Anticoagulant Treatment Regimens in Patients With Covid‐19: A Meta‐Analysis

Coronavirus disease 2019 (COVID‐19) is associated with a hypercoagulable state. It has been hypothesized that higher‐dose anticoagulation, including therapeutic‐dose and intermediate‐dose anticoagulation, is superior to prophylactic‐dose anticoagulation in the treatment of COVID‐19. This meta‐analysis evaluated the efficacy and safety of higher‐dose anticoagulation compared with prophylactic‐dose anticoagulation in patients with COVID‐19. Ten randomized controlled open‐label trials with a total of 5,753 patients were included. The risk of death and net adverse clinical events (including death, thromboembolic events, and major bleeding) were similar between higher‐dose and prophylactic‐dose anticoagulation (risk ratio (RR) 0.96, 95% CI, 0.79–1.16, P = 0.66 and RR 0.87, 95% CI, 0.73–1.03, P = 0.11, respectively). Higher‐dose anticoagulation, compared with prophylactic‐dose anticoagulation, decreased the risk of thromboembolic events (RR 0.63, 95% CI, 0.47–0.84, P = 0.002) but increased the risk of major bleeding (RR 1.76, 95% CI, 1.19–2.62, P = 0.005). The risk of death showed no statistically significant difference between higher‐dose anticoagulation and prophylactic‐dose anticoagulation in noncritically ill patients (RR 0.87, 95% CI, 0.50–1.52, P = 0.62) and in critically ill patients with COVID‐19 (RR 1.04, 95% CI, 0.93–1.17, P = 0.5). The risk of death was similar between therapeutic‐dose vs. prophylactic‐dose anticoagulation (RR 0.92, 95% CI 0.69–1.21, P = 0.54) and between intermediate‐dose vs. prophylactic‐dose anticoagulation (RR 1.01, 95% CI 0.63–1.61, P = 0.98). In patients with markedly increased d‐dimer levels, higher‐dose anticoagulation was also not associated with a decreased risk of death as compared with prophylactic‐dose anticoagulation (RR 0.86, 95% CI, 0.64–1.16, P = 0.34). Without any clear evidence of survival benefit, these findings do not support the routine use of therapeutic‐dose or intermediate‐dose anticoagulation in critically or noncritically ill patients with COVID‐19.