Adverse Events in Bleeding Patients Treated With Andexanet Alfa or 4-Factor Prothrombin Complex Concentrate

Increasing use of factor Xa inhibitors (fXa-I) for preventing and treating thromboembolic events has been associated with increased bleeding events. However, the optimal reversal agent remains controversial. A recent RCT comparing Andexanet alpha (AA) and standard of care (mostly 4 factor prothrombin complex concentrate [4FPCC]) for treatment of patients on rivaroxaban or apixaban with an intracranial hemorrhage found better control of hematoma expansion with AA at the expense of a higher rate of thrombotic events, including ischemic stroke. We compared the rates of death and thrombotic events in AA and 4FPCC treated patients using real-world data.

This retrospective cohort study used the TriNetX Research Network. Patients aged 18 years or older who presented to the ED of 110 health care organizations with a life-threatening bleed (based on ICD-10 codes) who were on apixaban or rivaroxaban were included. Outcomes were death, stroke, myocardial infarction (MI), and venous thromboembolic (VTE) events within a 30-day period. Propensity score matching was used to control for demographic characteristics, pre-existing conditions, vital sign abnormalities, and type of FXa-I. Kaplan Meier survival analysis was also used to compare groups.

Ninety-one patients were treated with AA and 330 patients were treated with 4FPCC. After propensity matching there were 90 patients in each group. Groups were similar in baseline characteristics and comorbidities. Most patients were on apixaban, 66.2% in both groups. Unadjusted cumulative probabilities of death by 30 days were 22% and 17% in AA and 4FPCC treated patients, respectively, P=0.35. After matching, the probabilities of death were 12% in both groups. The unadjusted probabilities of stroke at 30 days were 9% and 12% in AA and 4FPCC treated patients, respectively, P=0.48. The unadjusted probabilities of MI were 7% and 5% in AA and 4FPCC treated patients, respectively, P=0.68. After propensity matching, the probabilities of VTE were 13% and 12% in AA and 4FPCC treated patients, respectively, P=0.22. Blood transfusion rates were also similar (28.9% in both groups).

This real-world, observational study found that after propensity matching, the 30-day outcomes including death, stroke, MI, VTE and blood transfusion were similar in fXa-I associated bleeding patients treated with AA and 4FPCC.