Anticoagulation therapy in hospitalized patients with COVID-19: a meta-analysis of randomized clinical trials.

Thromboembolic events are common in hospitalized patients with COVID-19, suggesting that SARS-CoV-2 infection may be related to a prothrombotic state. Several clinical trials evaluating different anticoagulation strategies were developed. Thus, we proposed conducting a meta-analysis of randomized clinical trials that evaluated the efficacy and safety of therapeutic anticoagulation with heparins in hospitalized patients with COVID-19. We searched PubMed, Cochrane, and Epistemonikos for studies published until December 22, 2022. Nine studies compared prophylactic/intermediate anticoagulation versus therapeutic anticoagulation with heparins were included. Four efficacy and one safety endpoints were analyzed: all-cause mortality, thromboembolic events, pulmonary embolism, need of intensive care unit or non-invasive ventilation, and major bleeding. Compared with prophylactic/intermediate anticoagulation, therapeutic anticoagulation with heparins was not associated with a reduction in all-cause mortality and need of intensive care unit or non-invasive ventilation in hospitalized patients with COVID-19, but showed a reduction in the number of thromboembolic events (RR 0.54, 95% CI 0.41-0.71, I2 = 0 %) and pulmonary embolisms (RR 0.37, 95% CI 0.24-0.57, I2 = 0 %), besides an increase in major bleeding (RR 1.67, 95% CI 1.05-2.64, I2 = 0 %). This meta-analysis did not show a reduction in all-cause mortality in hospitalized patients with COVID-19 who received anticoagulation with heparin at a therapeutic dose compared to those who received a prophylactic/intermediate dose, as well as no significant differences were found in the need of intensive care unit admission or use of non-invasive ventilation. There was, however, a reduction in thromboembolic events, pulmonary embolism, and increased bleeding (Tab. 1, Fig. 5, Ref. 31). Keywords: COVID-19, anticoagulation, heparins, meta-analysis.