Article Text

Original research
Discontinuation of oral anticoagulation in atrial fibrillation and risk of ischaemic stroke
  1. Luis Alberto García Rodríguez1,
  2. Lucía Cea Soriano2,
  3. Stine Munk Hald3,
  4. Jesper Hallas3,
  5. Yanina Balabanova4,
  6. Gunnar Brobert5,
  7. Pareen Vora4,
  8. Mike Sharma6,
  9. David Gaist3
  1. 1Spanish Centre for Pharmacoepidemiologic Research (CEIFE), Madrid, Spain
  2. 2Complutense University of Madrid, Madrid, Spain
  3. 3University of Southern Denmark, Odense, Denmark
  4. 4Bayer AG, Berlin, Germany
  5. 5Bayer AB, Stockholm, Sweden
  6. 6McMaster University, Hamilton, Ontario, Canada
  1. Correspondence to Dr Luis Alberto García Rodríguez, Spanish Centre for Pharmacoepidemiologic Research (CEIFE), Madrid, Spain; lagarcia{at}


Objective To evaluate associations between oral anticoagulant (OAC) discontinuation and risk of ischaemic stroke (IS) among patients with atrial fibrillation (AF).

Methods We undertook a population-based cohort study with nested case–control analysis using UK primary care electronic health records (IQVIA Medical Research Data-UK) and linked registries from the Region of Southern Denmark (RSD). Patients with AF (76 882 UK, 41 526 RSD) were followed to identify incident IS cases during 2016–2018. Incident IS cases were matched by age and sex to controls. Adjusted ORs for OAC discontinuation (vs current OAC use) were calculated using logistic regression.

Results We identified 616 incident IS cases in the UK and 643 in the RSD. ORs for IS with any OAC discontinuation were 2.99 (95% CI 2.31 to 3.86, UK) and 2.30 (95% CI 1.79 to 2.95, RSD), for vitamin K antagonist discontinuation they were 2.38 (95% CI 1.72 to 3.30, UK) and 1.83 (95% CI 1.34 to 2.49, RSD), and for non-vitamin K antagonist oral anticoagulant discontinuation they were 4.59 (95% CI 2.97 to 7.08, UK) and 3.37 (95% CI 2.35 to 4.85, RSD). ORs were unaffected by time since discontinuation and duration of use. Annually, up to 987 IS cases in the UK and 132 in Denmark could be preventable if OAC therapy is not discontinued.

Conclusions Our results suggest that patients with AF who discontinue OAC therapy have a significant twofold to threefold higher risk of IS compared with those who continue therapy. Addressing OAC discontinuation could potentially result in a significant reduction in AF-attributed IS.

  • atrial fibrillation
  • stroke
  • epidemiology
  • electronic medical records

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  • Presented at Two abstracts containing data from this study have been accepted for presentation at the European Stroke Organisation Conference to be held in November 2020.

  • Contributors LAGR, DG, YB, GB and PV contributed to the design of the study. LCS, LAGR and DG extracted the data and performed the statistical analysis. All authors contributed to the interpretation of the data and the review of manuscript drafts, and all approved the final manuscript. LAGR is the guarantor. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

  • Funding The UK part of this study was funded by Bayer AG. The Danish part of this study did not receive funding; the activities of David Gaist are supported by a grant from Odense University Hospital. Bayer had no role in the study apart from salaries paid to YB, GB and PV whose contributions to the study are mentioned above. All authors had full access to all of the data (including statistical reports and tables) in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis is also required.

  • Competing interests LAGR works for CEIFE, which has received other research funding from Bayer AG. LAGR has also received honoraria for serving on advisory boards for Bayer AG. DG has received honoraria from AstraZeneca (Sweden) for participation as a co-investigator on a research project outside the submitted work, and receiving speaker honorarium from Bristol-Myers Squibb outside the submitted work. YB and PV are employees of Bayer AG. GB is an employee of Bayer AB. MS has served on the steering committees and led sub-studies from trials sponsored by Bayer and has served as a consultant and received speaker’s honoraria from Bayer. MS has also served as a consultant to Portola, Bristol Myers Squibb and Janssen. LCS, SMH and JH report no potential conflicts of interest.

  • Patient consent for publication Not required.

  • Ethics approval The UK and Denmark studies were approved by the Independent Scientific Research Committee for IMRD-UK (reference no. 19THIN057) and the Danish Data Protection Agency, respectively. Data collection for IMRD-UK was approved by the South East Multicentre Research Ethics Committee in 2003 and individual studies using IMRD-UK data do not require separate ethical approval if only anonymised data are used. Danish law does not require approval from an ethics board or informed consent for register studies.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available from the corresponding author upon reasonable request.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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