title: Amiodarone use is associated with increased risk of stroke in patients with nonvalvular atrial fibrillation: a nationwide population-based cohort study.
abstract: Atrial fibrillation (AF), the most common sustained arrhythmia requiring treatment worldwide, is one of the major causes of ischemic stroke. Although amiodarone is commonly used for rhythm control in AF, its relationship with stroke has rarely been addressed.We evaluated 16,091 patients who were diagnosed with AF (Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] 427.31 and 427.32) between 1998 and 2011; the date of AF diagnosis was set as the index date. Patients with a history of stroke (ICD-9-CM 430-438) who received amiodarone before the index date or during the following 30 days, or who experienced stroke within 30 days of receiving amiodarone were excluded. Finally, 7548 patients with AF were included in this study and divided into 2 groups according to whether they received amiodarone (Anatomical Therapeutic Chemical code C01BD01) during the study period.The risk of ischemic stroke in AF patients receiving amiodarone was 1.81-fold (95% confidence interval [CI] 1.52-2.16), 1.79-fold (95% CI 1.50-2.14), and 1.78-fold (95% CI 1.49-2.13) higher than in those who did not receive amiodarone, according to crude, Model 1, and Model 2 Cox proportional hazard regression models, respectively. In a demographically stratified analysis, the risk of ischemic stroke was significantly higher in patients aged <65 years, with no comorbidities, who were also taking digoxin or had a low CHA2DS2VASc score.Amiodarone treatment is associated with an increased risk of stroke in patients with AF, especially in those who have an initial low risk of stroke. Antiplatelet drugs and warfarin could reduce the stroke risk in AF patients receiving amiodarone. However, as the combination of digoxin and amiodarone increases the risk of stroke in these patients, the combination of these 2 drugs should be avoided.
authors.affiliation: From the Hyperbaric Oxygen Therapy Center (W-Chun Chen, W-Cheng Chen, T-CH, W-CL, C-HL), China Medical University Hospital; Division of Cardiology (K-HL), Department of Internal Medicine, China Medical University Hospital; Department of Life Science (K-HL), National Chung Hsing University, Taiwan; Division of Pulmonary and Critical Care Medicine (WC), Chia-Yi Christian Hospital, Taiwan; Management Office for Health Data (C-HM), China Medical University Hospital, China Medical University, Taichung, Taiwan.
authors.forename: Wei-Chun
authors.initials: WC
authors.lastname: Chen
authors.forename: Wei-Cheng
authors.initials: WC
authors.lastname: Chen
authors.forename: Chih-Yu
authors.initials: CY
authors.lastname: Chen
authors.forename: Biing-Ru
authors.initials: BR
authors.lastname: Wu
authors.forename: Wen-Chien
authors.initials: WC
authors.lastname: Cheng
authors.forename: Kuo-Hung
authors.initials: KH
authors.lastname: Lin
authors.forename: Te-Chun
authors.initials: TC
authors.lastname: Hsia
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Chen
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Muo
authors.forename: Wei-Chih
authors.initials: WC
authors.lastname: Liao
authors.forename: Chia-Hsiang
authors.initials: CH
authors.lastname: Li
mesh_terms: D000367:Age Factors; D000368:Aged; D000638:Amiodarone / Q000009:adverse effects* / Q000627:therapeutic use; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000925:Anticoagulants / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000188:drug therapy*; D015897:Comorbidity; D004077:Digoxin / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012307:Risk Factors; D020521:Stroke / Q000139:chemically induced*; D013624:Taiwan / Q000453:epidemiology; D014859:Warfarin / Q000627:therapeutic use
chemical_list: D000889:Anti-Arrhythmia Agents; D000925:Anticoagulants; D014859:Warfarin; D004077:Digoxin; D000638:Amiodarone