OBJECTIVES To assess the prevalence of high on-clopidogrel platelet reactivity (HCPR) in patients with ischaemic stroke or transient ischaemic attack (IS/TIA), their outcome and genetic basis of on-treatment response variability in IS/TIA patients. METHODS We conducted a comprehensive search of PubMed and EMBASE from their inceptions to March 9, 2019. Studies that reported absolute numbers/percentages of HCRP at any time point after IS/TIA onset evaluated with any type of platelet function tests, clinical outcomes and genotyping data were included. RESULTS Among 21 studies of 4312 IS/TIA patients treated with clopidogrel, the pooled prevalence of HCPR was 28% (95%CI: 24-32%; high heterogeneity: I2 = 88.2%, p < 0.001). Heterogeneity degree diminished across groups defined by the HCPR testing method. Clopidogrel non-responder IS/TIA patients had poorer outcome compared to responders (RR = 2.09, 95%CI: 1.61-2.70; p = 0.036; low heterogeneity across studies: I2 = 27.4%, p = 0.210). IS/TIA carriers of CYP2C19*2 or CYP2C19*3 loss of function alleles had a higher risk of HCPR compared to wild type (RR = 1.69, 95%CI: 1.47-1.95; p < 0.001; I2 = 0.01%, p = 0.475). CONCLUSIONS This systematic review shows a high prevalence of clopidogrel resistance in IS/TIA and poor outcome in these patients. CYP2C19 polymorphisms may potentially influence clopidogrel resistance.

中文翻译：

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缺血性中风或短暂性脑缺血发作中氯吡格雷的高血小板反应性：系统评价和荟萃分析。

目的评估缺血性中风或短暂性脑缺血发作（IS / TIA）患者的高氯吡格雷血小板反应性（HCPR）的患病率，其结局以及IS / TIA患者治疗中反应变异性的遗传基础。方法我们对从PubMed和EMBASE成立至2019年3月9日的内容进行了全面搜索。研究报告了IS / TIA发作后任何时间点的HCRP绝对数/百分比，并通过任何类型的血小板功能测试，临床结果和基因分型进行了评估数据包括在内。结果在对4312名接受氯吡格雷治疗的IS / TIA患者的21项研究中，合并的HCPR患病率为28％（95％CI：24-32％；高度异质性：I2 = 88.2％，p <0.001）。HCPR测试方法定义的各组之间的异质性程度有所降低。与反应者相比，氯吡格雷无反应者IS / TIA患者的预后较差（RR = 2.09，95％CI：1.61-2.70； p = 0.036；研究间异质性低：I2 = 27.4％，p = 0.210）。CYP2C19 * 2或CYP2C19 * 3功能丧失的等位基因的IS / TIA携带者与野生型相比具有较高的HCPR风险（RR = 1.69，95％CI：1.47-1.95; p <0.001; I2 = 0.01％，p = 0.475）。结论这项系统评价显示IS / TIA中氯吡格雷耐药的发生率很高，而这些患者的预后较差。CYP2C19基因多态性可能会影响氯吡格雷抵抗。0.001；I2 = 0.01％，p = 0.475）。结论这项系统评价显示IS / TIA中氯吡格雷耐药的发生率很高，而这些患者的预后较差。CYP2C19基因多态性可能会影响氯吡格雷抵抗。0.001；I2 = 0.01％，p = 0.475）。结论这项系统评价显示IS / TIA中氯吡格雷耐药的发生率很高，而这些患者的预后较差。CYP2C19基因多态性可能会影响氯吡格雷抵抗。