Journal Article

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

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

2021

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Administration, Oral / Adolescent / Adult / Aged / Aged, 80 and over / Anticoagulants / Anticoagulants - pharmacology / Anticoagulants - therapeutic use / Atrial fibrillation / Bias / Cancer Research / Cohort analysis / Cohort Studies / Comparative analysis / Coronaviruses / COVID-19 / COVID-19 - blood / COVID-19 - epidemiology / COVID-19 - virology / COVID-19 Drug Treatment / Direct oral anticoagulants / England - epidemiology / Fibrillation / Health aspects / Heart attacks / Hematology / Hospitals / Humans / Medicine / Medicine & Public Health / Middle Aged / Oncology / Population / Population studies / Population-based studies / Primary care / SARS-CoV-2 - isolation & purification / Severe acute respiratory syndrome coronavirus 2 / Software / Thromboembolism / Thromboembolism - blood / Thromboembolism - drug therapy / Thromboembolism - epidemiology / Thromboembolism - virology / Treatment Outcome / Vitamin K / Warfarin / Warfarin - therapeutic use / Young Adult