Association Between Digoxin Use and Adverse Outcomes Among Patients in the Chinese Atrial Fibrillation Registry

  • Ying Gao
  • Sanshuai Chang
  • Xin Du
  • Jianzeng Dong
  • Xiaoli Xu
  • Yingchun Zhou
  • Gregory Y. H. Lip
  • Changsheng MaEmail author
Original Research Article



Digoxin is widely used in patients with atrial fibrillation (AF), but its association with adverse outcomes remains controversial.


We aimed to assess the association between digoxin and adverse outcomes in Chinese patients with AF.


We used data from the Chinese Atrial Fibrillation Registry, a prospective, multicenter, hospital-based registry study involving 31 hospitals. In total, 10,472 eligible patients with AF, enrolled from August 2011 to December 2016, were included in this study. The association between digoxin use and all-cause mortality, cardiovascular death, and cardiovascular hospitalization were investigated using Cox proportional hazards models.


In total, 1152 (11%) patients were treated with digoxin at baseline. Patients receiving digoxin were older (mean age 69.7 vs. 66.5 years) and had a higher heart rate (92.4 vs. 79.7 beats/min). A higher proportion of patients receiving digoxin therapy had a history of heart failure (62.5 vs. 15.6%), diabetes mellitus (34.4 vs. 24.4%), and persistent AF (67.9 vs. 38.4%). Digoxin use was independently associated with increased all-cause mortality (adjusted hazard ratio (aHR) 1.21; 95% confidence interval (CI) 1.02–1.43; p = 0.031), cardiovascular death (aHR 1.25; 95% CI 1.01–1.55; p = 0.043), and cardiovascular hospitalization (aHR 1.21; 95% CI 1.05–1.39; p = 0.007). The associations were also homogeneous across various subgroups except in patients with and without renal dysfunction (p value for interaction = 0.029).


In this Chinese AF cohort, for patients who had not undergone ablation, digoxin use was associated with a significant increase in adverse outcomes. Although residual confounders may exist, and serum concentrations of digoxin were unavailable, digoxin should be used with caution in clinical practice, and its effects need to be critically evaluated in randomized trials.

Clinical trial registration

URL: Unique identifier: ChiCTR-OCH-13003729.


Compliance with Ethical Standards

Ethical standards

This study complied with standards required for observational study. Ethical approval was obtained from the Human Research Ethics Committees at Beijing Anzhen Hospital. Ethics review boards in each participating hospital approved their participation. Each patient provided informed consent for long-term follow-up.


This study was supported by a Grant (2013BAI09B02) from the Ministry of Science and Technology of the People’s Republic of China and Grants (ZYLX201302, D111100003011004, and D131100002313001) from the Beijing Municipal Commission of Science and Technology.

Conflict of interest

C.-S.M. has received honoraria from Bristol-Myers Squibb (BMS), Pfizer, Johnson & Johnson, Boehringer-Ingelheim (BI) and Bayer for giving lectures. J.-Z.D. has also received honoraria from Johnson & Johnson for giving lectures. G.Y.H.L. is or has been a consultant for Bayer/Janssen, BMS/Pfizer, Medtronic, BI, Novartis, Verseon, and Daiichi-Sankyo and a speaker for Bayer, BMS/Pfizer, Medtronic, BI, and Daiichi-Sankyo. YG, SC, XD, XX, and YZ have no conflicts of interest that are directly relevant to the content of this article.


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Ying Gao
    • 1
  • Sanshuai Chang
    • 1
  • Xin Du
    • 1
  • Jianzeng Dong
    • 1
  • Xiaoli Xu
    • 2
  • Yingchun Zhou
    • 2
  • Gregory Y. H. Lip
    • 3
    • 4
  • Changsheng Ma
    • 1
    Email author
  1. 1.Department of Cardiology, Beijing AnZhen Hospital, Capital Medical UniversityNational Clinical Research Centre for Cardiovascular DiseasesBeijingChina
  2. 2.Faculty of Economics and ManagementEast China Normal UniversityShanghaiChina
  3. 3.Institute of Cardiovascular SciencesUniversity of BirminghamBirminghamUK
  4. 4.Liverpool Centre for Cardiovascular ScienceLiverpoolUK

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