Full Study Report of Andexanet Alfa for Bleeding Associated with Factor Xa Inhibitors
Full Study Report of Andexanet Alfa for Bleeding Associated with Factor Xa Inhibitors
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DOI：
10.1056/nejmoa1814051
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发表时间：
2019-04-04
影响因子：
158.5
通讯作者：
Milling, T. J., Jr.
中科院分区：
文献类型：
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作者：
Connolly, S. J.;Crowther, M.;Milling, T. J., Jr.
Andexanet alfa是一种改良的重组人Xa因子的无活性形式，用于逆转Xa因子抑制剂。方法我们评估了352例在给予Xa因子抑制剂后18小时内发生急性大出血的患者。患者接受了一剂anddexanet，随后输液2小时。主要结果是andexanet治疗后抗Xa因子活性的变化百分比，以及输注结束后12小时止血效果优良或良好的患者百分比，止血效果根据预先规定的标准来判断。在确认大出血且基线抗Xa因子活性至少为75 ng / ml的患者亚组中评估疗效（对于接受依诺肝素治疗的患者，>= 0.25 IU / ml）。结果患者平均年龄77岁，多数有严重的心血管疾病。出血主要发生在颅内（227例[64%]）或胃肠道（90例[26%]）。在接受阿哌沙班治疗的患者中，抗Xa因子活性中位数从基线时的149.7 ng / ml降至阿德沙奈后的11.1 ng / ml（降低92%，95%可信区间[CI]， 91 - 93）；在接受利伐沙班治疗的患者中，中位值从211.8 ng / ml降至14.2 ng / ml（降低92%；95% CI, 88 - 94）。249例可评估的患者中有204例（82%）出现优秀或良好止血。在30天内，49例（14%）患者死亡，34例（10%）患者发生血栓形成事件。抗Xa因子活性降低总体上不能预测止血效果，但在颅内出血患者中有一定的预测作用。结论：在与使用Xa因子抑制剂相关的急性大出血患者中，anddexanet治疗可显著降低抗Xa因子活性，82%的患者在12小时内具有优异或良好的止血效果，根据预先规定的标准进行判定。（由Portola制药公司资助；附件a -4 ClinicalTrials.gov编号，.）
Background Andexanet alfa is a modified recombinant inactive form of human factor Xa developed for reversal of factor Xa inhibitors. Methods We evaluated 352 patients who had acute major bleeding within 18 hours after administration of a factor Xa inhibitor. The patients received a bolus of andexanet, followed by a 2-hour infusion. The coprimary outcomes were the percent change in anti-factor Xa activity after andexanet treatment and the percentage of patients with excellent or good hemostatic efficacy at 12 hours after the end of the infusion, with hemostatic efficacy adjudicated on the basis of prespecified criteria. Efficacy was assessed in the subgroup of patients with confirmed major bleeding and baseline anti-factor Xa activity of at least 75 ng per milliliter (or >= 0.25 IU per milliliter for those receiving enoxaparin). Results Patients had a mean age of 77 years, and most had substantial cardiovascular disease. Bleeding was predominantly intracranial (in 227 patients [64%]) or gastrointestinal (in 90 patients [26%]). In patients who had received apixaban, the median anti-factor Xa activity decreased from 149.7 ng per milliliter at baseline to 11.1 ng per milliliter after the andexanet bolus (92% reduction; 95% confidence interval [CI], 91 to 93); in patients who had received rivaroxaban, the median value decreased from 211.8 ng per milliliter to 14.2 ng per milliliter (92% reduction; 95% CI, 88 to 94). Excellent or good hemostasis occurred in 204 of 249 patients (82%) who could be evaluated. Within 30 days, death occurred in 49 patients (14%) and a thrombotic event in 34 (10%). Reduction in anti-factor Xa activity was not predictive of hemostatic efficacy overall but was modestly predictive in patients with intracranial hemorrhage. Conclusions In patients with acute major bleeding associated with the use of a factor Xa inhibitor, treatment with andexanet markedly reduced anti-factor Xa activity, and 82% of patients had excellent or good hemostatic efficacy at 12 hours, as adjudicated according to prespecified criteria. (Funded by Portola Pharmaceuticals; ANNEXA-4 ClinicalTrials.gov number, .)