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Association Between ABCB1 Polymorphisms and Outcomes of Clopidogrel Treatment in Patients With Minor Stroke or Transient Ischemic Attack Secondary Analysis of a Randomized Clinical Trial

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收录情况： ◇ SCIE ◇ CPCI(ISTP)

作者：
Pan, Yuesong[1,2,3,4] * ; Chen, Weiqi[1,2,3,4] ; Wang, Yilong[1,2,3,4,12] ; Li, Hao[1,2,3,4] ; Johnston, S. Claiborne[5,13] ; Simon, Tabassome[6,7,8,9] ; Zhao, Xingquan[1,2,3,4,12] ; Liu, Liping[1,2,3,4] ; Wang, David[10,11] ; Meng, Xia[1,2,3,4] ; Wang, Yongjun[1,2,3,4,12,*1] ; Wang, Yongjun[1,2,3,4,12,*1] ; Wang, Yilong[1,2,3,4,12] ; Zhao, Xingquan[1,2,3,4,12] ; Johnston, S. Claiborne[5,13] ; Wang, Zhimin[14] ; Xia, Haiqin[15] ; Zhang, Guiru[16] ; Ren, Xudong[17] ; Ji, Chunling[18] ; Zhang, Guohua[19] ; Li, Jianhua[1,2,3,4,20] ; Lu, Bohua[21] ; Wang, Liping[22] ; Feng, Shutao[23] ; Wang, Dali[10,11,24] ; Tang, Weiguo[25] ; Li, Juntao[1,2,3,4,26] ; Zhang, Hongtian[27] ; Li, Guanglai[1,2,3,4,28] ; Wang, Baojun[29] ; Chen, Yuhua[1,2,3,4,30] ; Lian, Ying[31] ; Liu, Bin[1,2,3,4,32] ; Teng, Junfang[33] ; Sui, Rubo[34] ; Li, Lejun[1,2,3,4,35] ; Yuan, Zhiling[36] ; Zang, Dawei[37] ; Lu, Zuneng[38] ; Sun, Li[39] ; Wang, Dong[10,11,40] ; Hou, Liying[41] ; Yuan, Dongcai[42] ; Cao, Yongliang[43] ; Li, Hui[1,2,3,4,44] ; Tan, Xiuge[45] ; Wang, Huicong[46] ; Du, Haisong[47] ; Liu, Mingyi[1,2,3,4,48] ; Wang, Suping[49] ; Liu, Qiuwu[1,2,3,4,50] ; Zhang, Zhong[51] ; Cui, Qifu[52] ; Wang, Runqing[53] ; Zhao, Jialin[1,2,3,4,54] ; Zhang, Jiewen[55] ; Zhao, Jianping[1,2,3,4,56] ; Bi, Qi[57] ; Qi, Xiyou[58] ; Liu, Junyan[1,2,3,4,59] ; Li, Changxin[1,2,3,4,60] ; Li, Ling[1,2,3,4,61] ; Pan, Xiaoping[1,2,3,4,62] ; Zhang, Junling[63] ; Jiao, Derang[64] ; Han, Zhao[65] ; Qian, Dawei[66] ; Xiao, Jin[67] ; Xing, Yan[68] ; Du, Huishan[69] ; Huang, Guang[70] ; Cui, Yongqiang[71] ; Li, Yan[1,2,3,4,72] ; Feng, Lianyuan[73] ; Gao, Lianbo[74] ; Xiao, Bo[75] ; Cao, Yibin[76] ; Wu, Yiping[77] ; He, Maolin[91] ; Liu, Jinfeng[1,2,3,4,78] ; Zhang, Zhiming[79] ; Dong, Zhengxie[80] ; Wang, Limin[81] ; He, Li[82] ; Wang, Xinchen[83] ; Guo, Xueying[84] ; Wang, Ming[85] ; Wang, Xiaosha[86] ; Jiang, Jiandong[87] ; Zhao, Renliang[1,2,3,4,88] ; Zhou, Shengnian[89] ; Hu, Hao[90] ; Yu, Fengchun[92] ; Ouyang, Quping[93] ; Zhang, Jingbo[94] ; Xu, Anding[95] ; Qi, Xiaokun[96] ; Wang, Lei[97] ; Shi, Fuming[98] ; Guo, Fuqiang[99] ; Wang, Jianfeng[100] ; Zhao, Fengli[1,2,3,4,101] ; Dou, Ronghua[102] ; Wei, Dongning[103] ; Meng, Qingwei[1,2,3,4,104] ; Xia, Yilu[105] ; Wang, Shimin[106] ; Xue, Zhangcang[107] ; Xu, Yuming[33] ; Ma, Liping[108] ; Wang, Chun[109] ; Wu, Jiang[110] ; Du, Yifeng[111] ; Wang, Yinzhou[1,2,3,4,112] ; Xiao, Lijun[113] ; Song, Fucong[114] ; Hu, Wenli[115] ; Chen, Zhigang[1,2,3,4,116] ; Liu, Qingrui[1,2,3,4,117] ; Zhang, Jiemin[118] ; Chen, Mei[1,2,3,4,119] ; Yuan, Xiaodong[120] ; Liu, Zhihui[1,2,3,4,121] ; Li, Guozhong[1,2,3,4,122] ; Li, Xiaohong[1,2,3,4,123] ; Tian, Tingchen[124] ;
单位： [1]Capital Med Univ, Beijing Tiantan Hosp, Dept Neurol, Beijing, Peoples R China [2]China Natl Clin Res Ctr Neurol Dis, Beijing, Peoples R China [3]Beijing Inst Brain Disorders, Ctr Stroke, Beijing, Peoples R China [4]Beijing Key Lab Translat Med Cerebrovasc Dis, Beijing, Peoples R China [5]Univ Texas Austin, Dell Med Sch, Deans Off, Austin, TX 78712 USA [6]AP HP, Dept Clin Pharmacol, Paris, France [7]AP HP, Clin Res Platform East Paris, URCEST, CRC,CRB, Paris, France [8]Sorbonne Univ, Dept Clin Pharmacol, Paris, France [9]FACT, Paris, France [10]OSF Healthcare Syst, Illinois Neurol Inst Stroke Network, Peoria, IL USA [11]Univ Illinois, Coll Med Peoria, Dept Neurol, Peoria, IL USA [12]Beijing Tiantan Hosp, Beijing, Peoples R China [13]Univ Texas Austin, Dell Med Sch, Austin, TX 78712 USA [14]Taizhou First Peoples Hosp, Taizhou, Peoples R China [15]Taiyuan Iron & Steel Grp Co Ltd, Gen Hosp, Taiyuan, Shanxi, Peoples R China [16]Penglai Peoples Hosp, Yantai, Peoples R China [17]Third Peoples Hosp Datong, Datong, Peoples R China [18]Fourth Cent Hosp Tianjin, Tianjin, Peoples R China [19]Hebei Med Univ, Hosp 2, Shijiazhuang, Hebei, Peoples R China [20]First Hosp Fangshan Dist, Beijing, Peoples R China [21]Beijing Puren Hosp, Beijing, Peoples R China [22]Tianjin Ninghe Dist Hosp, Tianjin, Peoples R China [23]Peoples Hosp Zhengzhou, Zhengzhou, Henan, Peoples R China [24]North China Coal Med Coll, Affiliated Hosp, Tangshan, Peoples R China [25]Zhejiang Zhoushan Hosp, Zhoushan, Peoples R China [26]HanDan Cent Hosp, Handan, Peoples R China [27]Zhecheng Peoples Hosp, Zhecheng, Peoples R China [28]Shanxi Med Univ, Hosp 2, Taiyuan, Shanxi, Peoples R China [29]Baotou Cent Hosp, Baotou, Peoples R China [30]Gen Hosp Changjiang River Shipping, Wuhan, Hubei, Peoples R China [31]Dalian Econ & Technol Dev Zone Hosp, Dalian, Peoples R China [32]North China Coal Med Coll, Affiliated Hosp, Neurol Dept 1, Tangshan, Peoples R China [33]Zhengzhou Univ, Affiliated Hosp 1, Zhengzhou, Henan, Peoples R China [34]Liaoning Med Univ, Affiliated Hosp 1, Jinzhou, Peoples R China [35]Lianyungang Municipal Hosp TCM, Lianyungang, Peoples R China [36]Cent Hosp Qiu Cty, Handan, Peoples R China [37]Tianjin First Ctr Hosp, Tianjin, Peoples R China [38]Wuhan Univ, Renmin Hosp, Wuhan, Hubei, Peoples R China [39]Qingdao Cent Hosp, Qingdao, Shandong, Peoples R China [40]Baogang Hosp, Baotou, Peoples R China [41]Changzhi City Peoples Hosp Shanxi Prov, Changzhi, Peoples R China [42]Harrison Int Peace Hosp, Hengshui, Peoples R China [43]Peoples Hosp Linzi Dist, Zibo, Peoples R China [44]Yantai Mt Hosp, Yantai, Peoples R China [45]Beijing Pinggu Dist Hosp, Beijing, Peoples R China [46]Taiyuan Cent Hosp, Taiyuan, Shanxi, Peoples R China [47]Chengde Cent Hosp, Chengde, Peoples R China [48]Shijiazhuang Cent Hosp, Shijiazhuang, Hebei, Peoples R China [49]Dalian Municipal Cent Hosp, Neurol Dept 1, Dalian, Peoples R China [50]Xian 141 Hosp, Xian, Shaanxi, Peoples R China [51]Chengdu Third Municipal Peoples Hosp, Chengdu, Sichuan, Peoples R China [52]Chifeng Univ, Affiliated Hosp, Chifeng, Peoples R China [53]Zhengzhou Cent Hosp, Zhengzhou, Henan, Peoples R China [54]Lihuili Hosp, Med Ctr, Ningbo, Zhejiang, Peoples R China [55]Henan Prov Peoples Hosp, Zhengzhou, Henan, Peoples R China [56]Jinzhong City Second Hosp, Jinzhong, Peoples R China [57]Capital Med Univ, Beijing Anzhen Hosp, Beijing, Peoples R China [58]Beijing Huairou Dist Chinese Med Hosp, Beijing, Peoples R China [59]Hebei Med Univ, Hosp 3, Shijiazhuang, Hebei, Peoples R China [60]Shanxi Med Univ, Affiliated Hosp 1, Taiyuan, Shanxi, Peoples R China [61]Hebei Prov Peoples Hosp, Shijiazhuang, Hebei, Peoples R China [62]Guangzhou First Municipal Peoples Hosp, Guangzhou, Guangdong, Peoples R China [63]Cent Hosp Cangzhou, Cangzhou, Peoples R China [64]Chinese Peoples Armed Police Force Med Sch, Affiliated Hosp, Tianjin, Peoples R China [65]ZhejiangWenzhou Med Coll, Affiliated Hosp 1, Wenzhou, Peoples R China [66]Jilin Cent Hosp, Jilin, Jilin, Peoples R China [67]Anhui Maanshan Cent Hosp, Maanshan, Peoples R China [68]Beijing Aviat Ind Cent Hosp, Beijing, Peoples R China [69]Luhe Hosp, Beijing, Peoples R China [70]Capital Med Univ, Beijing Fuxing Hosp, Beijing, Peoples R China [71]306th Hosp PLA, Beijing, Peoples R China [72]Tianjin Univ Chinese Med, Affiliated Hosp 1, Tianjin, Peoples R China [73]Baiqiuen Int Peace Hosp Peoples Liberat Army, Shijiazhuang, Hebei, Peoples R China [74]China Med Univ, Affiliated Hosp 4, Shenyang, Liaoning, Peoples R China [75]Cent S Univ, Xiangya Hosp, Xiangya, Peoples R China [76]TangshanWorkers Hosp, Tangshan, Peoples R China [77]1st Hosp Handan, Handan, Peoples R China [78]Yangquan Coal Grp Co Ltd, Gen Hosp, Yangquan, Peoples R China [79]Tianjin Tianhe Hosp, Tianjin, Peoples R China [80]Nantong First Peoples Hosp, Nantong, Peoples R China [81]1st Hosp Zhangjiakou City, Zhangjiakou, Peoples R China [82]West China Hosp, Chengdu, Sichuan, Peoples R China [83]Shandong Univ TCM, Affiliated Hosp 2, Jinan, Shandong, Peoples R China [84]Fenyang Hosp Shanxi Prov, Fenyang, Peoples R China [85]Zhejiang Zhoushan Putuo Dist Peoples Hosp, Zhoushan, Peoples R China [86]China Acad Chinese Tradit Med, Xiyuan Hosp, Beijing, Peoples R China [87]2 Peoples Hosp East Lianyungang City, Lianyungang, Peoples R China [88]Qingdao Univ, Med Coll, Affiliated Hosp, Qingdao, Shandong, Peoples R China [89]Shandong Univ, Qilu Hosp, Jinan, Shandong, Peoples R China [90]Zibo Hosp Tradit Chinese Med, Zibo, Peoples R China [91]Beijing Shijitan Hosp, Beijing, Peoples R China [92]Beijing Haidian Hosp, Beijing, Peoples R China [93]Beijing Shunyi Dist Hosp, Beijing, Peoples R China [94]Dalian Third Municipal Hosp, Dalian, Peoples R China [95]Jinan Univ, Affliated Hosp 1, Guangzhou, Guangdong, Peoples R China [96]Navy Genaral Hosp PLA, Beijing, Peoples R China [97]Beijing Second Artillery Gen Hosp, Beijing, Peoples R China [98]Beijing Daxing Dist Hosp, Beijing, Peoples R China [99]Sichuan Prov Peoples Hosp, Chengdu, Sichuan, Peoples R China [100]Dalian Municipal Cent Hosp, Dalian, Peoples R China [101]Second Hosp Baoding, Baoding, Peoples R China [102]Hosp Combine Tradit Chinese & Western Med Cangzho, Cangzhou, Peoples R China [103]309th Hosp PLA, Beijing, Peoples R China [104]Liangxiang Hosp Fangshan Dist, Beijing, Peoples R China [105]Tsinghua Univ, HuaXin Hosp, Hosp 1, Beijing, Peoples R China [106]Tianjin Huanhu Hosp, Tianjin, Peoples R China [107]Shijiazhuang First Hosp, Shijiazhuang, Hebei, Peoples R China [108]Xinzhou City Peoples Hosp, Xinzhou, Peoples R China [109]Sichuan Prov Peoples Hosp Deyang City, Deyang, Peoples R China [110]Jilin Univ, Hosp 1, Jilin, Jilin, Peoples R China [111]Shandong Prov Hosp, Jinan, Shandong, Peoples R China [112]Fujian Prov Hosp, Fuzhou, Fujian, Peoples R China [113]Liaoyang City Third Peoples Hosp, Liaoyang, Peoples R China [114]Handan City Ctr Hosp, Handan, Peoples R China [115]Capital Med Univ, Beijing Chaoyang Hosp, Beijing, Peoples R China [116]Beijing Univ, Chinese Med East Hosp, Beijing, Peoples R China [117]Hebei Med Univ, Hosp 4, Shijiazhuang, Hebei, Peoples R China [118]Soochow Univ, Affiliated Hosp 4, Suzhou, Peoples R China [119]Zhejiang Univ, Chinese Med Affiliated Hosp 1, Hangzhou, Zhejiang, Peoples R China [120]Kailuan Co Ltd, Affiliated Hosp, Tangshan, Peoples R China [121]Weifang Med Univ, Affiliated Hosp, Weifang, Peoples R China [122]Harbin Med Univ, Hosp 1, Harbin, Heilongjiang, Peoples R China [123]Dalian Friendship Hosp, Dalian, Peoples R China [124]Tianjin Dagang Hosp, Tianjin, Peoples R China
出处：
DOI： 10.1001/jamaneurol.2018.4775
ISSN：

摘要：
IMPORTANCE Genetic variants of ABCB1 may affect intestinal absorption of clopidogrel bisulfate. However, it is unclear whether ABCB1 polymorphisms are associated with clopidogrel efficacy for minor ischemic stroke or transient ischemic attack (TIA). OBJECTIVES To investigate the association between ABCB1 polymorphisms and clopidogrel efficacy for minor stroke or TIA. DESIGN, SETTING, AND PARTICIPANTS In this prespecified secondary analysis of the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) randomized clinical trial, 3010 patients with minor stroke or TIA at 73 sites in China with experience in conducting genetic studies were included from October 1, 2009, to July 30, 2012. The analysis was conducted on March 20, 2018. Four single-nucleotide polymorphisms (ABCB1-154T>C [rs4148727], ABCB13435C>T [rs1045642], CYP2C19*2 [681G>A, rs4244285], and CYP2C19*3 [636G>A, rs4986893]) were genotyped among 2836 patients treated with clopidogrel plus aspirin (n = 1414) or aspirin alone (n = 1422). The association of ABCB1 genetic variants (-154 TC/CC and 3435 CT/TT) with clopidogrel efficacy was evaluated in the context of CYP2C19 status, another gene associated with clopidogrel efficacy. INTERVENTIONS Patients in the CHANCE trial were randomized to treatment with clopidogrel combined with aspirin or to aspirin alone. MAIN OUTCOMES AND MEASURES Primary efficacy outcome was stroke recurrence after 3 months. The safety outcome was any bleeding risk after 3 months. RESULTS Among 2836 patients, the median age was 61.8 years (interquartile range, 54.4-71.1 years) and 1887 patients (66.5%) were male. A total of 2146 (75.7%) patients were carriers of ABCB1-154TC/CC (570 [20.1%]) or 3435 CT/TT (1851 [65.3%]) genotype. Clopidogrel plus aspirin treatment was associated with reduced risk of new stroke in patients with ABCB1-154 TT and 3435 CC genotype (hazard ratio [HR], 0.43; 95% Cl, 0.26-0.71) but not in those with ABCB1 -154 TC/CC or 3435 CT/TT genotype (HR, 0.78; 95% CI, 0.60-1.03) compared with aspirin (P=.04 for interaction). A combined association of ABCB1 and CYP2C19 polymorphisms with new stroke was observed. The risk of bleeding for clopidogrel plus aspirin treatment was not associated with the ABCB1 genotypes (2.3% and 1.3% vs 1.9% and 2.2%; P=.25 for interaction in patients with or without ABCB1-154 TC/CC or 3435 CT/TT genotype) CONCLUSIONS AND RELEVANCE The ABCB1 polymorphism was associated with the reduced efficacy of clopidogrel plus aspirin treatment compared with aspirin among patients with minor ischemic stroke or TIA. Genetic polymorphism of ABCB1 should be considered when prescribing clopidogrel for these patients.

基金：
Ministry of Science and Technology of the People's Republic of ChinaMinistry of Science and Technology, China [2016YFC0901001, 2016YFC0901002, 2017YFC1310901, 2018YFC1311700, 2018YFC1311706]; Beijing Municipal Commission of Health and Family Planning [2016-1-2041, SML20150502]
语种：
外文
被引次数：
WOS：
中科院(CAS)分区：
出版当年[2018]版：
大类 | 1 区 医学
小类 | 1 区 临床神经病学
最新[2025]版：
大类 | 1 区 医学
小类 | 1 区 临床神经病学
JCR分区：
出版当年[2017]版：
Q1 CLINICAL NEUROLOGY
最新[2023]版：
Q1 CLINICAL NEUROLOGY

影响因子： 最新[2023版] 最新五年平均[2021-2025] 出版当年[2017版] 出版当年五年平均[2013-2017] 出版前一年[2016版] 出版后一年[2018版]

第一作者：
第一作者单位： [1]Capital Med Univ, Beijing Tiantan Hosp, Dept Neurol, Beijing, Peoples R China [2]China Natl Clin Res Ctr Neurol Dis, Beijing, Peoples R China [3]Beijing Inst Brain Disorders, Ctr Stroke, Beijing, Peoples R China [4]Beijing Key Lab Translat Med Cerebrovasc Dis, Beijing, Peoples R China
通讯作者：
通讯机构： [1]Capital Med Univ, Beijing Tiantan Hosp, Dept Neurol, Beijing, Peoples R China [2]China Natl Clin Res Ctr Neurol Dis, Beijing, Peoples R China [3]Beijing Inst Brain Disorders, Ctr Stroke, Beijing, Peoples R China [4]Beijing Key Lab Translat Med Cerebrovasc Dis, Beijing, Peoples R China [12]Beijing Tiantan Hosp, Beijing, Peoples R China [*1]119,South 4th Ring West Rd, Beijing 100070, Peoples R China
推荐引用方式(GB/T 7714)：
Pan Yuesong,Chen Weiqi,Wang Yilong,et al.Association Between ABCB1 Polymorphisms and Outcomes of Clopidogrel Treatment in Patients With Minor Stroke or Transient Ischemic Attack Secondary Analysis of a Randomized Clinical Trial[J].JAMA NEUROLOGY.2019,76(5):552-560.doi:10.1001/jamaneurol.2018.4775.
APA：
Pan, Yuesong,Chen, Weiqi,Wang, Yilong,Li, Hao,Johnston, S. Claiborne...&Tian, Tingchen.(2019).Association Between ABCB1 Polymorphisms and Outcomes of Clopidogrel Treatment in Patients With Minor Stroke or Transient Ischemic Attack Secondary Analysis of a Randomized Clinical Trial.JAMA NEUROLOGY,76,(5)
MLA：
Pan, Yuesong,et al."Association Between ABCB1 Polymorphisms and Outcomes of Clopidogrel Treatment in Patients With Minor Stroke or Transient Ischemic Attack Secondary Analysis of a Randomized Clinical Trial".JAMA NEUROLOGY 76..5(2019):552-560

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