Analysis of data on people with atrial fibrillation using anticoagulants and warfarin found them both to lower the risk of testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and severe disease.

COVID-19 disease may predispose some people to diseases related to blood clots because of disease severity or severe inflammatory response. Anticoagulants can help reduce the occurrence of such events in COVID-19 patients.

A few studies have reported that using anticoagulants like heparin can reduce the risk of blood clots in patients who have been hospitalized for COVID-19. Some studies have also looked at how oral coagulants can help, but these studies included people who likely had other comorbidities.

Vitamin K levels have also been reported to be decreased in COVID-19, and a correlation has been seen between vitamin K levels and COVID-19 severity. This then has implications for people who use warfarin, an anticoagulant that reduces the amount of vitamin K to make anticoagulant factors.

However, direct oral anticoagulants do not use vitamin K to prevent blood clots. They may be useful for treating coagulation-related disorders and a potentially lower risk for severe COVID-19.

In a new study, researchers investigated the association between the use of oral anticoagulants and warfarin in COVID-19 disease outcomes. They published their results in a paper on the medRxiv* preprint server.

Study: Association between oral anticoagulants and COVID-19 related outcomes: two cohort studies. Image Credit: NIAID

Testing the effect of anticoagulants

The researchers conducted two studies between March and September 2020. They used data sources that provided anonymized diagnoses, medication, and physiological parameters.

To compare the COVID-19 outcomes between oral anticoagulant users and non-users, the team included participants who suffered from atrial fibrillation and who used oral anticoagulants.

The team included about 52,000 oral anticoagulant users with a median age of 71 years and about 18,000 non-users with a median age of 69 years. They found a lower risk of testing positive for SARS-CoV-2 and COVID-19-related hospitalization and death in oral anticoagulant users compared to non-users.

To compare the COVID-19 outcomes between warfarin users and direct anticoagulant users, the researchers included participants with atrial fibrillation who used warfarin as the anticoagulant. This study included about 92,000 warfarin users with a median age of 79 years and about 280,000 users of direct anticoagulants with a median age of 78 years.

Statistical analysis indicated a lower risk of testing positive for SARS-CoV-2 and COVID-19-related hospitalization and death in warfarin users compared to direct anticoagulant users.

Thus, among people with atrial fibrillation, the analysis indicates a lower risk for testing positive for COVID-19 and death associated with it in people who take oral anticoagulants compared to people who did not take it. This lower risk was also seen in people who used warfarin.

Protective association between warfarin and COVID-19

There is some evidence that direct Xa inhibitors (anticoagulants) may hinder the entry of SARS-CoV-2 by preventing the splitting of the spike protein into the S1 and S2 subunits. Still, there is no clinical evidence of the protective effects of oral anticoagulants.

Another factor that may account for the lower risk is differences in behavior. The team compared the smoking status, alcohol use, and flu vaccinations. They found oral anticoagulant or warfarin users were less likely to be smokers, excessive alcohol drinkers, and more likely to have taken flu shots compared to non-users or direct oral anticoagulant users.

The authors found the protective association between warfarin use versus direct anticoagulant use in people with atrial fibrillation surprising. In particular, because warfarin has been associated with a possibly harmful effect and people who use warfarin generally have more comorbidities. The study helps provide evidence of the safety of using warfarin during the pandemic. Repeating these findings with more participants will probably help understand this effect better.

Although the results show an association between oral anticoagulant use and lesser risk of severe COVID-19, it is unknown if anticoagulants are a cause. The authors write, “if confirmed to be a causal effect, this could be of significant clinical importance, particularly as the older age and comorbidities in this group are independent risk factors of severe COVID-19 outcomes.”

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Lakshmi Supriya

Lakshmi Supriya got her BSc in Industrial Chemistry from IIT Kharagpur (India) and a Ph.D. in Polymer Science and Engineering from Virginia Tech (USA).