title: Does digoxin increase the risk of ischemic stroke and mortality in atrial fibrillation? A nationwide population-based cohort study.
abstract: BACKGROUND
  Digoxin and related cardiac glycosides have been used for almost 100 years in atrial fibrillation (AF). However, 2 recent analyses of the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) trial showed inconsistent results regarding the risk of mortality associated with digoxin use. The goal of the present study was to investigate the relationship between digoxin and the risk of ischemic stroke and mortality in Asians.
  
  
  METHODS
  This study used the National Health Insurance Research Database (NHIRD) in Taiwan. A total of 4781 patients with AF who did not receive any antithrombotic therapy were selected as the study population. Among the study population, 829 participants (17.3%) received the digoxin treatment. The risk of ischemic stroke and mortality in patients who received digoxin and those who did not was compared.
  
  
  RESULTS
  The use of digoxin was associated with an increased risk of clinical events, with an adjusted hazard ratio of 1.41 (95% confidence interval [CI], 1.17-1.70) for ischemic stroke and 1.21 (95% CI, 1.01-1.44) for all-cause mortality. In the subgroup analysis based on coexistence with heart failure or not, digoxin was a risk factor for adverse events in patients without heart failure but not in those with heart failure (interaction P < 0.001 for either end point). Among patients with AF without heart failure, the use of β-blockers was associated with better survival, with an adjusted hazard ratio of 0.48 (95% CI, 0.34-0.68).
  
  
  CONCLUSIONS
  Digoxin should be avoided for patients with AF without heart failure because it was associated with an increased risk of clinical events. β-Blockers may be a better choice for controlling ventricular rate in these patients.
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine and Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Tze-Fan
authors.initials: TF
authors.lastname: Chao
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Public Health and School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Internal Medicine, National Yang-Ming University Hospital, I-Lan, Taiwan.
authors.forename: Chia-Jen
authors.initials: CJ
authors.lastname: Liu
authors.affiliation: Institute of Public Health and School of Medicine, National Yang-Ming University, Taipei, Taiwan; Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital Su-Ao and Yuanshan Branch, I-Lan, Taiwan.
authors.forename: Su-Jung
authors.initials: SJ
authors.lastname: Chen
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine and Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Kang-Ling
authors.initials: KL
authors.lastname: Wang
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine and Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yenn-Jiang
authors.initials: YJ
authors.lastname: Lin
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine and Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Shih-Lin
authors.initials: SL
authors.lastname: Chang
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine and Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Li-Wei
authors.initials: LW
authors.lastname: Lo
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine and Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Hu
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine and Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Ta-Chuan
authors.initials: TC
authors.lastname: Tuan
authors.affiliation: Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Tzeng-Ji
authors.initials: TJ
authors.lastname: Chen
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine and Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan; General Clinical Research Center, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan. Electronic address: cechiang@vghtpe.gov.tw.
authors.forename: Chern-En
authors.initials: CE
authors.lastname: Chiang
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine and Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan. Electronic address: epsachen@ms41.hinet.net.
authors.forename: Shih-Ann
authors.initials: SA
authors.lastname: Chen
mesh_terms: D000889:Anti-Arrhythmia Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000150:complications* / Q000188:drug therapy / Q000401:mortality*; D002545:Brain Ischemia / Q000453:epidemiology*; D015331:Cohort Studies; D004077:Digoxin / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology*
chemical_list: D000889:Anti-Arrhythmia Agents; D004077:Digoxin