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Andexanet Alfa for Factor Xa Inhibitor-Associated Bleeding
Study Questions:
How effective is andexanet alfa at controlling major bleeding associated with factor Xa inhibitor use?
Methods:
The authors studied 352 patients with acute major bleeding within 18 hours after administration of factor Xa inhibitor therapy. The co-primary endpoints were the percent change in anti–factor Xa activity and the percent of patients with excellent or good hemostatic efficacy at 12 hours following andexanet alfa infusion. A subgroup analysis was performed on patients with confirmed major bleeding and a baseline anti–factor Xa activity of ≥75 ng/ml.
Results:
Patients in the study were of mean age 77 years. Bleeding events were largely intracranial (227 patients [64%]) or gastrointestinal (90 patients [26%]). Anti–Xa activity was reduced by a mean of 92% (95% confidence interval [CI], 91-93%) in apixaban-treated patients and 92% (95% CI, 88-94%) in rivaroxaban-treated patients. Excellent or good hemostasis occurred in 204/249 (82%) patients who could be evaluated. Death within 30 days occurred in 49 (14%) patients and a thrombotic event occurred in 34 (10%) patients.
Conclusions:
The authors concluded that among patients with acute major bleeding associated with anti–factor Xa medications (primarily apixaban and rivaroxaban), anti–Xa activity was significantly reduced and good or excellent hemostasis was achieved by 12 hours in the vast majority of patients.
Perspective:
This publication expands on the interim report from 2015 (N Engl J Med 2015;373:2413-24) on the safety and efficacy of andexanet alfa treatment for patients with major bleeding following recent factor Xa inhibitor use. Based largely on that publication, the Food and Drug Administration already approved andexanet alfa in 2018. Implementation of this medication has been challenging at many centers, given the low drug supply nationally and the relatively high price tag. It should be noted that efficacy data for andexanet alfa is limited to patients with intracranial hemorrhage or major gastrointestinal bleeding and does not include patients presenting without bleeding but who require emergent surgery. Individual health centers should develop protocols for management of bleeding associated with direct oral anticoagulants, so that the most appropriate therapy (andexanet alfa for factor Xa inhibitors, idarucizumab for dabigatran, and prothrombin complex concentrates for warfarin or when andexanet alfa is not available/indicated) can be rapidly and appropriately selected along with the correct dose for administration. A stewardship program is also warranted to ensure that only patients with life-threatening bleeding events are treated with these reversal medications, given both the potential for prothrombotic effects and the high administration cost. Importantly, all patients who experienced thrombotic events in this study did so before anticoagulation was resumed. Therefore, anticoagulation should be resumed as soon as is safe to prevent future thrombotic events.
Clinical Topics: Anticoagulation Management, Dyslipidemia, Geriatric Cardiology, Prevention, Lipid Metabolism, Novel Agents
Keywords: Anticoagulants, Blood Coagulation Factors, Factor Xa, Factor Xa Inhibitors, Geriatrics, Hemorrhage, Hemostasis, Hemostatics, Intracranial Hemorrhages, Secondary Prevention, Thrombosis, Warfarin
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