Efficacy and safety of escalated versus standard prophylactic anticoagulation in patients with Covid-19: A literature review and meta-analysis

Abstract

Background: Coronavirus disease 2019 (COVID-19) is known to increase the risk of venous thromboembolism (VTE), and studies have shown a three-fold increase in VTE-risk in hospitalized COVID-19 patients compared to similar respiratory infections. Standard dose thromboprophylaxis is recommended in all hospitalized COVID-19 patients. However, despite prophylaxis, VTE incidence remains high. Several randomized controlled trials (RCTs) have studied the effect of escalated doses of thromboprophylaxis, but they have produced conflicting results, and have not been adequately powered to assess the outcomes VTE, major bleeding and all-cause mortality.

Aim: To conduct a literature review and meta-analysis of RCTs, comparing the effect of escalated versus standard doses of prophylactic anticoagulation in hospitalized COVID-19 patients admitted to an intensive care unit (ICU) or non-ICU, focusing on VTE, major bleeding and all-cause mortality.

Methods: A structured literature search was performed to retrieve RCTs investigating the safety and efficacy of escalated versus standard doses of prophylactic anticoagulation in hospitalized COVID-19-patients. The trials were analyzed in overall populations, and subgroups based on clinical setting (ICU/non-ICU). Risk ratios (RRs) with 95% Confidence intervals (95% CI) for VTE, death and major bleeding were extracted, and pooled results were calculated and displayed in forest plots.

Results: In the meta-analysis, 9 RCTs were included (n=5,658). Compared to standard dose, escalated dose prophylactic anticoagulation was associated with an overall reduction in VTE risk (RR: 0.49, 95% CI: 0.38-0.64), an increase in major bleeding risk (RR: 1.76, 95% CI: 1.19-2.59) and no difference in mortality (RR: 0.98, 95% CI: 0.88-1.09). In subgroup analysis based on clinical setting, estimates indicated a further reduction in VTE risk and all-cause mortality in non-ICU-patients compared to ICU-patients. However, these differences did not reach statistical significance.

Conclusion: Escalated doses of prophylactic anticoagulation was associated with a reduction in VTE-risk, increased major bleeding and no effect on all-cause mortality.