Thromboprophylaxis After COVID-19 Hospitalization

Quick Takes

  • COVID-19–related hospitalizations and associated risks of thromboembolism are relatively low.
  • Use of prophylactic-dose apixaban did not reduce the risk of death or thromboembolism following COVID-19–related hospitalization.
  • Use of prophylactic-dose apixaban was associated with a low risk of bleeding when used following hospitalization for COVID-19.

Study Questions:

Is anticoagulation superior to placebo in reducing the risk of death and thromboembolic complications after hospital discharge for coronavirus disease 2019 (COVID-19) infection?


The ACTIV-4C (COVID-19 Thrombosis Prevention Trials: Post-hospital Thromboprophylaxis) investigators conducted a randomized, double-blind, placebo-controlled clinical trial between 2021–2022 in 127 US hospitals. Adult patients aged ≥18 years who were hospitalized for ≥48 hours for COVID-19 infection were eligible for inclusion. Patients were randomized prior to discharge to apixaban 2.5 mg twice daily or placebo for 30 days. The primary outcome was 30-day composite of death, arterial thromboembolism, and venous thromboembolism. The primary safety outcomes were 30-day major bleeding and clinically relevant nonmajor bleeding.


The trial was terminated early after 1,217 patients were randomized due to a lower than expected event rate and a declining rate of COVID-19 hospitalization. The mean age was 54 years and 50.4% were women, 26.5% were Black, and 16.7% were Hispanic. The primary composite endpoint occurred in 2.13% (95% confidence interval [CI], 1.14%-3.62%) of patients randomized to apixaban and 2.31% (95% CI, 1.27%-3.84%) randomized to placebo (relative risk, 0.92; 95% CI, 0.44-1.95). Major bleeding occurred in two (0.4%) patients in the apixaban arm and one (0.2%) patient in the placebo arm. Clinically relevant nonmajor bleeding occurred in three (0.6%) patients in the apixaban arm and six (1.1%) patients in the placebo arm.


The authors concluded that the incidence of death or thromboembolism following hospitalization for COVID-19 was low.


While the early waves of the COVID-19 pandemic were associated with high rates of both hospitalization and hospital-associated thrombosis (venous and arterial), subsequent waves have required lower rates of hospitalization and been associated with lower risks of thromboembolism. This National Institutes of Health–sponsored study demonstrates that in the current era of COVID-19 infection, routine use of post-hospital thromboprophylaxis is not needed given the relatively low event rates. At the same time, the study found very low rates of bleeding associated with prophylactic-dose apixaban, numerically similar to placebo.

Clinical Topics: Anticoagulation Management, COVID-19 Hub, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Anticoagulation Management and Venothromboembolism

Keywords: Anticoagulants, COVID-19, Hemorrhage, Hospitalization, Pandemics, Patient Discharge, Risk, Secondary Prevention, Thromboembolism, Thrombosis, Vascular Diseases, Venous Thromboembolism

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