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

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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.

Original languageEnglish
Article number172
JournalJournal of Hematology and Oncology
Volume14
Issue number1
DOIs
Publication statusPublished - 19 Oct 2021
Externally publishedYes

Bibliographical note

Funding Information:
The OpenSAFELY data science platform is funded by the Wellcome Trust. OpenSAFELY work was jointly funded by UKRI, NIHR and Asthma UK-BLF [COV0076; MR/V015737/] and the Longitudinal Health and Wellbeing strand of the National Core Studies programme. TPP provided technical expertise and infrastructure within their data centre pro bono in the context of a national emergency. BG’s work on better use of data in healthcare more broadly is currently funded in part by: National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, NIHR Applied Research Collaboration Oxford and Thames Valley, the Mohn-Westlake Foundation, NHS England, and the Health Foundation; all DataLab staff are supported by BG’s grants on this work. LS reports grants from Wellcome, MRC, NIHR, UKRI, British Council, GSK, British Heart Foundation, and Diabetes UK outside this work. AYSW holds a fellowship from BHF. JPB is funded by a studentship from GSK. AS is employed by LSHTM on a fellowship sponsored by GSK. KB holds a Sir Henry Dale fellowship jointly funded by Wellcome and the Royal Society. HIM is funded by the NIHR Health Protection Research Unit in Immunisation, a partnership between Public Health England and LSHTM. RM holds a Sir Henry Wellcome fellowship. EW holds grants from MRC. RG holds grants from NIHR and MRC. ID holds grants from NIHR and GSK. HF holds a UKRI fellowship. The views expressed are those of the authors and not necessarily those of the NIHR, NHS England, Public Health England or the Department of Health and Social Care. This research was funded in part by Wellcome. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript (AAM) version arising from this submission. Funders had no role in the study design, collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

Funding Information:
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).

Publisher Copyright:
© 2021, The Author(s).

Keywords

  • COVID-19
  • Direct oral anticoagulants
  • Warfarin

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Oncology
  • Cancer Research

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