The effect of higher-intensity dosing of anticoagulation on the clinical outcomes in hospitalized patients with COVID-19: A meta-analysis of randomized controlled trials

We aimed to perform a meta-analysis to summarize the overall evidence from randomized controlled trials related to higher-intensity anticoagulation in hospitalized patients with COVID-19. A systematic literature search was performed in electronic databases to identify randomized controlled trials comparing the clinical outcomes between intermediate/ therapeutic anticoagulation and prophylactic anticoagulation. Meta-analyses with random-effects models were used to estimate the pooled odds ratio (OR) for outcomes of interest at a 95% confidence interval (CI). Eight randomized controlled trials were included, with a total of 5405 hospitalized patients with COVID-19. The meta-analysis revealed no statistically significant difference in the odds of mortality (pooled OR = 0.92; 95% CI 0.71–1.19) but a statistically significant reduction in the odds of development of thrombotic events (pooled OR = 0.55; 95% CI 0.42–0.72), and significantly increased odds of development of major bleeding (pooled OR = 1.81; 95% CI 1.20–2.72) with the use of intermediate/therapeutic anticoagulation, relative to prophylactic anticoagulation. Subgroup analysis in patients with a severe course of COVID-19 observed a statistically significant reduction in the odds of development of thrombotic events (pooled OR = 0.66; 95% CI 0.45–0.98) but no significant difference in the odds of development of major bleeding events (pooled OR = 1.37; 95% CI 0.74–2.56), with the use of intermediate/therapeutic anticoagulation, relative to prophylactic anticoagulation. There could be net clinical benefits with higher-intensity dosing of anticoagulation relative to prophylactic-dosing of anticoagulation among hospitalized patients with severe COVID-19.