Department of Pharmacy, UC Health - University of Cincinnati Medical Center, Cincinnati, Ohio, USA.
University of Cincinnati James L. Winkle College of Pharmacy, Cincinnati, Ohio, USA.
Pharmacotherapy. 2022 Oct;42(10):780-791. doi: 10.1002/phar.2727. Epub 2022 Sep 23.
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.
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.
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.
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.
在需要紧急或急诊侵入性手术的患者中,使用andexanet alfa 逆转因子 Xa 抑制剂的结果尚缺乏。本研究旨在描述在侵入性手术 24 小时内使用 andexanet alfa 后的疗效和安全性结果。
这是一项单中心、观察性、回顾性研究,纳入了在侵入性或手术 24 小时内接受 andexanet alfa 治疗的患者。主要结局是使用类似于 ANNEXA-4 标准的类似定义,将止血效果评为优秀、良好或差。次要结局包括出院去向、重症监护病房(ICU)和住院时间、30 天死亡率、30 天血栓栓塞事件发生率以及逆转前后的血清凝血检测变化。
44 名患者符合纳入标准;其中,27 名(62.8%)接受了阿哌沙班治疗,16 名(37.2%)在入院前接受了利伐沙班治疗。逆转的适应症分为颅内(n=20 [45.5%])或颅外(n=24 [54.5%])部位。大多数患者需要紧急手术(18 [40.9%]),其次是侵入性器械放置(10 [22.7%])或动脉栓塞(9 [20.5%])。38 名(86.4%)患者能够充分评估止血效果。总体而言,30 名(78.9%)患者在围手术期使用 andexanet alfa 后 24 小时内达到良好或优秀的止血效果(19 名阿哌沙班 vs. 11 名利伐沙班;12 名颅内事件 vs. 18 名颅外事件)。出院去向最常为短期或长期护理机构(27 [61.4%])。30 天死亡率和血栓栓塞并发症分别发生在 15 名(34.1%)和 12 名(27.3%)患者中。使用 andexanet alfa 后,凝血酶原时间和抗因子 Xa 检测结果显著降低(p<0.05),而血栓弹性图检测值(反应时间、动力学时间和激活凝血时间)在逆转前后无显著变化。
andexanet alfa 可用于紧急或急诊手术时,在围手术期迅速逆转阿哌沙班和利伐沙班的抗凝作用,具有良好的止血效果。需要进一步开展前瞻性、对照临床研究。