Lower mortality with andexanet alfa vs 4-factor prothrombin complex concentrate for factor Xa inhibitor-related major bleeding in a U.S. hospital-based observational study

Paul P Dobesh; Gregory J Fermann; Mary J Christoph; Bruce Koch; Eva Lesén; Hungta Chen; Belinda Lovelace; Theresa Dettling; Mark Danese; Julie Ulloa; Sherry Danese; Craig I Coleman

doi:10.1016/j.rpth.2023.102192

Lower mortality with andexanet alfa vs 4-factor prothrombin complex concentrate for factor Xa inhibitor-related major bleeding in a U.S. hospital-based observational study

Res Pract Thromb Haemost. 2023 Aug 30;7(6):102192. doi: 10.1016/j.rpth.2023.102192. eCollection 2023 Aug.

Authors

Affiliations

¹ University of Nebraska Medical Center, College of Pharmacy, Omaha, Nebraska, USA.
² Department of Emergency Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
³ AstraZeneca, Wilmington, Delaware, USA.
⁴ AstraZeneca, Gothenburg, Sweden.
⁵ Outcomes Insights, Agoura Hills, California, USA.
⁶ University of Connecticut School of Pharmacy, Storrs, Connecticut, USA.
⁷ Evidence-based Practice Center, Hartford Hospital, Hartford, Connecticut, USA.

Abstract

Background: Well-designed studies with sufficient sample size comparing andexanet alfa vs 4-factor prothrombin complex concentrate (4F-PCC) in routine clinical practice to evaluate clinical outcomes are limited.

Objectives: To compare in-hospital mortality in patients hospitalized with rivaroxaban- or apixaban-related major bleeding who were treated with andexanet alfa or 4F-PCC.

Methods: An observational cohort study (ClinicalTrials.gov identifier: NCT05548777) was conducted using electronic health records between May 2018 and September 2022 from 354 U.S. hospitals. Inclusion criteria were age ≥18 years, inpatient admission with diagnosis code D68.32 (bleeding due to extrinsic anticoagulation), a record of use of the factor Xa inhibitors rivaroxaban or apixaban, andexanet alfa or 4F-PCC treatment during index hospitalization, and a documented discharge disposition. Multivariable logistic regression on in-hospital mortality with andexanet alfa vs 4F-PCC was performed. The robustness of the results was assessed via a supportive propensity score-weighted logistic regression.

Results: The analysis included 4395 patients (andexanet alfa, n = 2122; 4F-PCC, n = 2273). There were 1328 patients with intracranial hemorrhage (ICH), 2567 with gastrointestinal (GI) bleeds, and 500 with critical compartment or other bleed types. In the multivariable analysis, odds of in-hospital mortality were 50% lower for andexanet alfa vs 4F-PCC (odds ratio [OR], 0.50; 95% CI, 0.39-0.65; P < .01) and were consistent for both ICH (OR, 0.55; [0.39-0.76]; P < .01) and GI bleeds (OR, 0.49 [0.29-0.81]; P = .01). Similar results were obtained from the supporting propensity score-weighted logistic regression analyses.

Conclusion: In this large observational study, treatment with andexanet alfa in patients hospitalized with rivaroxaban- or apixaban-related major bleeds was associated with 50% lower odds of in-hospital mortality than 4F-PCC. The magnitude of the risk reduction was similar in ICH and GI bleeds.

Keywords: 4-factor prothrombin complex concentrate; andexanet alfa; anticoagulant reversal agents; cerebral hemorrhage; factor Xa inhibitors; gastrointestinal hemorrhage.

Associated data

ClinicalTrials.gov/NCT05548777