ANNEXA-4 Investigators
Andexanet alfa is a modified recombinant inactive form of factor Xa (FXa) that reverses FXa inhibitors. ANNEXA-4 was a cohort registration study evaluating andexanet in patients with acute major bleeding. We present the final data.
We evaluated 477 patients with acute major bleeding within 18 hours of FXa inhibitor administration. Co-primary outcomes were percent change in anti–FXa activity from baseline to nadir during andexanet treatment and percentage of patients with excellent or good hemostatic efficacy 12 hours after andexanet treatment.
Mean age was 78 years. Bleeding was predominantly intracranial (329 patients [69%]) or gastrointestinal (109 patients [23%]). In apixaban-treated patients (n=172), median anti–FXa activity decreased from 147 to 10 ng/mL (93% reduction; 95% CI, 94 -90%); in rivaroxaban-treated patients (n=130), it decreased from 214 to 11 ng/mL (94% reduction; 95% CI, 95-93%); in edoxaban-treated patients (n=28), median anti–FXa activity decreased from 121 to 24 ng/mL (71% reduction; 95% CI, 82- 65%); and in enoxaparin-treated patients (n=17), it decreased from 0.48 to 0.11 IU/mL (75% reduction; 95% CI, 79-67%). Excellent or good hemostasis occurred in 272 of 340 evaluable patients (80%, 95% CI 75-84%). Within 30 days, thrombotic events occurred in 50 patients (11%) and death in 81 patients (17%).
In acute major bleeding patients on FXa inhibitors, andexanet treatment reduced anti–FXa activity and resulted in good/excellent hemostasis in 80% of patients.
NCT02329327