Increased Mortality Associated with Amiodarone Compared to Other Antiarrhythmic Drugs in New-Onset Atrial...

Background and Aims: Antiarrhythmic drugs (AADs) are the primary treatment for maintaining sinus rhythm in patients with atrial fibrillation (AF). While amiodarone is mainly used in patients with structural heart disease, its effects on all-cause mortality compared to other AADs remain unclear. Methods: This study utilized nationwide healthcare insurance data involving patients with new-onset AF from 2013 to 2019. We identified patients who were prescribed with AADs ≥ six months within the first year of diagnosis (medication possession ratio ≥ 0.5). All-cause mortality was assessed between amiodarone and other AAD users up to three years post-AAD-prescription. Results: Among 770,977 new-onset AF patients, 12,243 were amiodarone users and 33,036 were prescribed with other AADs. Significant differences in mean age and prevalence of medical conditions such as heart failure, myocardial infarction, chronic kidney disease, diabetes, and dyslipidemia were noted. After propensity score matching, 12,017 amiodarone users were compared to an equal number of other AAD users with similar baseline characteristics. Multivariate analysis indicated a 2.9-fold increase in all-cause mortality for amiodarone users (hazard ratio = 2.88; 95% confidence interval = 2.64-3.15; p < 0.001). This increased risk was more pronounced among women compared with men (hazard ratio = 3.38 vs. 2.56; p for interaction = 0.004). Amiodarone was associated with increased mortality in AF patients with heart failure and myocardial infarction. Conclusions: Amiodarone, compared with non-amiodarone AADs, was associated with increased risk of all-cause mortality in AAD-naive new-onset AF patients. Increased all-cause mortality associated with amiodarone was consistent throughout various subgroups. Significant interaction was observed with the sex category, with women being more vulnerable to amiodarone.