Association between oral anticoagulants and COVID-19 related outcomes: two cohort studies
Authors:   The OpenSAFELY Collaborative, Wong Angel YS , Tomlinson Laurie , 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 JW , Smeeth Liam , Goldacre Ben , Douglas Ian J 
Published: April 2021

Objectives

We investigated the role of routinely prescribed oral anticoagulants (OACs) in COVID-19 outcomes, comparing current OAC use versus non-use in Study 1; and warfarin versus direct oral anticoagulants (DOACs) in Study 2.

Design

Two cohort studies, on behalf of NHS England.

Setting

Primary care data and pseudonymously-linked SARS-CoV-2 antigen testing data, hospital admissions, and death records from England.

Participants

Study 1: 70,464 people with atrial fibrillation (AF) and CHA□DS□-VASc score of 2. Study 2: 372,746 people with non-valvular AF.

Main outcome measures

Time to test for SARS-CoV-2, testing positive for SARS-CoV-2, COVID-19 related hospital admission, COVID-19 deaths or non-COVID-19 deaths in Cox regression.

Results

In Study 1, we included 52,416 current OAC users and 18,048 non-users. We observed no difference in risk of being tested for SARS-CoV-2 associated with current use (adjusted HR, 1.01, 95%CI, 0.96 to 1.05) versus non-use. We observed a lower risk of testing positive for SARS-CoV-2 (adjusted HR, 0.73, 95%CI, 0.60 to 0.90), and COVID-19 deaths (adjusted HR, 0.69, 95%CI, 0.49 to 0.97) associated with current use versus non-use. In Study 2, we included 92,339 warfarin users and 280,407 DOAC users. We observed a lower risk of COVID-19 deaths (adjusted HR, 0.79, 95%CI, 0.76 to 0.83) associated with warfarin versus DOACs. Similar associations were found for all other outcomes.

Conclusions

Among people with AF and a CHA□DS□-VASc score of 2, those receiving OACs had a lower risk of receiving a positive COVID-19 test and severe COVID-19 outcomes than non-users; this might be explained by a causal effect of OACs in preventing severe COVID-19 outcomes or more cautious behaviours leading to reduced infection risk. There was no evidence of a higher risk of severe COVID-19 outcomes associated with warfarin versus DOACs in people with non-valvular AF regardless of CHA□DS□-VASc score.

Key points

What is already known on this topic

Current studies suggest that prophylactic or therapeutic anticoagulant use, particularly low molecular weight heparin, lower the risk of pulmonary embolism and mortality during hospitalisation among patients with COVID-19.

Reduced vitamin K status has been reported to be correlated with severity of COVID-19. This could mean that warfarin, as a vitamin K antagonist, is associated with more severe COVID-19 disease than non-vitamin K anticoagulants.

What this study adds

In 70,464 people with atrial fibrillation, at the threshold of being treated with an OAC based on risk of stroke, we observed a lower risk of testing positive for SARS-CoV-2 and COVID-19 related deaths associated with routinely prescribed OACs, relative to non-use.

This might be explained by OACs preventing severe COVID-19 outcomes, or more cautious behaviours and environmental factors reducing the risk of SARS-CoV-2 infection in those taking OACs.

In 372,746 people with non-valvular atrial fibrillation, there was no evidence of a higher risk of severe COVID-19 outcomes associated with warfarin compared with DOACs.