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andexanet alfa治疗因子Ⅹa抑制剂相关出血的完整研究报告
Full Study Report of Andexanet Alfa for Bleeding Associated with Factor Xa Inhibitors


Stuart J. Connolly ... 心脑血管疾病 • 2019.04.04
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抗栓利器Xa因子抑制剂终于有了“开关”

 

陈奕奕,王伊龙*

首都医科大学附属北京天坛医院

*通讯作者

 

治疗血栓栓塞性疾病及预防房颤引起的卒中,目前主要使用华法林及包括凝血因子Xa抑制剂等的新型口服抗凝药(NOAC)。然而,Xa因子抑制剂因为没有相应的“红牌”药物(拮抗剂)而为广大临床医生所担心。2019年4月4日一期的《新英格兰医学杂志》(NEJM)发表了针对Xa因子抑制剂的“解毒剂” andexanet alfa的名为ANNEXA-4临床试验的最终结果(2019年2月7日在线发表)1

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摘要


背景

andexanet alfa是人凝血因子Ⅹa的重组改构非活性形式,开发用于逆转因子Ⅹa抑制剂的作用。

 

方法

我们评价了在给予因子Ⅹa抑制剂后18小时内发生急性大出血的352例患者。患者接受了andexanet推注,随后接受了2小时输入。共同主要结局为andexanet治疗后抗因子Ⅹa活性的变化百分比,以及在输入结束后12小时,止血效果根据预设标准被裁定为优秀或良好的患者百分比。本试验在被证实有大出血并且基线抗因子Ⅹa活性至少为75 ng/mL(对于接受依诺肝素治疗的患者为≥0.25 IU/mL)的患者亚组中评估了疗效。

 

结果

患者平均年龄为77岁,大多数患严重的心血管疾病。出血主要为颅内出血(227例患者[64%])或胃肠出血(90例患者[26%])。在接受阿哌沙班治疗的患者中,中位抗因子Ⅹa活性从基线时的149.7 ng/mL降低至andexanet推注后的11.1 ng/mL(降低92%;95%置信区间[CI],91%~93%);在接受利伐沙班治疗的患者中,中位值从211.8 ng/mL降低至14.2 ng/mL(降低92%;95% CI,88%~94%)。在可评价的249例患者中,204例(82%)达到了优秀或良好止血。在30日内,49例患者(14%)死亡,34例(10%)发生了血栓性事件。抗因子Ⅹa活性降低在总体患者中不能预测止血效果,但在颅内出血患者中能一定程度预测止血效果。

 

结论

在发生因子Ⅹa抑制剂相关急性大出血的患者中,andexanet治疗显著降低了抗因子Ⅹa活性,并且根据预设标准,82%的患者在12小时达到优秀或良好的止血效果(由Portola Pharmaceuticals资助;ANNEXA-4在ClinicalTrials.gov注册号为NCT02329327)。





作者信息

Stuart J. Connolly, M.D., Mark Crowther, M.D., John W. Eikelboom, M.D., C. Michael Gibson, M.D., John T. Curnutte, M.D., Ph.D., John H. Lawrence, M.D., Patrick Yue, M.D., Michele D. Bronson, Ph.D., Genmin Lu, Ph.D., Pamela B. Conley, Ph.D., Peter Verhamme, M.D., Ph.D., Jeannot Schmidt, M.D., Saskia Middeldorp, M.D., Alexander T. Cohen, M.D., Jan Beyer-Westendorf, M.D., Pierre Albaladejo, M.D., Jose Lopez-Sendon, M.D., Andrew M. Demchuk, M.D., Daniel J. Pallin, M.D., Mauricio Concha, M.D., Shelly Goodman, B.S.N., R.N., Janet Leeds, Ph.D., Sonia Souza, Ph.D., Deborah M. Siegal, M.D, Elena Zotova, Ph.D., Brandi Meeks, M.Sc., Sadia Ahmad, M.B., B.S., Juliet Nakamya, Ph.D., and Truman J. Milling, Jr., M.D. for the ANNEXA-4 Investigators*
From the Population Health Research Institute (S.J.C., J.W.E., D.M.S., E.Z., B.M., S.A., J.N.) and the Department of Medicine (M. Crowther), McMaster University, Hamilton, ON, and the University of Calgary, Calgary, AB (A.M.D.) — all in Canada; Harvard Medical School (C.M.G.) and Brigham and Women’s Hospital (D.J.P.) — both in Boston; Portola Pharmaceuticals, South San Francisco, CA (J.T.C., J.H.L., P.Y., M.D.B., G.L., P.B.C., S.G., J.L., S.S.); University of Leuven, Leuven, Belgium (P.V.); Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand (J.S.), and Grenoble-Alpes University Hospital, Grenoble (P.A.) — both in France; Academic Medical Center, Amsterdam (S.M.); Guy’s and St. Thomas’ Hospitals, King’s College London, London (A.T.C.); University Hospital Carl Gustav Carus Dresden, Dresden, Germany (J.B.-W.); Instituto de Investigación Hospital Universitario La Paz, Madrid (J.L.-S.); Sarasota Memorial Hospital, Sarasota, FL (M. Concha); and Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.). Address reprint requests to Dr. Connolly at the Population Health Research Institute, Hamilton Health Sciences, 237 Barton St. E, Hamilton, ON L8L 2X2, Canada, or at connostu@phri.ca. *A complete list of the ANNEXA-4 investigators is provided in the Supplementary Appendix, available at NEJM.org.

 

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