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. 2021 Oct 19;14(1):172.
doi: 10.1186/s13045-021-01185-0.

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

OpenSAFELY Collaborative; Angel Y S Wong  1 , Laurie A Tomlinson  2 , Jeremy P Brown  2 , William Elson  2 , Alex J Walker  3 , Anna Schultze  2 , Caroline E Morton  3 , David Evans  3 , Peter Inglesby  3 , Brian MacKenna  3 , Krishnan Bhaskaran  2 , Christopher T Rentsch  2 , Emma Powell  2 , Elizabeth Williamson  2 , Richard Croker  3 , Seb Bacon  3 , William Hulme  3 , Chris Bates  4 , Helen J Curtis  3 , Amir Mehrkar  3 , Jonathan Cockburn  4 , Helen I McDonald  2   5 , Rohini Mathur  2 , Kevin Wing  2 , Harriet Forbes  2 , Rosalind M Eggo  2 , Stephen J W Evans  2 , Liam Smeeth  2   5 , Ben Goldacre #  3 , Ian J Douglas #  2
Affiliations

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

OpenSAFELY Collaborative et al. J Hematol Oncol. .

Abstract

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.

Keywords: COVID-19; Direct oral anticoagulants; Warfarin.

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Conflict of interest statement

All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare the following: BG has received research funding from Health Data Research UK (HDRUK), the Laura and John Arnold Foundation, the Wellcome Trust, the NIHR Oxford Biomedical Research Centre, the NHS National Institute for Health Research School of Primary Care Research, the Mohn-Westlake Foundation, the Good Thinking Foundation, the Health Foundation, and the World Health Organisation; he also receives personal income from speaking and writing for lay audiences on the misuse of science. IJD has received unrestricted research grants and holds shares in GlaxoSmithKline (GSK).

Figures

Fig. 1
Fig. 1
Study diagram
Fig. 2
Fig. 2
Flow chart of inclusion of participants
Fig. 3
Fig. 3
Hazard ratios of the association between current use of warfarin and COVID-19-related outcomes and non-COVID-19 deaths, versus direct oral anticoagulants in people with non-valvular atrial fibrillation
See this image and copyright information in PMC

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