氯吡格雷药物基因检测在支架辅助治疗颅内动脉瘤中的初步应用  

Clopidogrel pharmacogenomic testing preliminary application in stentassisted coiling treatment of intracranial aneurysms

作　　者：刘佳强[1] 李真保[1] 刘俊[2] 方兴根[1] 赵心同[1] 吴德刚[1] 陈三送[1] 方新运[1] 张家旗[1] 

机构地区：[1]皖南医学院附属弋矶山医院神经外科 [2]皖南医学院附属弋矶山医院药剂科

出　　处：《中国临床药理学与治疗学》2016年第3期313-317,346,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

摘　　要：目的：探讨氯吡格雷药物基因检测在支架辅助弹簧圈栓塞治疗颅内动脉瘤中应用的意义及前景。方法：选取我院行支架辅助弹簧圈栓塞术治疗颅内动脉瘤病人64例,行氯吡格雷药物基因检测,通过对CYP2C19~＊2、CYP2C19~＊3、CYP2C19~＊17和ABCB1-3435C四个基因位点的检测,分析其CYP2C19酶的代谢类型和ABCB1基因的表达类型。其中45例病人于住院期间行颅内动脉瘤支架辅助弹簧圈栓塞术,并行氯吡格雷药物基因检测,根据检测结果制定双抗用药方案;19例随访病人系颅内动脉瘤支架辅助治疗术后来院复查脑血管造影期间予行氯吡格雷药物基因检测,采用常规剂量双抗用药。结果：45例住院患者中20例患者基因型异常,常规剂量双抗用药血栓形成风险增加,均根据检测结果更改用药方案,4例患者出现有血栓类并发症表现;19例随访患者中共检测出3例基因型异常患者,其中2例患者曾出现有血栓栓塞并发症表现,通过积极溶栓治疗后症状消失,余患者在住院期间及随访中均未出现任何疑似血栓类并发症表现。结论：CYP2C19基因和ABCB1基因均有较高的人群变异率,基因变异发生氯吡格雷低反应性,影响支架术后双抗效果;氯吡格雷药物基因检测可作为支架辅助弹簧圈栓塞治疗颅内动脉瘤的一项常规检查,提供个体化的用药建议,对支架术后的双抗治疗具有指导意义。基因检测为导向的个体化治疗是今后发展的方向。AIM： To investigate the application value and to foresee the prospect of clopidogrel phar- macogenomic testing preliminary application in stent- assisted coiling treatment of intracranial aneurysms. METHODS： 64 patients with intracranial aneu- rysms treated with stent-assisted coiling embolization in our hospital were selected for clopidogrel pharma- cogenomic testing. Through the detection of four loci including CYP2C19＊ 2, CYP2C19＊ 3, CYP2C19 ＊17 and ABCB1-3435C, metabolic types of CYP2C19 enzyme and expression patterns of ABCB1 gene were analyzed. Among them, 45 patients underwent stent-assisted coiling embolization of intracranial an- eurysms and clopidogrel pharmacogenomic testing during hospitalization. Dual antiplatelet therapy pro- grams were developed based on test results; 19 fol-lowed-up patients with intracranial aneurysm under- went clopidogrel pharmacogenomic testing during re- examination of cerebral angiography after stent-assis- ted therapy, and conventional doses of dual anti- platelet drugs were used. RESULTS：In 45 hospi- talized patients, 20 had abnormal genotypes. The risk of thrombosis was increased using conventional doses of dual antiplatelet drugs, so therapy regimens were changed based on test results. And 4 patients had thrombotic complications; abnormal genotypes were detected in 3 of 19 followed-up patients, 2 pa- tients once presented thromboembolic complications, and symptoms disappeared after positive thrombolytic therapy, the remaining patients had no suspected thrombotic complications during hospitalization and follow-up visits. CONCLUSION ： Both CYP2C19 and ABCB1 genes have a higher population mutation rate. Genetic mutation induces clopidogrel low re- sponsiveness, impacting dual antiplatelet effects af- ter stent implantation; clopidogrel pharmacogenomic testing can be used as a routine examination for stent-assisted coiling embolization of intracranial an- eurysms to provide individualized treatment recom- mendations, which has a guiding significance for du- al

关 键 词：动脉瘤 支架 氯吡格雷 基因检测 双抗 

分 类 号：R969.1[医药卫生—药理学]