Clinical Pathways and Outcomes of Andexanet Alfa Administration for the Reversal of Critical Bleeding in Patients on Oral Direct Factor Xa Inhibitors.

ABSTRACT

Background Andexanet is U.S. Food and Drug Administration (FDA) approved for the reversal of critical bleeding from factor Xa inhibitors and off-label for surgical reversal. Data are lacking on andexanet administration processes. Methods We retrospectively studied patients at a 23-hospital system who received andexanet from November 2019 to March 2023. Abstractors coded demographics, comorbidities, anticoagulant use, andexanet indication, and process times. The primary outcome was presentation-to-andexanet time; diagnosis, ordering, and administration times were calculated. Secondary outcomes included in-hospital postandexanet major thromboembolism/bleeding and mortality. Results In total, 141 patients were analyzed. Andexanet indications were predominantly neurologic bleeding (85.8%). Twenty-four patients (17.0%) were transferred from nontertiary/academic centers to tertiary/academic centers. The median presentation-to-administration time was 192.5 minutes (interquartile range [IQR] 108.0-337.0 minutes). Components were as follows 72.5 minutes (IQR 39.0-137.5 minutes) for bleeding diagnosis; 35.5 minutes (IQR 0-96.5 minutes) for andexanet ordering; and 53.0 minutes (IQR 38.5-78.5 minutes) for administration, which was longer at tertiary/academic hospitals (ratio 1.5, 95% confidence interval [CI] 1.2-2.0, p = 0.002). Gastrointestinal or other critical bleeding (ratio 2.59, 95% CI 1.67-4.02, p < 0.001), and tertiary/academic center treatment (ratio 1.58, 95% CI 1.15-2.18, p = 0.005), were associated with increased time. Major thromboembolism, bleeding, and mortality occurred in 10.6, 12.0, and 22.9% of patients, respectively. Conclusions In our cohort, the median presentation-to-administration time was over 3 hours. Cumulative times were longer at tertiary/academic hospitals and for gastrointestinal/other bleeding. Postandexanet major thromboembolism/bleeding occurred more at tertiary/academic hospitals, possibly related to transfers. Prospective studies may elucidate clinical decision-making bottlenecks.