依达赛珠单抗在中国人群对达比加群酯抗凝作用的逆转效应  

Reversal effect of idarucizumab on the anticoagulant effect of dabigatran etexilate in Chinese population

作　　者：杨艳敏 马长生[2] 周菁[3] 刘少稳[4] 王利宏[5] 王建安[6] 吴书林[7] 王景峰[8] 汤宝鹏[9] 洪葵[10] 周浩[11] 朱文静 李文芳 张澍 Yang Yanmin;Ma Changsheng;Zhou Jing;Liu Shaowen;Wang Lihong;Wang Jianan;Wu Shulin;Wang Jingfeng;Tang Baopeng;Hong Kui;Zhou Hao;Zhu Wenjing;Li Wenfang;Zhang Shu(Emergency and Intensive Care Center,Fuwai Hospital,State Key Laboratory of Cardiovascular Disease,National Center for Cardiovascular Diseases,Chinese Academy of Medical Sciences,Peking Union Medical College,Beijing 100037,China;Department of Cardiology,Capital Medical University Affiliated Beijing Anzhen Hospital,Beijing 100020,China;Department of Cardiology,Peking University First Hospital,Beijing 100034,China;Department of Cardiology,Shanghai Central Hospital,Shanghai 200940,China;Department of Cardiology,Zhejiang Provincial People's Hospital,Hangzhou 310014,China;Department of Cardiology,The Second Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou 310003,China;Department of Cardiology,Guangdong General Hospital,Guangzhou 510080,China;Department of Cardiology,The Sun Yat-sen Memorial Hospital of Sun Yat-sen University,Guangzhou 510120,China;Department of Pacing and Electrophysiology,Department of Cardiac Electrophysiology and Remodeling,The First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,China;Department of Cardiology,The Second Affiliated Hospital of Nanchang University,Nanchang 330008,China;Department of Cardiology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325015,China;Boehringer Ingelheim Investment Co.,Ltd.Shanghai 200040,China;Center of Arrhythmia,Fuwai Hospital,State Key Laboratory of Cardiovascular Disease,National Center for Cardiovascular Diseases,Chinese Academy of Medical Sciences,Peking Union Medical College,Beijing 100037,China)

机构地区：[1]中国医学科学院、北京协和医学院、国家心血管病中心、心血管疾病国家重点实验室、阜外医院急重症中心,北京100037 [2]首都医科大学附属北京安贞医院心内科,北京100020 [3]北京大学第一医院心内科,北京100034 [4]上海市第一人民医院心内科,上海200940 [5]浙江省人民医院心内科,杭州310014 [6]浙江大学医学院附属第二医院心脏中心,杭州310003 [7]广东省人民医院心内科,广州510080 [8]中山大学孙逸仙纪念医院心内科,广州510120 [9]新疆医科大学第一附属医院心脏中心起搏电生理科新疆心电生理与心脏重塑重点实验室,乌鲁木齐830054 [10]南昌大学第二附属医院心内科心血管病研究所,南昌330008 [11]温州医科大学附属第一医院心内科,温州325015 [12]勃林格殷格翰(中国)投资有限公司,上海200040 [13]中国医学科学院、北京协和医学院、国家心血管病中心、心血管疾病国家重点实验室、阜外医院心律失常中心,北京100037

出　　处：《中华心律失常学杂志》2022年第6期553-560,共8页Chinese Journal of Cardiac Arrhythmias

摘　　要：目的评价依达赛珠单抗在中国人群对达比加群酯抗凝作用的逆转效应。方法本文为开放标签多中心研究。收集2018年10月至2020年7月全国11个中心因无法控制出血、需紧急手术或其他有创操作需要使用依达赛珠单抗逆转达比加群酯抗凝作用的患者。分为两组:大出血组(A组)为发生无法控制、危及生命的出血者;非大出血组(B组)为需要急诊外科手术或其他有创操作者。两组患者均接受静脉输注依达赛珠单抗5 g。主要终点为患者首次输注依达赛珠单抗结束至最后1次输注完成后4 h内稀释凝血酶时间和蝰蛇毒凝血时间最大逆转效应。同时记录首次输注至第2次输注完成后5 d内不良事件的发生情况。结果研究纳入19例患者,其中男10例,女9例,年龄(71.4±13.0)岁,年龄范围48~93岁。A组13例,B组6例。4 h内达比加群酯抗凝效应最大逆转的中位值均为100%。治疗期内,17例(89.5%,17/19)患者出现不良事件。其中重点报道不良事件9例,包括2例(10.5%,2/19)血栓栓塞事件、4例(21.1%,4/19)严重不良事件,经研究者判断,严重不良事件及血栓栓塞事件均与依达赛珠单抗无关;3例(15.8%,3/19)出现研究者定义的药物相关的不良事件。治疗期内患者无死亡。研究中抗依达赛珠抗体结果均为阴性,并与免疫原性无关。结论给予依达赛珠单抗5 g后最初4 h内达比加群酯抗凝作用的中位最大逆转效应达100%,且安全性好对临床实践有借鉴价值。Objective To evaluate the reversal of the anticoagulation effect of dabigatran with idarucizumab in Chinese patients.Methods From October 2018 to July 2020,19 patients in 11 centers across the country who needed to use idarucizumab to reverse the anticoagulation effect of dabigatran etexilate due to uncontrolled bleeding,emergency surgery or other invasive procedures were enrolled.The patients who treated with dabigatran etexilatewere included due to that they had uncontrolled/life-threatening bleeding requiring urgent medical or surgical intervention(group A);or patients who might not have been bleeding,but required an emergency surgery or other invasive procedure for a condition other than bleeding(group B).Both groups received an intravenous infusion of 5 g idarucizumab.The primary endpoint was the maximum reversal of the anticoagulation effect of dabigatran based on the diluted thrombin time(dTT)and ecarin clotting time(ECT)evaluated at the central laboratory,from the end of the first infusion up to 4 hours after the last infusion.Safety during the treatment period was assessed between the first infusion and 5 days after the last infusion.Meanwhile,the adverse events occurred from the first infusion to the 5 days afterthe second infusion were recorded.Results Eleven sites recruited a total of 19 patients(group A:13 patients;group B:6 patients).There were 10 males and 9 females,aged(71.4±13.0)years old,ranging from 48 to 93 years old.The median maximum reversal of the anticoagulation effect of dabigatran from the end of the first infusion up to 4 hours after the last infusion was both 100%.During the treatment period,any adverse events(AE)occurred in 17 patients(89.5%,17/19).Key AE include 2 patients reported thrombotic events(10.5%,2/19),and serious AE occurred in 4 patients(21.1%,4/19);these events were considered not related to idarucizumab by the investigators.Investigator defined drug-related AE occurred in 3 patients(15.8%,3/19).No death was reported during the treatment period.Anti-drug antibody result

关 键 词：抗凝药 依达赛珠单抗 达比加群酯 逆转剂 出血 紧急手术 

分 类 号：R969.3[医药卫生—药理学]