Influence of CYP2C19 genetic polymorphisms on clinical outcomes of intracranial aneurysms treated with stent-assisted coiling
Influence of CYP2C19 genetic polymorphisms on clinical outcomes of intracranial aneurysms treated with stent-assisted coiling
复制标题
CYP2C19基因多态性对支架辅助弹簧圈治疗颅内动脉瘤临床结局的影响
DOI：
10.1136/neurintsurg-2016-012635
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发表时间：
2017-10-01
影响因子：
4.8
通讯作者：
Li, Youxiang
中科院分区：
文献类型：
--
作者：
Ge, Huijian;Lv, Xianli;Li, Youxiang
目的探讨CYP 2C 19基因多态性对支架辅助弹簧圈栓塞治疗颅内动脉瘤临床疗效的影响。方法2014年9月至2015年10月，我们前瞻性招募了215例接受支架辅助弹簧圈栓塞术治疗的颅内动脉瘤患者。测定CYP 2C 19基因型并检测氯吡格雷反应。主要终点包括症状性或无症状性缺血事件和出血事件。次要终点是3个月时的临床结局。 结果215例患者中，中代谢型（IMs，CYP 2C 19 *1/*2，*1/*3）108例（50.2%），强代谢型（EMs，CYP 2C 19 *1/*1）76例（35.3%），弱代谢型（PMs，CYP 2C 19 *2/*2，*2/*3，*3/*3）31例（14.4%）。CYP 2C 19功能丧失（LOF）等位基因（*2或 *3，p=0.001）携带者，尤其是PM（p=0.004），发生氯吡格雷抵抗的风险增加。术后，69例患者（32.1%）发生脑缺血事件，20例患者（9.3%）发生出血。与IM和PM相比，EM的缺血事件风险较低（分别为21.1% vs 37.0%和41.9%，p=0.02和0.027），出血事件风险相对较高（分别为18.4% vs 5.6%和0%，p=0.006和0.01）。基于多变量分析，CYP 2C 19 LOF等位基因携带（p=0.032）和氯吡格雷抵抗（p=0.047）被认为是脑缺血事件的预测因子，EM与出血显著相关（p=0.002）。后循环动脉瘤（p=0.038）、出血史（p=0.001）和不良代谢基因型（p=0.001）可能导致不良临床结局（改良兰金量表>2）。结论CYP 2C 19基因多态性对氯吡格雷的抗血小板作用有显著影响，可作为颅内动脉瘤支架辅助弹簧圈栓塞术患者缺血或出血事件甚至临床结局的危险因素。
Objective To investigate the influence of CYP2C19 genetic polymorphisms on clinical outcomes of intracranial aneurysms treated with stent-assisted coiling. Methods Between September 2014 and October 2015, we prospectively recruited 215 patients with intracranial aneurysms who were treated with stent-assisted coiling. CYP2C19 genotypes were determined and clopidogrel response was tested. The primary endpoints included symptomatic or silent ischemic events, and bleeding events. The secondary endpoint was clinical outcome at 3 months. Results Of the 215 patients, 108 (50.2%) were classified as intermediate metabolizers (IMs, CYP2C19*1/*2, *1/*3), 76 (35.3%) as extensive metabolizers (EMs, CYP2C19*1/*1) and 31 (14.4%) as poor metabolizers (PMs, CYP2C19*2/*2, *2/*3, *3/*3). Carriers of CYP2C19 loss-of-function (LOF) alleles (*2 or *3, p=0.001), especially PMs (p=0.004), had an increased risk for clopidogrel resistance. After the procedures, cerebral ischemic events occurred in 69 patients (32.1%) and bleeding was seen in 20 patients (9.3%). In comparison with IMs and PMs, EMs had a lower risk for ischemic events (21.1% vs 37.0% and 41.9%, p=0.02 and 0.027, respectively) and a relatively higher risk for bleeding events (18.4% vs 5.6% and 0%, p=0.006 and 0.01, respectively). Based on multivariate analysis, the carriage of CYP2C19 LOF alleles (p=0.032) and clopidogrel resistance (p=0.047) were considered as predictors of cerebral ischemic events, and EMs were significantly associated with bleeding (p=0.002). Posterior circulation aneurysms (p=0.038), hemorrhagic history (p=0.001) and poor metabolic genotypes (p=0.001) could result in poor clinical outcomes (modified Rankin Scale >2). Conclusions CYP2C19 genetic polymorphisms had significant influence on the antiplatelet effect of clopidogrel, and could be considered as risk factors of ischemic or bleeding events and even clinical outcomes of patients with intracranial aneurysms treated with stent-assisted coiling.