Appropriate thromboprophylaxis strategy for COVID-19 patients on dosage, antiplatelet therapy, outpatient and post-discharge prophylaxis: a meta-analysis of randomized controlled trials

Background: There was controversy surrounding the optimal thromboprophylaxis strategy for COVID-19 patients. This included debates on the dosage of anticoagulants for thromboembolism prophylaxis, the requirement for additional antiplatelet therapy, and the necessity of prophylaxis for outpatients and post-discharge. To explore this, we performed a meta-analysis of randomized controlled trials. Methods: PubMed, Cochrane Library, Embase, and Web of Science were last searched on 26 July 2023 for studies comparing the effect of different dose of anticoagulation, additional antiplatelet and post-discharge prophylaxis for COVID-19 patients. The results of eligible studies were analyzed in terms of thromboembolism events, major bleeding and all-cause mortality during follow-up. Results: Our study included a total of 25 randomized controlled trials, involving 17,911 patients. Our results revealed that, compared to prophylactic dose, therapeutic dose showed lower thrombotic risk (RR, 0.66; 95%CI, 0.45 to 0.96) but had similar major bleeding risk for critically ill patients with COVID-19. On the other hand, intermediate dose and prophylactic dose demonstrated similar thromboembolism risk and major bleeding risk. For non-critically ill patients with COVID-19, therapeutic dose of anticoagulants was associated with lower thrombotic risk (RR, 0.50; 95%CI 0.34 to 0.72) but, at the same time, increased the risk of major bleeding (RR, 2.01; 95%CI 1.22 to 3.33). However, intermediate dose showed lower thromboembolism risk (RR, 0.38; 95%CI 0.21 to 0.69) while maintaining a similar major bleeding risk. In critically ill patients, additional antiplatelet therapy showed similar thromboembolism, major bleeding risk, and mortality when compared to no treatment. For outpatients, additional prophylactic anticoagulation showed similar thromboembolism, major bleeding risk, and mortality when compared to no treatment. For post-discharge patients, post-discharge prophylaxis reduced thromboembolism risk (RR, 0.49; 95%CI 0.31 to 0.76) but increased major bleeding risk (RR, 2.63; 95%CI, 1.13 to 6.14). Conclusion: For non-critically ill patients, therapeutic dose prophylactic anticoagulation significantly reduced venous thromboembolism but increases major bleeding risk. Intermediate dose effectively lowered venous thromboembolism without raising major bleeding risk. The optimal dose and need for additional antiplatelet therapy in critically ill patients, as well as the necessity of prophylactic anticoagulation in outpatient and post-discharge patients, required further investigation and confirmation through rigorous evidence studies.