Mixed treatment comparison of dronedarone, amiodarone, sotalol, flecainide, and propafenone, for the management of atrial fibrillation

Europace. 2011 Mar;13(3):329-45. doi: 10.1093/europace/euq450. Epub 2011 Jan 11.


Aims: 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.

Methods and 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.

Publication types

  • Comparative Study
  • Meta-Analysis

MeSH terms

  • Aged
  • Amiodarone / adverse effects
  • Amiodarone / analogs & derivatives
  • Amiodarone / therapeutic use
  • Anti-Arrhythmia Agents / adverse effects*
  • Anti-Arrhythmia Agents / therapeutic use*
  • Atrial Fibrillation / drug therapy*
  • Dronedarone
  • Female
  • Flecainide / adverse effects
  • Flecainide / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Propafenone / adverse effects
  • Propafenone / therapeutic use
  • Randomized Controlled Trials as Topic
  • Sotalol / adverse effects
  • Sotalol / therapeutic use
  • Treatment Outcome


  • Anti-Arrhythmia Agents
  • Propafenone
  • Sotalol
  • Dronedarone
  • Flecainide
  • Amiodarone