Amiodarone is associated with increased mortality compared with other antiarrhythmic drugs in female patients with atrial fibrillation

Abstract

Abstract Objective Antiarrhythmic drug (AAD) is the first-line therapy in patients with atrial fibrillation (AF) to maintain sinus rhythm. Amiodarone is one of the commonly used AAD that is known to lead to cardiac and extra-cardiac toxicities including pulmonary fibrosis and thyroid function abnormalities. However, the effect of amiodarone as compared with other-AADs (mainly Ic sodium channel blockers) on all-cause mortality is not fully evaluated. Methods This study used nationwide healthcare insurance system data. Patients with new-onset AF between 2013 and 2019 were enrolled. Use of AADs were confirmed if the patient were prescribed with AAD for more than six months during first year of AF diagnosis (medication possession ratio > 0.5). Clinical follow-up duration was three years from the moment AAD prescription after AF diagnosis. All-cause mortality was compared between amiodarone vs. other-AAD users. Results A total of 770,977 new-onset AF cases were detected. Among these people, 15,142 and 38,707 were identified as amiodarone and other-AAD users, respectively. Significant differences were observed in mean age and prevalence of heart failure, myocardial infarction, chronic kidney disease, diabetes mellitus, and dyslipidemia. After propensity score matching, 9,672 amiodarone users were compared with other-AAD users with same sample size and baseline characteristics were well matched. In multivariate adjusted analysis, amiodarone was associated with 2.5-fold increase in all-cause mortality (hazard ratio=2.520; 95% confidence interval=2.202 – 2.883; p< 0.001). Amiodarone did not show any significant interactions with age, thyroid disease, chronic kidney disease, heart failure, myocardial infarction, diabetes mellitus, dyslipidemia, and hypertension. However, the association between amiodarone and increased mortality was more pronounced in women compared with men (HR=3.124 vs. 2.231; p for interaction=0.022). Conclusion This study showed that all-cause mortality was significantly higher in amiodarone users than other-AAD users due to the toxicities, not by underlying diseases, which was more profound in female. This findings suggests that avoiding amiodarone as a first-line therapy should be considered in AF patients who have no compelling indications such as significant coronary artery disease or heart failure.All-cause mortality