Four-factor prothrombin complex concentrate is not inferior to andexanet alfa for the reversal or oral factor Xa inhibitors: An Eastern Association for the Surgery of Trauma multicenter study

Abstract

BACKGROUND Andexanet alfa (AA) is the only FDA-approved reversal agent for apixaban and rivaroxaban (DOAC). There are no studies comparing its efficacy with four-factor prothrombin complex concentrate (PCC). This study aimed to compare PCC to AA for DOAC reversal, hypothesizing noninferiority of PCC. METHODS We performed a retrospective, noninferiority multicenter study of adult patients admitted from July 1, 2018, to December 31, 2019, who had taken a DOAC within 12 hours of injury, were transfused red blood cells (RBCs) or had traumatic brain injury, and received AA or PCC. Primary outcome was PRBC unit transfusion. Secondary outcome with intensive care unit length of stay. MICE imputation was used to account for missing data and zero-inflated Poisson regression was used to account for an excess of zero units of RBC transfused. Two units difference in RBC transfusion was selected as noninferior. RESULTS Results: From 263 patients at 10 centers, 77 (29%) received PCC and 186 (71%) AA. Patients had similar transfusion rates across reversal treatment groups (23.7% AA vs. 19.5% PCC) with median transfusion in both groups of 0 RBC. According to the Poisson component, PCC increases the amount of RBC transfusion by 1.02 times (95% confidence interval, 0.79-1.33) compared with AA after adjusting for other covariates. The average amount of RBC transfusion (nonzero group) is 6.13. Multiplying this number by the estimated rate ratio, PCC is estimated to have an increase RBC transfusion by 0.123 (95% confidence interval, 0.53-2.02) units compared with AA. CONCLUSION PCC appears noninferior to AA for reversal of DOACs for RBC transfusion in traumatically injured patients. Additional prospective, randomized trials are necessary to compare PCC and AA for the treatment of hemorrhage in injured patients on DOACs. LEVEL OF EVIDENCE Therapeutic/Care Management; Level III.