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Published in: Journal of Hematology & Oncology 1/2021

Open Access 01-12-2021 | Direct Oral Anticoagulant | Research

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

Authors: 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. Curtis, Amir 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, The OpenSAFELY Collaborative

Published in: Journal of Hematology & Oncology | Issue 1/2021

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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.
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Literature
1.
go back to reference Malas MB, Naazie IN, Elsayed N, Mathlouthi A, Marmor R, Clary B. Thromboembolism risk of COVID-19 is high and associated with a higher risk of mortality: a systematic review and meta-analysis. EClinicalMedicine. 2020;29:100639.CrossRef Malas MB, Naazie IN, Elsayed N, Mathlouthi A, Marmor R, Clary B. Thromboembolism risk of COVID-19 is high and associated with a higher risk of mortality: a systematic review and meta-analysis. EClinicalMedicine. 2020;29:100639.CrossRef
4.
go back to reference Harrison RF, Forte K, Buscher MG Jr, et al. The Association of preinfection daily oral anticoagulation use and all-cause in hospital mortality from novel coronavirus 2019 at 21 days: a retrospective cohort study. Crit Care Explor. 2021;3(1):e0324.CrossRef Harrison RF, Forte K, Buscher MG Jr, et al. The Association of preinfection daily oral anticoagulation use and all-cause in hospital mortality from novel coronavirus 2019 at 21 days: a retrospective cohort study. Crit Care Explor. 2021;3(1):e0324.CrossRef
5.
go back to reference Flam B, Wintzell V, Ludvigsson JF, Mårtensson J, Pasternak B. Direct oral anticoagulant use and risk of severe COVID-19. J Intern Med. 2021;289(3):411–9.CrossRef Flam B, Wintzell V, Ludvigsson JF, Mårtensson J, Pasternak B. Direct oral anticoagulant use and risk of severe COVID-19. J Intern Med. 2021;289(3):411–9.CrossRef
7.
go back to reference Rossi R, Coppi F, Talarico M, Boriani G. Protective role of chronic treatment with direct oral anticoagulants in elderly patients affected by interstitial pneumonia in COVID-19 era. Eur J Intern Med. 2020;77:158–60.CrossRef Rossi R, Coppi F, Talarico M, Boriani G. Protective role of chronic treatment with direct oral anticoagulants in elderly patients affected by interstitial pneumonia in COVID-19 era. Eur J Intern Med. 2020;77:158–60.CrossRef
10.
go back to reference Vinogradova Y, Coupland C, Hippisley-Cox J. Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ. 2019;364:k4810.CrossRef Vinogradova Y, Coupland C, Hippisley-Cox J. Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ. 2019;364:k4810.CrossRef
11.
go back to reference Steinhubl SR, Eikelboom JW, Hylek EM, Dauerman HL, Smyth SS, Becker RC. Antiplatelet therapy in prevention of cardio- and venous thromboembolic events. J Thromb Thrombolysis. 2014;37(3):362–71.CrossRef Steinhubl SR, Eikelboom JW, Hylek EM, Dauerman HL, Smyth SS, Becker RC. Antiplatelet therapy in prevention of cardio- and venous thromboembolic events. J Thromb Thrombolysis. 2014;37(3):362–71.CrossRef
12.
go back to reference Ding P, Vander Weele TJ. Sensitivity analysis without assumptions. Epidemiology. 2016;27(3):368–77.CrossRef Ding P, Vander Weele TJ. Sensitivity analysis without assumptions. Epidemiology. 2016;27(3):368–77.CrossRef
13.
go back to reference Vinogradova Y, Coupland C, Hill T, Hippisley-Cox J. Risks and benefits of direct oral anticoagulants versus warfarin in a real world setting: cohort study in primary care. BMJ. 2018;362:k2505.CrossRef Vinogradova Y, Coupland C, Hill T, Hippisley-Cox J. Risks and benefits of direct oral anticoagulants versus warfarin in a real world setting: cohort study in primary care. BMJ. 2018;362:k2505.CrossRef
14.
go back to reference Guan W-J, Ni Z-Y, Hu Y, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020;382(18):1708–20.CrossRef Guan W-J, Ni Z-Y, Hu Y, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020;382(18):1708–20.CrossRef
15.
go back to reference Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054–62.CrossRef Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054–62.CrossRef
16.
go back to reference Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18(4):844–7.CrossRef Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18(4):844–7.CrossRef
17.
go back to reference Rico-Mesa JS, Rosas D, Ahmadian-Tehrani A, White A, Anderson AS, Chilton R. The role of anticoagulation in COVID-19-induced hypercoagulability. Curr Cardiol Rep. 2020;22(7):53.CrossRef Rico-Mesa JS, Rosas D, Ahmadian-Tehrani A, White A, Anderson AS, Chilton R. The role of anticoagulation in COVID-19-induced hypercoagulability. Curr Cardiol Rep. 2020;22(7):53.CrossRef
18.
go back to reference Bikdeli B, Madhavan MV, Jimenez D, et al. COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up: JACC state-of-the-art review. J Am Coll Cardiol. 2020;75(23):2950–73.CrossRef Bikdeli B, Madhavan MV, Jimenez D, et al. COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up: JACC state-of-the-art review. J Am Coll Cardiol. 2020;75(23):2950–73.CrossRef
19.
go back to reference Cranenburg ECM, Schurgers LJ, Uiterwijk HH, et al. Vitamin K intake and status are low in hemodialysis patients. Kidney Int. 2012;82(5):605–10.CrossRef Cranenburg ECM, Schurgers LJ, Uiterwijk HH, et al. Vitamin K intake and status are low in hemodialysis patients. Kidney Int. 2012;82(5):605–10.CrossRef
Metadata
Title
Association between warfarin and COVID-19-related outcomes compared with direct oral anticoagulants: population-based cohort study
Authors
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. Curtis
Amir 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
The OpenSAFELY Collaborative
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2021
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-021-01185-0

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