579 The Efficacy and Safety of Andexanet Alfa in Patients With Acute Gastrointestinal Bleeding While Taking Factor Xa Inhibitors: An ANNEXA-4 Sub-Analysis

INTRODUCTION: Andexanet alfa is a recombinant modified human Factor Xa (FXa) decoy protein developed to reverse the anticoagulant effect of FXa inhibitors. METHODS: ANNEXA-4 was a prospective single-arm study of andexanet alfa in patients with acute major bleeding while taking a FXa inhibitor. Patients with major gastrointestinal (GI) bleeding were eligible if they had (1) signs/symptoms of hemodynamic compromise or (2) bleeding associated with a hemoglobin (Hb) drop ≥2 g/dL or baseline Hb ≤8 g/dL. Upon enrollment, patients were treated with one of two andexanet dosing regimens based on the type, timing, and dose of the most recent inhibitor intake. Efficacy was evaluated in all patients who met the bleeding criteria above and had a baseline anti-FXa activity ≥75 ng/mL (≥0.25 IU/mL for enoxaparin). Co-primary endpoints were the change in anti-FXa activity and the achievement of hemostasis, as adjudicated by an independent committee, at 12 hours after andexanet treatment. Hemostasis was defined as: excellent if the red blood cell transfusion-corrected Hb at 12 hours was ≤10% lower than baseline, good if Hb was 10-20% lower, and poor/none if Hb was >20% lower. RESULTS: Of 352 patients enrolled in the study, 90 had GI bleeding, of whom 62 were included in the efficacy analysis. Median age was 76 years (range 24-95); 51 (57%) were male. Patients were receiving rivaroxaban (n = 44), apixaban (n = 5), and edoxaban (n = 3) at study entry. Bleeding location was identified in 48 patients (upper n=27, lower n = 21) and unknown in 42 patients. 66 (73%) patients had some evidence of hemodynamic compromise, including 38 (42%) patients with hypotension. Mean Hb at the time of dosing was 4.9 ± 1.4 g/dL. In patients taking rivaroxaban, the baseline anti-FXa activity was 267 ± 168.5 ng/mL and the percent reduction with andexanet was 94% (95%CI 89-96). In apixaban patients, the baseline anti-FXa activity was 244 ± 215.0 ng/mL and the percent reduction with andexanet was 92% (95%CI 88-95). Excellent/good hemostasis was achieved in 85% of evaluable patients. 58 (94%) of 62 patients received red blood cell transfusions, 3 (5%) received platelet transfusion, and 2 (3%) received a coagulation factor product. 30-day rates of thrombosis and death were 6% and 13%, respectively. CONCLUSION: In patients with major GI bleeding treated with andexanet, a high rate of effective hemostasis was achieved. The thrombosis and mortality rates are consistent with prior studies in this patient population.

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