Therapeutic versus prophylactic anticoagulation in patients with COVID-19: a meta-analysis of randomised controlled trials

Abstract

Abstract Funding Acknowledgements Type of funding sources: None. Background Several systematic reviews and meta-analyses have been conducted to evaluate the effects of anticoagulation on patients admitted with coronavirus infectious disease 2019 (COVID-19). However, since most of them consist of observational studies, the optimal dose still remains controversial. Purpose The purpose of this study was to investigate the efficacy and safety of therapeutic anticoagulation compared with prophylactic anticoagulation in patients admitted with COVID-19. Methods A meta-analysis was conducted on randomised controlled trials (RCTs) to minimise bias. PubMed and the Cochrane Central Register of Controlled Trials were queried for the terms "covid-19," "(anticoagulation OR thromboprophylaxis)," and "randomised." The same terms or relevant studies were also queried on the website of the ClinicalTrials.gov and relevant reviews. The clinical endpoints of interest were all-cause death, thromboembolism, and major bleeding. Pooled estimates were calculated using a random-effects model. Results A total of 7 RCTs were included in this study. The risk of thromboembolism was lower (odds ratio (OR) 0.54; 95% confidence interval (CI) 0.41-0.73; p < 0.001) and the risk of major bleeding was higher (OR 1.87; 95% CI 1.21-2.90; p = 0.005) in the therapeutic anticoagulation group than in the prophylactic anticoagulation group. On the other hand, the risk of all-cause death was similar (OR 0.92; 95% CI 0.65-1.31; p = 0.65) between the 2 groups. In a subgroup analysis, the risk of thromboembolism was also lower in the therapeutic anticoagulation group compared with the prophylactic anticoagulation group both in moderately and severely ill patients, respectively. However, the risk of major bleeding was more likely to higher (OR 1.85; 95% CI 0.98-3.49; p = 0.06) in the therapeutic anticoagulation group than the prophylactic anticoagulation group only in severely ill patients. Conclusions Therapeutic anticoagulation is associated with a lower risk of thromboembolism and a higher risk of major bleeding compared to prophylactic anticoagulation in patients hospitalised with COVID-19. Therapeutic anticoagulation may be more beneficial for moderately ill patients.