Therapeutic-dose anticoagulation or thromboprophylaxis with low-molecular-weight heparin for moderate Covid-19: meta-analysis of randomized controlled trials

We carried out a meta-analysis since there is not enough evidence to recommend for or against therapeutic-dose anticoagulation compared with thromboprophylaxis in noncritically ill patients hospitalized with Covid-19. We performed a systematic literature search using PubMed, Embase, Cochrane Library, and MedRxiv for randomized trials that included therapeutic-dose with low-molecular-weight heparin (LMW) or thromboprophylaxis with LMW heparin in noncritically ill patients admitted to the hospital with Covid-19. We identified five open-label studies for analysis with a total of 3220 patients. Two independent researchers selected, assessed, and extracted the data in duplicate. The outcomes evaluated were all-cause mortality, progression to invasive mechanical ventilation, incidence of venous thromboembolism, and major bleeding. The studies did not show risk for selection, detection, attrition, or reporting bias. Therapeutic-dose anticoagulation with LMW heparin compared with thromboprophylaxis with LMW heparin had no significant effect of all-cause death (risk ratio [RR] 0.85; 95% confidence interval [CI] 0.67–1.07; P = 0.16; I2 = 48%), or progression to invasive mechanical ventilation (RR 0.89; CI 0.73–1.08; P = 0.24; I2: 0%). Therapeutic-dose anticoagulation significantly reduced the risk of venous thromboembolic disease (RR 0.42; 95% CI 0.28–0.62; P = 0.0001; I2 = 0%) [Number needed to treat = 37]. Major bleeding occurred in 1.79% of the patients receiving therapeutic-dose anticoagulation and in 0.97% of those receiving thromboprophylaxis [Number needed to harm 125]. Therapeutic-dose anticoagulation in noncritically ill patients with Covid-19 could be indicated for patients at high risk of venous thromboembolic disease and low risk of bleeding.