Efficacy and safety of increased doses of anticoagulants in COVID-19 patients: A systematic review and meta-analysis

Abstract

The aim of the study was to evaluate the efficacy and safety of increased doses of anticoagulants in comparison with standard doses in inpatients with COVID-19. A systematic review was carried out in October 2021 using the PubMed database. The analysis included only randomized clinical trials (RCTs) with ≥ 200 participants that reported the rate of death as the total number of cases or the percentage of patients. The primary outcome was all-cause mortality within the observational period. In addition, the risk of arterial and venous thrombotic events and major and clinically relevant nonmajor (CRNM) bleeding was assessed. Searching of Pubmed identified 8903 references. The final qualitative and quantitative analysis included the results of 6 RCTs that covered 5228 patients. Among all patients, 2660 received increased and 2568 standard doses of anticoagulants. The follow-up period varied from 21 to 30 days. The administration of increased doses did not affect the risk of death (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.73–1.25; I2 = 59.5%), was associated with a reduced risk of thrombotic events (OR, 0.56; 95% CI, 0.43–0.73; I2 = 20.6%), and increased risk of major bleeding (OR, 1.86; 95% CI, 1.23–2.80; I2 = 0%) or CRNM bleeding (OR, 3.65; 95% CI, 1.65–8.09; I2 = 0%). Within the sensitivity analysis, similar results were obtained in the subgroups of critically ill or stable patients and individuals with increased D-dimer. The maximal reduction in the risk of thrombotic events was found for the subgroup of patients with increased D-dimer (OR, 0.48; 95% CI, 0.32–0.70; I2 = 36.4%). The use of increased doses of anticoagulants in inpatients with COVID-19 does not reduce the risk of death. Still, it is associated with a decrease in the risk of thrombotic events and increased risk of major bleeding.

Keywords

• anticoagulation
• covid-19
• thrombosis
• treatment