Safety and efficacy of antithrombotics in outpatients with symptomatic COVID-19: A systematic review and meta-analysis

Background: Coronavirus disease (COVID-19) is a global health emergency, with well over six hundred million infections and over six million deaths to date. Besides other ramifications, it is also associated with inflammation and an augmented risk of thromboembolic complications. Despite this, the risks and benefits of antithrombotic drugs in patients with mild to moderate COVID-19 have not been well-established and remain controversial. Objectives: To evaluate the safety and efficacy of antithrombotic drugs on mild to moderate symptomatic COVID-19 patients by performing an updated systematic review and meta-analysis. Methods: We queried electronic databases (PubMed, Cochrane Central, Scopus, and Embase) from their inception up to September 2022 for randomized controlled trials comparing antithrombotic drugs against placebo. The outcomes of interest were the need for hospital care, mortality, and thromboembolic events in the enrolled participants. Dichotomous outcomes were presented as risk ratio (RR) with 95 % confidence intervals (CIs) and were consolidated using random-effects model. Main Results: Five eligible studies (Rivaroxaban/Apixaban, two; enoxaparin, two; Sulodexide, one), consisting of 2,005 participants with mild to moderate COVID-19, were included. Pooled results show that antithrombotics, when compared to placebo, do not significantly reduce allcause mortality (RR 0.51, 95 % CI 0.15-1.68; P = 0.27; I2 = 0), thromboembolic events (RR 0.78, 95 % CI 0.17-3.51; P = 0.74; I2 = 0), need for hospitalization (RR 0.73, 95 % CI 0.51-1.03; P = 0.08; I2 = 0), nor significantly increase clinically relevant non-major bleeding events (RR 2.36, 95 % CI 0.56-9.89; P = 0.24; I2 = 0). However, when Sulodexide was compared independently to other antithrombotics, it significantly reduced the need for hospitalization (RR 0.60, 95 % CI 0.37-0.95; P = 0.03).