Combined anticoagulant and antiplatelet therapy is associated with an improved outcome in hospitalised patients with COVID-19: a propensity matched cohort study

Abstract

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 (TAC) 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, intensive care unit (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 four subgroups: Therapeutic anticoagulation (TAC), prophylactic anticoagulation+antiplatelet (PACAP), TAC+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 with PAC, TACAP and TAC were associated with less in-hospital all-cause mortality with an adjusted HR (aHR) of 0.113 (95% CI 0.028 to 0.449) and 0.126 (95% CI 0.028 to 0.528), respectively. The number needed to treat 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 to 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 TAC alone in hospitalised patients with COVID-19 was associated with a better outcome in comparison to PAC alone without an increase in the risk of major and minor bleeds. Sufficiently powered randomised controlled trials are needed to further evaluate the safety and efficacy of combining antiplatelet and anticoagulants agents or using TAC in the management of patients with COVID-19 infection.

Keywords: COVID-19; clinical; microvascular angina; pharmacology.

Figure 1

Flowchart of study participants.

Figure 2

Survival function for (A) invasive mechanical ventilation (B) all-cause mortality. Patients are stratified according to antithrombotic regimen used. (A) PACAP was associated with a decreased hazard for receiving invasive mechanical ventilation (aHR=0.070; 95% CI 0.014 to 0.351). (B) TACAP and TAC were associated with less in-hospital all-cause mortality with an aHR of 0.113 (95% CI 0.028 to 0.449) and 0.126 (95% CI 0.028 to 0.528), respectively. aHR, adjusted HR, PAC, prophylactic anticoagulation; PACAP, prophylactic anticoagulation+antiplatelet; TAC, therapeutic anticoagulation; TACAP, therapeutic anticoagulation+antiplatelet.