Efficacy and safety of therapeutic versus prophylactic dose of anticoagulation in hospitalized patients with severe COVID-19 pneumonia and coagulopathy: An open-label, randomized controlled trial

ABSTRACT

Background and Aims: The use of therapeutic anticoagulation to improve outcomes in COVID-19-associated coagulopathy remains unclear. We aimed to compare the efficacy and safety of therapeutic versus standard prophylactic anticoagulation in this population. Methods and Results: This was a single-center, open-label, two-arms, randomized controlled study conducted from 1st April to 15th July 2021. Two-hundred fifty severe COVID-19 patients with coagulopathy were randomly assigned (11 ratio) to receive either prophylactic anticoagulation (subcutaneous unfractionated heparin/UFH 5000IU b.i.d or fondaparinux 2.5mg o.d) or therapeutic anticoagulation (weightadjusted dose UFH or fondaparinux). Anticoagulation was administered until hospital discharge or at the treating physician's discretion. All patients received international COVID-19 guideline-driven therapy throughout the study. Baseline characteristics were not significantly different (p>0.05) between both arms, except for the Ddimer and CRP level at admission (p=0.04;p=0.001;respectively). During a 30-day follow-up, therapeutic arm revealed significant higher need for NIV/invasive MV (41.3% vs. 29%, p=0.02), higher progression to ARDS (34.1% vs. 16.1%, p=0.001), and increased 30-day all-cause mortality (58.7% vs. 15.3%, p<0.001) as compared with prophylactic arm. There was no significant difference between both arms in the incidence of acute MI (20% vs. 13.6%, p=0.07), VTE (4.8% vs. 0.8%, p=0.09), arterial thromboembolism (3.2% vs. 0%, p=0.29) and overall bleeding (17.6% vs. 6.4%, p=0.18) at 30-days. Conclusion: Therapeutic anticoagulation was considered safe and effective in preventing thromboembolic events, but not in the need for NIV/invasive MV, progression to ARDS and 30-day all-cause mortality in hospitalized patients with severe COVID-19 and coagulopathy.