Therapeutic Versus Non‐Therapeutic Dose Anticoagulation in COVID‐19 Infection: A Systematic Review and Meta‐analysis of Randomised Controlled Trials

Background: Abnormal coagulation and thrombotic complications prompted many guidelines to recommend thromboprophylaxis for patients hospitalised with COVID‐19, but the dose required for prophylaxis remains unclear. This systematic review (SR) analyses the safety and efficacy of therapeutic dose anticoagulation (TDA) versus non‐therapeutic dose anticoagulation (NDA) in COVID‐19 patients. Methods: According to the Cochrane Handbook of Systematic Review of Interventions, we performed an SR. The protocol is registered in Prospero (CRD42021269197, date 12 August 2021). Results: In this SR of 18 studies, TDA was shown to reduce all‐cause mortality (risk ratio [RR] 0.83; 95% confidence interval [95% CI] 0.70, 0.99) in COVID‐19 infection. TDA also reduced thrombosis (RR 0.55; 95% CI 0.48, 0.72) but increased major bleeding (RR 1.87; 95% CI 1.29, 2.69). A stratified analysis according to severity revealed that, in non‐critical patients, TDA resulted in mortality benefit (RR 0.79; 95% CI 0.67, 0.94). In critical patients, TDA did not affect all‐cause mortality (RR 1.03; 95% CI 0.89, 1.18) but reduced thrombosis (RR 0.65; 95% CI 0.48, 0.86) and increased major bleeding (RR 1.85; 95% CI 1.06, 3.23). Conclusion: TDA significantly reduced all‐cause mortality and thrombosis in non‐critical COVID‐19 patients at the expense of increased major bleeding. In critical COVID‐19, this mortality benefit was not observed.