No benefit of low dose apixaban following acute COVID-19

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The long-term adverse effects of infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic, are well documented. The manifestation of these symptoms, which is often referred to as ‘long-COVID,’ in severely infected COVID-19 patients has similarly been reported in many studies.

Study: Apixaban following discharge in hospitalised adults with COVID-19: Preliminary results from a multicentre, open-label, randomised controlled platform clinical trial. Image Credit: WHYFRAME /

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.


Individuals severely infected with SARS-CoV-2 are at a higher risk of developing pulmonary and cardiovascular complications, with potentially long-lasting consequences, such as persistent inflammation, venous thromboembolism, and pulmonary fibrosis. Several therapeutic approaches have been identified to treat the acute stage of COVID-19; however, there remains a lack of specific therapies capable of effectively treating long COVID.

A recent retrospective cohort study that included about 48,000 individuals with acute SARS-CoV-2 infection who were admitted to National Health Service (NHS) hospitals in England revealed that about 29% of these patients had been readmitted, while 12% had died following discharge. A similar pattern was also observed in another study based in the United States.

In the case of severe SARS-CoV-2 infection, coagulation abnormalities were observed, associated with platelet activation and clotting factors. In addition, a high incidence of thromboembolic events was reported during the post-acute phase of COVID-19.

Due to inconsistencies in the risk estimation of anticoagulant treatment, an effective therapeutic decision regarding the use of anticoagulant drugs could not be made. Therefore, itentifying effective pharmacological prophylactic agents capable of reducing the risk of venous thromboembolism in COVID-19 convalescent adults is imperative.

The National Institute for Health and Care Excellence (NICE) failed to identify research that determined the effectiveness and safety of pharmacological prophylaxis to reduce the risk of venous thromboembolism in adults who have received care for COVID-19. However, NICE has published some relevant guidelines for the clinical management of COVID-19.

About the study

HEAL-COVID is a recent adaptive, randomized, open-label, multicenter, multi-arm, and multi-stage platform trial that addresses this gap in research. This trial compared the post-hospital treatments to standard care among adults who required hospitalization after contracting severe SARS-CoV-2 infection.

Apixaban, an oral direct-acting anticoagulant, was selected as an arm for the trial. Apixaban was chosen due to its oral route of administration, promising safety profiles, and widespread availability. The findings of this study have been recently published on the medRxiv* preprint server.

In this study, follow-up data were obtained through data linkage to routine clinical data sources. Additionally, self-reported data of the patients were collected through an app/web-based system (ATOM5) or telephone calls conducted by the research team.

A total of 1,194 participants were selected from NHS hospitals in England, Wales, Northern Ireland, and Scotland between May 19, 2021, and November 21, 2022.

All participants were randomly assigned to two groups. One group received 2.5 mg of Apixaban twice daily for 14 days, while the other group received standard care, which did not involve post-hospital anticoagulants. The patients in both groups were monitored for 12 months.

Study findings

Fourteen days of Apixaban treatment did not reduce subsequent hospital readmission or death rates. Furthermore, the hospital admission rate remained similar to that recorded before the commencement of the COVID-19 vaccination program and the application of various therapeutics, such as Tocilizumab, Dexamethasone, and antivirals.

An increased risk of thromboembolism in the first four weeks after SARS-CoV-2 infection has been reported. This observation is consistent with the HEAL-COVID analytical data, which revealed that most venous thromboembolic events occurred within the first thirty days of the trial.

In the standard care group, four pulmonary embolism cases occurred within the first 30 days; however, this event was not reported in the Apixaban group. Nevertheless, two participants from the Apixaban group required hospital readmission due to bleeding within the same period.

These findings indicated that standard and anticoagulant treatment's risk-benefit ratio is finely balanced. Thus, the HEAL-COVID trial failed to demonstrate the overall benefits of Apixaban treatment in terms of mortality and hospital readmission, even after one year. 

In-hospital anticoagulation treatment, along with Rivaroxaban for up to 30 days, did not improve death rates, duration of hospitalization, or oxygen requirements. Notably, in multiple patient cohorts, Rivaroxaban caused a higher rate of bleeding than Apixaban.


Fourteen days of post-hospital Apixaban treatment failed to reduce death rates or rehospitalization in adults who have recently recovered from severe SARS-CoV-2 infection. Thus, the current study does not recommend post-hospital anticoagulation treatment. Notably, the authors hypothesized that longer treatment would not provide any additional benefits and would increase the risk of bleeding in these patients.

*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.

Journal reference:
Dr. Priyom Bose

Written by

Dr. Priyom Bose

Priyom holds a Ph.D. in Plant Biology and Biotechnology from the University of Madras, India. She is an active researcher and an experienced science writer. Priyom has also co-authored several original research articles that have been published in reputed peer-reviewed journals. She is also an avid reader and an amateur photographer.


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