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

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

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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13045-021-01185-0.