Combined Anticoagulant and antiplatelet therapy is associated with an improved outcome in hospitalized COVID-19 patients: a propensity matched cohort study
Authors: Matli Kamal , Chamoun Nibal , Fares Aya , Zibara Victor , Osta Soad Al , Nasrallah Rabih , Salameh Pascale , Mokhbat Jacques , Ghanem Georges 
Published: July 2021

Background

COVID-19 is a respiratory disease that results in a prothrombotic state manifesting as thrombotic, microthrombotic and thromboembolic events. As a result, several antithrombotic modalities have been implicated in the treatment of this disease. This study aimed to identify if therapeutic anticoagulation or concurrent use of antiplatelet and anticoagulants was associated with an improved outcome in this patient population.

Methods

A retrospective observational cohort study of adult patients admitted to a single university hospital for COVID-19 infection was performed. The primary outcome was a composite of in-hospital mortality, ICU admission, or the need for mechanical ventilation. The secondary outcomes were each of the components of the primary outcome, in-hospital mortality, ICU admission, or the need for mechanical ventilation.

Results

242 patients were included in the study and divided into 4 subgroups: therapeutic anticoagulation (TAC), prophylactic anticoagulation + antiplatelet (PACAP), therapeutic anticoagulation + antiplatelet (TACAP), and prophylactic anticoagulation (PAC) which was the reference for comparison. Multivariable cox regression analysis and propensity matching were done and showed when compared to PAC, TACAP and TAC were associated with less in-hospital all cause mortality with an adjusted hazard ratio (aHR) of 0.113 (95% confidence interval (CI) 0.028-0.449) and 0.126 (95% CI, 0.028-0.528) respectively. The number needed to treat (NNT) in both subgroups was 11. Furthermore, PACAP was associated with a reduced risk of invasive mechanical ventilation with an aHR of 0.07 (95% CI, 0.014-0.351). However, the was no statistically significant difference in the occurrence of major or minor bleeds, ICU admission, or the composite outcome of in-hospital mortality, ICU admission or the need for mechanical ventilation.

Conclusion

The use of combined anticoagulant and antiplatelet agents or therapeutic anticoagulation alone in hospitalized COVID-19 patients was associated with a better outcome in comparison to prophylactic anticoagulation alone without an increase in the risk of major and minor bleeds. Sufficiently powered randomized controlled trials are needed to further evaluate the safety and efficacy of combining antiplatelet and anticoagulants agents or using therapeutic anticoagulation in the management of patients with COVID-19 infection.

What is already known about this subject ?

Covid-19 infection is associated with several complex coagulation disorders resulting in thrombotic, microthrombotic and thromboembolic events. Currently, prophylactic dose anticoagulation is considered the standard of care antithrombotic regimen in hospitalized COVID-19 patients. However, high-quality data about the subject is unavailable.

What does this study add?

This is the first adequately sized study in the literature to dwell on the antithrombotic strategy consisting of combination anticoagulant and antiplatelet therapy in the treatment of COVID-19 induced hypercoagulable state. Furthermore, it also challenges the currently recommended prophylactic dosing of anticoagulation used in the treatment of those patients.

How might this impact on clinical practice?

Our data suggests for the first time that concurrent use of anticoagulant and antiplatelet therapy is associated with a superior clinical outcome as compared to prophylactic anticoagulation used alone. Furthermore, it solidifies the emerging evidence that therapeutic anticoagulation is linked to better clinical results than prophylactic anticoagulation.