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

Authors

Jordan M. Estroff, From the Center for Trauma and Critical Care, Department of Surgery (J.M.E., J.D., R.A., B.S.), George Washington University, Washington, DC; Trauma and Transfusion Medicine Research Center (L.H., A.H., M.D.N., J.B.B., L.L.), University of Pittsburgh Medical Center, Pittsburgh, PA; Department of Surgery (S.K., J.P.H.), Penn State Health Milton S. Hershey Medical Center; Department of Surgery (A.B.C., E.O.Y., J.N.), University of California, Irvine, Orange, CA; Ascension St. Vincent (L.E.J., J.W.), Indianapolis, IN; Department of Surgery (K.M.S.), Yale School of Medicine, New Haven, CT; Yale University/Yale New Haven Hospital (R.O'C.), New Haven, CT; Department of Surgery (G.R.S.), Wright State University Boonshoft School of Medicine, Dayton, OH; Miami Valley Hospital (A.D.S.), Dayton, OH; Maine Medical Center (D.C.), Portland, ME; Cooper University, Camden, NJ Grant Medical Center (T.E.), Columbus, OH; and OhioHealth Grant Medical Center (M.K., A.R.), Columbus, OH.
Joseph Devlin
Lara Hoteit
Adnan Hassoune
Matthew D. Neal
Joshua B. Brown
Liling Lu
Shannon Kotch
Joshua P. HazeltonFollow
Ashton B. Christian
Eric O. Yeates
Jeffry Nahmias
Lewis E. JacobsonFollow
Jamie Williams
Kevin M. SchusterFollow
Rick O'ConnorFollow
Gregory R. Semon
Angela D. Straughn
Daniel CullinaneFollow
Tanya EgodageFollow
Michelle KincaidFollow
Allison Rollins
Richard Amdur
Babak Sarani

Document Type

Article

Publication Title

The journal of trauma and acute care surgery

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.

First Page

541

Last Page

545

DOI

10.1097/TA.0000000000004345

Publication Date

10-1-2024

Recommended Citation

Estroff, Jordan M.; Devlin, Joseph; Hoteit, Lara; Hassoune, Adnan; Neal, Matthew D.; Brown, Joshua B.; Lu, Liling; Kotch, Shannon; Hazelton, Joshua P.; Christian, Ashton B.; Yeates, Eric O.; Nahmias, Jeffry; Jacobson, Lewis E.; Williams, Jamie; Schuster, Kevin M.; O'Connor, Rick; Semon, Gregory R.; Straughn, Angela D.; Cullinane, Daniel; Egodage, Tanya; Kincaid, Michelle; Rollins, Allison; Amdur, Richard; and Sarani, Babak, "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" (2024). Surgery. 17.
https://scholar.bridgeporthospital.org/surgery/17

Identifier

38685190 (pubmed); 10.1097/TA.0000000000004345 (doi); 01586154-990000000-00713 (pii)