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.