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

Aims Mixed treatment comparisons (MTC) were performed to assess the relative efficacy and tolerability of the main antiarrhythmic 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.