Antiarrhythmic therapy and risk of death in patients with atrial fibrillation: a nationwide study

Aims To examine the risk of death associated with antiarrhythmic drug (AAD) therapy in a nationwide unselected cohort of patients with atrial fibrillation (AF). Methods and results All patients admitted with AF in Denmark from 1995 to 2004 and their subsequent use of AADs were identified by individual-level linkage of nationwide registries. Multivariable Cox proportional-hazard models with time-dependent covariates were used to analyse the risk of death associated with AAD therapy. A total of 141 500 patients were included in the study; of these 3356 (2.4%) patients received treatment with flecainide, 3745 (2.6%) propafenone, 23 346 (16.5%) sotalol, and 10 376 (7.3%) amiodarone. Annualized mortality rates were 2.54, 4.25, 5.29, and 7.42 per year per 100 person years for flecainide, propafenone, sotalol, and amiodarone, respectively. Multivariable Cox proportional-hazard models did not show increased risk of death associated with any of the AADs. Hazard ratio (95% confidence interval) for flecainide 0.38 (0.32-0.44), propafenone 0.65 (0.58-0.71), sotalol 0.65 (0.63-0.67), and amiodarone 0.94 (0.89-1.00). Conclusion In an unselected cohort of patients with AF, antiarrhythmic treatment with flecainide, propafenone, sotalol, or amiodarone was not associated with increased risk of death. From a safety perspective, this indicates appropriate selection of patients for AAD therapy.