Safety and Efficacy of Apixaban For Therapeutic Anticoagulation in Critically Ill ICU Patients with Severe COVID-19 Respiratory Disease

Abstract

Introduction Despite the use of unfractionated heparin (UFH) or low molecular weight heparin (LMWH), rates of thromboembolic disease, and subsequent morbidity and mortality remain unacceptably high in patients with severe novel coronavirus disease 2019 (COVID-19) disease. Direct oral anticoagulants (DOACs), such as apixaban, have numerous purported benefits although the safety and efficacy of their use in intensive care unit (ICU) patients with severe COVID-19 has yet to be evaluated. Materials and Methods Single-center, retrospective cohort study of 21 ICU patients with severe COVID-19 respiratory disease treated with apixaban for atrial fibrillation (AFib), venous thromboembolism (VTE), catheter-induced thrombosis, and/or COVID-19-induced coagulopathy. The primary objective was to evaluate the incidence of bleeding events and secondary objectives included thromboembolic events, coagulation parameters, and mortality. Results Ninety percent of patients were non-White, 43% were obese, 90% had acute respiratory distress syndrome, and 76% required mechanical ventilation. Nearly half of (47.6%) also experienced renal dysfunction and required renal replacement therapy. Eighty-six percent of patients received prophylaxis or treatment with UFH or LMWH within the 24-hour period prior to apixaban initiation. Patients were initiated on apixaban for the treatment of suspected or confirmed VTE (67%) or AFib (33%). All coagulation parameters remained abnormal but stable throughout the 10-day monitoring period. No patients experienced any major bleeding events or thrombosis throughout the study period. There were four deaths during the follow-up period, all deemed unrelated to coagulopathy or bleeding. Conclusion Apixaban appeared safe and efficacious in ICU patients with severe COVID-19 disease. These data encourage future trials seeking to optimize anticoagulation strategies in patients with severe COVID-19.

Keywords: COVID-19; SARS-CoV-2; apixaban; coagulopathy; thrombosis.

Fig. 1

Adapted institutional anticoagulation guideline for the management of COVID-19-induced coagulopathy in ICU patients. AKI, acute kidney injury; aPTT, activated partial thromboplastin time; COVID-19, novel coronavirus disease 2019; DIC, disseminated intravascular coagulation; DOAC, direct oral anticoagulant; SIC, SIC, sepsis-induced coagulopathy; UFH, unfractionated heparin; VTE, venous thromboembolism.

Fig. 2

Select coagulation parameters measured over 10 days from the initiation of apixaban in ICU patients with COVID-19. Mean values are displayed with error bars representing standard deviations. aPTT, activated partial thromboplastin time; COVID-19, novel coronavirus disease 2019; ICU, intensive care unit; INR, international normalized ratio; PT, prothrombin time.