Efficacy and Safety of Activated Prothrombin Complex Concentrate for Reversal of the Anticoagulant Effect of Apixaban and Rivaroxaban in Patients with Major Bleeding.

Abstract

The use of activated prothrombin complex concentrate (aPCC) to treat direct oral anticoagulant (DOAC)-associated bleeding is off-label and clinical experience is limited. We aimed to assess the efficacy and safety of aPCC in reversing the anticoagulant effect of apixaban and rivaroxaban in patients presenting with major bleeding. A retrospective cohort study of adult non-randomized patients was conducted at a tertiary referral medical center in the United States (US) to investigate the use of aPCC for the reversal of the anticoagulant effect of apixaban and rivaroxaban in patients presenting with major bleeding. The primary outcome was achieving clinical hemostasis according to prespecified criteria. Safety outcomes included the occurrence of thrombotic events during hospitalization. A total of 217 patients were included in the study. Intracranial hemorrhage (ICH) was the most common site of bleeding (n = 100, 46.1%), followed by gastrointestinal bleed (n = 87, 40.1%). Clinical hemostasis was achieved in 170 patients (78.3%), and the risk of not achieving hemostasis with ICH-related bleeding was significantly higher than that of non-ICH-related bleeding (2.5, 95% confidence interval [CI] 1.44-4.34; p < 0.001). Eight patients not achieving hemostasis died during hospitalization, all of whom were suffering from ICH, and mortality associated with non-ICH-related bleeding was significantly lower compared with ICH-related bleeding (0.91, 95% CI 0.86-0.97; p < 0.001). Thromboembolic events during hospitalization occurred in one patient (0.5%). The use of aPCC for the management of apixaban- or rivaroxaban-related major bleeding is effective in most cases and is associated with a low risk of thromboembolism.