Efficacy and safety of intensified versus standard prophylactic anticoagulation therapy in patients with Covid-19: a systematic review and meta-analysis

ABSTRACT

Objectives Randomised controlled trials (RCTs) have reported inconsistent effects from intensified anticoagulation on clinical outcomes in Covid-19. We performed an aggregate data meta-analysis from available trials to quantify effect on non-fatal and fatal outcomes and identify subgroups who may benefit. Methods We searched multiple databases for RCTs comparing intensified (intermediate or therapeutic dose) versus prophylactic anticoagulation in adults with laboratory-confirmed Covid-19 through 19 January 2022. We used random effects meta-analysis to estimate pooled risk ratios for mortality, thrombotic, and bleeding events (at end of follow-up or discharge) and performed subgroup analysis for clinical setting and dose of intensified anticoagulation. Results Eleven RCTs were included (n = 5873). Intensified versus prophylactic anticoagulation was not associated with a mortality reduction up to 45 days (relative risk (RR) 0.93;95%CI 0.79–1.10). There was a possible signal of mortality reduction for non-ICU patients, although with low precision and high heterogeneity (5 studies;RR 0.84;95% CI 0.49 - 1.44;I2 = 75%). Risk of venous thromboembolism was reduced (RR 0.53, 95%CI 0.41–0.69;I2 = 0%), with effect driven by therapeutic rather than intermediate dosing (interaction P = 0.04). Major bleeding was increased with intensified anticoagulation (RR 1.73, 95%CI 1.17–2.56) with no interaction for dosing and clinical setting. Conclusion Intensified anticoagulation has no effect on mortality among hospitalised adults with Covid-19 and is associated with increased bleeding risk. The observed reduction in venous thromboembolism risk and trend towards reduced mortality in non-ICU settings requires exploration in additional RCTs.