(1004) Comparison of Reversal Agents for Direct Oral Anticoagulant-Associated Life-Threatening Bleeds

Introduction: Current treatment strategies for direct oral anticoagulant (DOAC)-associated life-threatening bleeds include both andexanet alfa and four-factor prothrombin complex concentrate (4FPCC), however the preferred agent remains debated. Recent literature suggests andexanet alfa results in better control of intracerebral hematoma expansion although associated with serious thrombotic complications. This study aims to compare the effectiveness, time to administration, mortality, and rate of thromboembolism between the two agents.

Methods: This was a single-center, retrospective, cohort study that included adult patients hospitalized at a large academic medical center. Patients had to be 19 years of age or older with confirmed receipt of an anti-Xa inhibitor prior to presentation. Patients must have received either 4FPCC or andexanet alfa for the indications of intracranial hemorrhage or gastrointestinal bleed. The primary outcome was hemostatic control, defined according to the International Society on Thrombosis and Hemostasis (ISTH) criteria. Patients were matched by age (+/- 5 years) and Glasgow Coma Score severity. Chi squared tests were utilized for categorical data and T-tests were utilized for continuous data.

Results: In total, 36 andexanet alfa and 36 4FPCC patients were included in the analysis. The majority of patients received anticoagulant reversal for intracranial hemorrhage followed by a subset in the 4FPCC group for gastrointestinal bleed. Hemostatic control was achieved in 27 patients in the andexanet alfa group compared to 16 in the 4FPCC group (75% vs. 44%; p= 0.01). There was no statistical difference in mortality or length of stay between groups. Although not statistically significant, the rate of thromboembolism was three times higher in the andexanet alfa group (25% vs. 8%; p= 0.06). Notably, time to administration was significantly faster in the 4FPCC group (64 min [38-81] vs. 89 min [74-106]; p= 0.04).

Conclusions: Andexanet alfa may be associated with increased rates of effective hemostatic control. However, there was no difference in mortality or length of stay between groups. Andexanet alfa was associated with longer times to administration and demonstrated a trend toward increased rates of thromboembolism although this finding was not statistically significant.