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Investigating Real‐World Clopidogrel Pharmacogenetics in Stroke Using a Bioresource Linked to Electronic Medical Records

机译:使用链接到电子病历的生物资源调查现实世界中的氯吡格雷药物遗传学

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摘要

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%). CYP2C19*2 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 CYP2C19*2 on clopidogrel efficacy using a purely EMR approach. This suggests that the risk in the ischemic stroke population may be particularly high.
机译:氯吡格雷的疗效受细胞色素P450(CYP)2C19遗传变异的影响,但是,很少有研究考虑患有中风的患者。我们使用与生物资源链接的电子病历(EMR)来检查氯吡格雷药物遗传学在卒中中的现实意义。因任何动脉血栓闭塞(ATO)事件住院治疗且随后在社区中兑换氯吡格雷处方的患者进入研究(n = 651)。在24个月的随访期间,ATO复发或死亡的主要终点发生在299例患者中(46%)。 CYP2C19 * 2功能丧失的等位基因携带者发生风险增加(危险比(HR)= 1.29; 95%置信区间(CI)= 1.04-1.59; P = 0.019)。在缺血性卒中亚组(n = 94)中,风险的估计值更大(HR = 2.23; 95%CI = 1.17–4.24; P = 0.015),这得到现有研究的荟萃分析的进一步支持。总之,我们已经证明了使用纯EMR方法研究CYP2C19 * 2对氯吡格雷疗效的临床影响。这表明缺血性中风人群的风险可能特别高。

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