Association between warfarin and COVID-19-related outcomes compared with direct oral anticoagulants: population-based cohort study

The OpenSAFELY Collaborative, Angel Y.S. Wong*, Laurie A. Tomlinson, Jeremy P. Brown, William Elson, Alex J. Walker, Anna Schultze, Caroline E. Morton, David Evans, Peter Inglesby, Brian MacKenna, Krishnan Bhaskaran, Christopher T. Rentsch, Emma Powell, Elizabeth Williamson, Richard Croker, Seb Bacon, William Hulme, Chris Bates, Helen J. CurtisAmir Mehrkar, Jonathan Cockburn, Helen I. McDonald, Rohini Mathur, Kevin Wing, Harriet Forbes, Rosalind M. Eggo, Stephen J.W. Evans, Liam Smeeth, Ben Goldacre, Ian J. Douglas

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background: Thromboembolism has been reported as a consequence of severe COVID-19. Although warfarin is a commonly used anticoagulant, it acts by antagonising vitamin K, which is low in patients with severe COVID-19. To date, the clinical evidence on the impact of regular use of warfarin on COVID-19-related thromboembolism is lacking. Methods: On behalf of NHS England, we conducted a population-based cohort study investigating the association between warfarin and COVID-19 outcomes compared with direct oral anticoagulants (DOACs). We used the OpenSAFELY platform to analyse primary care data and pseudonymously linked SARS-CoV-2 antigen testing data, hospital admissions and death records from England. We used Cox regression to estimate hazard ratios (HRs) for COVID-19-related outcomes comparing warfarin with DOACs in people with non-valvular atrial fibrillation. We also conducted negative control outcome analyses (being tested for SARS-CoV-2 and non-COVID-19 death) to assess the potential impact of confounding. Results: A total of 92,339 warfarin users and 280,407 DOAC users were included. We observed a lower risk of all outcomes associated with warfarin versus DOACs [testing positive for SARS-CoV-2, HR 0.73 (95% CI 0.68–0.79); COVID-19-related hospital admission, HR 0.75 (95% CI 0.68–0.83); COVID-19-related deaths, HR 0.74 (95% CI 0.66–0.83)]. A lower risk of negative control outcomes associated with warfarin versus DOACs was also observed [being tested for SARS-CoV-2, HR 0.80 (95% CI 0.79–0.81); non-COVID-19 deaths, HR 0.79 (95% CI 0.76–0.83)]. Conclusions: Overall, this study shows no evidence of harmful effects of warfarin on severe COVID-19 disease.

Original languageEnglish
Article number172
JournalJournal of Hematology and Oncology
Issue number1
Early online date19 Oct 2021
Publication statusPublished - 1 Dec 2021


  • COVID-19
  • Direct oral anticoagulants
  • Warfarin


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