Primary Thromboprophylaxis in Ambulatory Symptomatic Patients with COVID-19: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background:The global impact of the COVID-19 pandemic has prompted the search for strategies to improve outcomes in affected individuals, including those initially managed in outpatient settings. Thromboembolic events have been reported as a concerning complication. Objectives:The aim of this study was to evaluate efficacy and safety of primary thromboprophylaxis in outpatients with COVID-19. The study protocol was registered in PROSPERO (CRD42022362776). Methods:The study adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and conducted a comprehensive search of PubMed/MEDLINE, ClinicalTrials.gov, and OVID/Embase and CENTRAL from Cochrane for studies up to December 11, 2023, without language restrictions. Randomized controlled trials comparing prophylactic-dose anticoagulation with placebo or standard of care in symptomatic outpatients with COVID-19 were included in this analysis. The primary outcome was the composite of all-cause hospitalization and death within 30 days. Secondary outcomes included venous thromboembolism, the composite of venous thromboembolism and major arterial cardiovascular events, and the individual components of the primary outcome. Results:Seven randomized controlled trials and 3758 COVID-19 outpatients were included. When compared with placebo or standard of care, thromboprophylaxis was associated with similar rates of all-cause hospitalization or mortality (relative risk, 1.00; 95% CI, 0.77-1.31) and lower rates of venous thromboembolism (relative risk, 0.28; 95% CI, 0.08-0.94), corresponding to a 0.6% absolute risk reduction and number needed to treat of 174. Conclusion:Thromboprophylaxis in symptomatic COVID-19 outpatients led to reduction in venous thromboembolism risk, with no impact on hospitalization or death. However, the overall low absolute risk reduction may not support its routine use.