Abstract 2752: Morbidity and Mortality Associated With Anti-Arrhythmic Drugs in Atrial Fibrillation: A Systematic Review and Mixed Treatment Meta-Analysis

Abstract

Objective: Mixed treatment comparison (MTC) is increasingly used to estimate the treatment effects when directly randomised comparisons are not available. MTCs make the best use of the available data, particularly to support decision analytic models. We performed a MTC to compare the risk of morbidity and mortality associated with the novel AAD dronedarone, amiodarone, sotalol, flecainide and propafenone.

Methods: Randomised controlled trials (RCTs), in patients with AF were systematically reviewed. Analyses were conducted on an intention-to-treat basis, using MTC models in order to combine direct and indirect comparisons in a single analysis.

Results: Dronedarone vs. Placebo (odds ratio (OR) 0.85; 95% CI 0.67 to 1.09) was associated with a significantly lower risk of death than amiodarone Vs placebo (OR 2.73; 95% CI 1.00 to 7.41), (Dronedarone Vs Amiodarone P = .03) and significantly less than sotalol Vs placebo (OR 4.32; 95% CI 1.59 to11.70), (Dronedarone Vs Sotalol P = .009). Sparse data on the effects of flecainide and propafenone prevented estimation for those comparisons. For CV morbidity, there was only sufficient data for stroke and no data were available for flecainide and propafenone. Dronedarone vs placebo achieved a statistically significant reduction in stroke (OR 0.69; 95% CI 0.57 to 0.84), while neither amiodarone Vs placebo (OR 0.89; 95% CI 0.48 to 1.65) nor sotalol Vs placebo (OR 0.80; 95% CI 0.39 to 1.63) achieved significant results. Dronedarone Vs placebo (OR 0.98; 95% CI 0.74 to 1.30) had the lowest rate of serious adverse events compared to amiodarone Vs placebo (OR 1.82; 95% CI 0.73 to 4.57), sotalol Vs placebo (OR 1.32; 95% CI 0.75 to 2.32) flecainide Vs placebo (OR 2.82; 95% CI 0.40 to 19.96) and propafenone Vs placebo (OR 3.08; 95% CI 0.73 to 13.04), however these comparisons were not statistically significant.

Conclusion: Dronedarone has been evaluated in RCTs Vs placebo and amiodarone. The MTC, which combines direct and indirect (via placebo) treatment effects, found that dronedarone is associated with a significant reduction in mortality compared to amiodarone and sotalol. Dronedarone achieved a significant reduction in the rate of stroke compared to placebo, and may be associated with less serious adverse events than other AADs.