OC 31.2 - Andexanet Alfa Is Associated With Lower In-Hospital Mortality Compared To 4-Factor Prothrombin Complex Concentrate In Patients With Factor Xa Inhibitor–Related Major Bleeding

Monday, June 26, 2023

11:00 – 11:15 ET

Room: 516

Session Available As: Live-Stream and On-Demand

Presenting Author(s)

Paul P. Dobesh, PharmD, FACC, FAHA, FACC, BCPS, BCCP

Professor of Pharmacy Practice and Science
University of Nebraska Medical Center College of Pharmacy
Omaha, Nebraska, United States

Co-Author(s)

Craig I. Coleman, PharmD

Professor of Pharmacy Practice
University of Connecticut
Hartford, Connecticut, United States
MD

Mark Danese

President of Outcomes Insights, Inc.
Outcomes Insights
Agoura Hills, California, United States
MC

Mary J. Christoph

Director, Epidemiology, Medical & Payer Evidence
AstraZeneca Pharmaceuticals
Wilmington, Delaware, United States
EL

Eva Lesen

Director of Epidemiology at AstraZeneca
AstraZeneca
Gothenburg, Hallands Lan, Sweden
HC

Hungta Chen

Director, Medical & Payer Evidence Statistics
AstraZeneca Pharmaceuticals
Wilmington, Delaware, United States
JU

Julie Ulloa

Managing Partner, Outcomes Insights
Outcomes Insights
Agoura Hills, California, United States
SD

Sherry Danese

Vice President, Outcomes Insights
Outcomes Insights
Agoura Hills, California, United States
BK

Bruce Koch

Executive Director, Medical Affairs at Portola Pharmaceuticals
AstraZeneca
Wilmington, Delaware, United States
GF

Gregory J. Fermann

Professor of Emergency Medicine at University of Cincinnati
Department of Emergency Medicine, University of Cincinnati
Cincinnati, Ohio, United States

Background: Factor Xa inhibitors reduce the risk of ischemic events but carry an increased risk of major bleeding. Until andexanet alfa was approved in 2018, options for treating such bleeds were limited. Data comparing andexanet alfa versus 4-factor prothrombin complex concentrate (4F-PCC) in routine clinical practice are needed.

Aims: To compare in-hospital mortality in patients treated with either andexanet alfa or 4F-PCC while hospitalized for rivaroxaban- or apixaban-associated major bleeding.

Methods: This multicenter, observational study collected patient chart data from 354 US hospitals with andexanet alfa or 4F-PCC (or both) on formulary. Included patients were aged ≥18 years, treated with andexanet alfa or 4F-PCC during hospitalization for an anticoagulant-related major bleed (ICD-10 code D68.32, indicating bleeding due to extrinsic anticoagulants) between July 2018 and September 2022, received apixaban or rivaroxaban prior to hospitalization, and had a documented discharge disposition. In-hospital mortality for andexanet alfa versus 4F-PCC was compared via multivariable logistic regressions overall and by bleed location. The study was supported by AstraZeneca. An institutional review board waiver was obtained by Advarra Institutional Review Board Services, Inc., per US-HHS regulations; informed consent was not required.

Results: The Table presents characteristics of patients treated with andexanet alfa (n=2,122) or 4F-PCC (n=2,273). The two main bleed locations were gastrointestinal bleeds and intracranial hemorrhage (ICH). Overall, in-hospital mortality occurred in 6.0% of patients treated with andexanet alfa and in 10.6% of the 4F-PCC cohort. Patients treated with andexanet alfa had a 50% lower likelihood of in-hospital mortality compared to 4F-PCC (adjusted OR 0.50 [95% CI 0.38-0.65], p< 0.001). The risk reduction was similar in both gastrointestinal bleeds (52%) and ICH (46%); Figure.

Conclusion(s): Andexanet alfa was associated with a 50% lower likelihood of in-hospital mortality compared with 4F-PCC in patients with rivaroxaban- or apixaban-associated major bleeds. This result was similar in gastrointestinal bleeds and ICH.

Learning Objectives:

Upon completion, participants will be able to identfy the current landscape of treatment of oral factor Xa inhibitor related major bleeding
Upon completion, participants will be able to explain the methodology of this large real-world study evaluating differences in mortality between andexanet alfa and 4F-PCC for treatment of oral factor Xa inhibitor related major bleeding
Upon completion, participants will be able to discuss the results of a large real-world study evaluating differences in mortality between andexanet alfa and 4F-PCC for treatment of oral factor Xa inhibitor related major bleeding