Reversal of apixaban and rivaroxaban with andexanet alfa prior to invasive or surgical procedures

• Published in: Pharmacotherapy Vol. 42; no. 10; pp. 780 - 791
• Main Authors: Bradshaw, Paige Garber, Keegan, Shaun Patrick, Droege, Molly Elizabeth, Dykes, Nicole Jade Harger, Ernst, Neil Edward, Foertsch, Madeline Jane, Makley, Amy Teres, Mueller, Eric William, Philpott, Carolyn Dosen, Srinivasan, Vasisht, Winter, Jessica Brooke, Goodman, Michael D., Droege, Christopher Allen
• Format: Journal Article
• Language: English
• Published: United States 01.10.2022
• Subjects: anticoagulation reversal; anticoagulation reversal agents; factor Xa; Factor Xa - therapeutic use; factor Xa inhibitors; Factor Xa Inhibitors - adverse effects; general surgery; Hemorrhage - chemically induced; Hemorrhage - prevention & control; Hemostatics - therapeutic use; Humans; Pyrazoles - adverse effects; Pyridones - adverse effects; recombinant proteins; Recombinant Proteins - therapeutic use; Retrospective Studies; Rivaroxaban - adverse effects; general surgery; recombinant proteins; factor Xa; factor Xa inhibitors; anticoagulation reversal agents; anticoagulation reversal
• ISSN: 0277-0008; 1875-9114
• DOI: 10.1002/phar.2727

Background Outcomes following andexanet alfa reversal of factor Xa inhibitors in patients requiring urgent or emergent invasive procedures are lacking. This study aimed to describe efficacy and safety outcomes following andexanet alfa administration within 24 h of an invasive procedure. Methods This single‐center, observational, retrospective study included patients who received andexanet alfa within 24 h of an invasive or surgical procedure. The primary outcome was hemostatic efficacy graded as excellent, good, or poor using similar definitions to the ANNEXA‐4 criteria. Secondary outcomes included hospital discharge disposition, intensive care unit (ICU) and hospital length of stay, 30‐day mortality, 30‐day thromboischemic event rates, and serum coagulation assay changes pre‐ and postreversal. Results Forty‐four patients met inclusion criteria; of these, 27 (62.8%) received apixaban and 16 (37.2%) were treated with rivaroxaban prior to admission. The indications for reversal were categorized as intracranial (n = 20 [45.5%]) or extracranial (n = 24 [54.5%]) sites. Majority of patients required emergent operative procedures (18 [40.9%]), followed by invasive device placement (10 [22.7%]) or arterial embolization (9 [20.5%]). Thirty‐eight (86.4%) patients were able to be adequately graded for hemostatic efficacy. Overall, 30 (78.9%) patients achieved excellent or good hemostasis within 24 h after periprocedural administration of andexanet alfa (19 [82.6%] apixaban vs. 11 [78.6%] rivaroxaban; 12 [80.0%] intracranial events vs. 18 [78.3%] extracranial events). Discharge disposition was most often to a short‐ or long‐term care facilities (27 [61.4%]). Thirty‐day mortality and thromboischemic complications occurred in 15 (34.1%) and 12 (27.3%) patients, respectively. Prothrombin time and antifactor Xa assay results were significantly decreased after andexanet alfa administration (p < 0.05) while thromboelastogram assay values (reaction time, kinetic time, and activated clotting time) showed nonsignificant changes pre‐ versus postreversal. Conclusion Andexanet alfa may be used for urgent or emergent reversal of apixaban and rivaroxaban peri‐procedurally with promising hemostatic outcomes. Further prospective, comparative clinical research is warranted.