Division of Molecular & Clinical Medicine, School of Medicine, University of Dundee, Dundee, UK.
Medicines Monitoring Unit, School of Medicine, University of Dundee, Dundee, UK.
Clin Pharmacol Ther. 2018 Feb;103(2):281-286. doi: 10.1002/cpt.780. Epub 2017 Sep 19.
Clopidogrel efficacy is influenced by genetic variation of cytochrome P450 (CYP)2C19, however, few studies have considered patients who have a stroke. We used electronic medical records (EMRs) linked to a bioresource to examine real-world implications of clopidogrel pharmacogenetics in stroke. Patients hospitalized for any arterial thrombo-occlusive (ATO) event who subsequently redeemed clopidogrel prescriptions in the community were entered into the study (n = 651). During 24-month follow-up, the primary endpoint of recurrent ATO or death occurred in 299 patients (46%). CYP2C192 loss-of-function allele carriers had an increased risk (hazard ratio (HR) = 1.29; 95% confidence interval (CI) = 1.04-1.59; P = 0.019). In the ischemic stroke subgroup (n = 94), the estimate of risk was greater (HR = 2.23; 95% CI = 1.17-4.24; P = 0.015), which was further supported by a meta-analysis of available studies. In conclusion, we have demonstrated the clinical impact of CYP2C192 on clopidogrel efficacy using a purely EMR approach. This suggests that the risk in the ischemic stroke population may be particularly high.
氯吡格雷的疗效受细胞色素 P450（CYP）2C19 基因变异的影响，但很少有研究考虑过中风患者。我们使用与生物资源相关的电子病历（EMR）来研究氯吡格雷药物遗传学在中风中的实际意义。因任何动脉血栓闭塞（ATO）事件住院，随后在社区中使用氯吡格雷处方的患者被纳入研究（n=651）。在 24 个月的随访期间，299 名患者（46%）发生了复发性 ATO 或死亡的主要终点事件。CYP2C192 失活等位基因携带者的风险增加（风险比（HR）=1.29；95%置信区间（CI）=1.04-1.59；P=0.019）。在缺血性中风亚组（n=94）中，风险估计值更高（HR=2.23；95%CI=1.17-4.24；P=0.015），这一结果得到了对现有研究进行的荟萃分析的支持。总之，我们使用纯粹的 EMR 方法证明了 CYP2C192 对氯吡格雷疗效的临床影响。这表明在缺血性中风人群中的风险可能特别高。
