95% CI 0.16-0.29). Amiodarone was associated with the highest rate of patients experiencing at least one serious adverse event (OR 2.41, 95% CI 0.96-6.06) and treatment withdrawals due to adverse events (OR 2.91, 95% CI 1.66-5.11). Dronedarone was associated with the lowest rate of proarrhythmic events including bradycardia (OR 1.45, 95% CI 1.02-2.08). Dronedarone significantly reduced the risk of stroke (OR 0.69, 95% CI 0.57-0.84). Trends towards increased mortality for sotalol (OR 3.44, 95% CI 1.02-11.59) and amiodarone (OR 2.17, 95% CI 0.63-7.51) were found, which were stronger when small studies randomizing <100 subjects per group were excluded.
  
  
  CONCLUSIONS
  Amiodarone has been demonstrated to be the most effective drug in maintaining sinus rhythm. Differences in outcomes between the anti-antiarrhythmic drugs were reported, with sotalol and possibly amiodarone increasing mortality and dronedarone possibly decreasing the incidence of serious adverse events and proarrhythmia.
authors.affiliation: School of Health and Population Sciences, 90 Vincent Drive, University of Birmingham Edgbaston, Birmingham B15 2SP, UK.
authors.forename: Nick
authors.initials: N
authors.lastname: Freemantle
authors.forename: Carmelo
authors.initials: C
authors.lastname: Lafuente-Lafuente
authors.forename: Stephen
authors.initials: S
authors.lastname: Mitchell
authors.forename: Laurent
authors.initials: L
authors.lastname: Eckert
authors.forename: Matthew
authors.initials: M
authors.lastname: Reynolds
mesh_terms: D000368:Aged; D000638:Amiodarone / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy*; D000077764:Dronedarone; D005260:Female; D005424:Flecainide / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D011405:Propafenone / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D013015:Sotalol / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000889:Anti-Arrhythmia Agents; D011405:Propafenone; D013015:Sotalol; D000077764:Dronedarone; D005424:Flecainide; D000638:Amiodarone