Herz-Zentrum Bad Krozingen, Bad Krozingen, Germany.
J Am Coll Cardiol. 2010 Jun 1;55(22):2427-34. doi: 10.1016/j.jacc.2010.02.031.
The aim of this study was to evaluate the relative impact of demographic and clinical variables versus the cytochrome P450 2C19 (CYP2C19) polymorphism on antiplatelet effects of clopidogrel.
Platelet responses to clopidogrel show a marked interindividual variability with substantial impact on clinical outcome. Several demographic and clinical characteristics as well as a polymorphism of CYP2C19 have been described as predictors for a low response to clopidogrel.
This analysis enrolled 760 patients undergoing elective coronary stent implantation after loading with 600 mg of clopidogrel. Residual platelet aggregation was determined by optical aggregometry (adenosine diphosphate 5 micromol/l) before discharge. We analyzed the predictive value of the CYP2C19*2 polymorphism and baseline variables for an insufficient antiplatelet response by multivariable regression analysis and classification and regression trees analysis and determined the proportion responsible for the antiplatelet response of these predictors by multivariable linear regression analysis.
Major independent predictors for an insufficient antiplatelet response to clopidogrel were CYP2C192 carrier status (odds ratio [OR]: 2.74; 95% confidence interval [CI]: 1.93 to 3.90) together with age (OR: 1.03; 95% CI: 1.01 to 1.05), diabetes mellitus (OR: 1.75; 95% CI: 1.19 to 2.56), and body mass index (OR: 1.06; 95% CI: 1.02 to 1.11). The classification and regression trees analysis demonstrated that CYP2C192 carrier status followed by diabetes mellitus was the best discriminator between a sufficient and an insufficient antiplatelet response to clopidogrel. The full linear regression model including all these parameters could only explain 11.5% of the antiplatelet response (5.2% by CYP2C19*2 carrier status alone).
Thus, our study does not suggest that, in patients critically dependent on adequate platelet inhibition, genotyping alone or in combination with clinical factors can replace phenotyping of platelet function. (Effect of Clopidogrel Loading and Risk of PCI [EXCELSIOR]; NCT00457236).
本研究旨在评估人口统计学和临床变量与细胞色素 P450 2C19（CYP2C19）多态性对氯吡格雷抗血小板作用的相对影响。
氯吡格雷的血小板反应存在明显的个体间变异性，对临床结果有重大影响。已经描述了几种人口统计学和临床特征以及 CYP2C19 的多态性，作为对氯吡格雷低反应的预测因子。
本分析纳入了 760 例接受 600mg 氯吡格雷负荷治疗后行择期冠状动脉支架植入术的患者。在出院前通过光聚合测定法（二磷酸腺苷 5μmol/L）测定残余血小板聚集。我们通过多变量回归分析和分类回归树分析分析了 CYP2C19*2 多态性和基线变量对氯吡格雷抗血小板反应不足的预测价值，并通过多变量线性回归分析确定了这些预测因子对血小板反应的贡献比例。
对氯吡格雷抗血小板反应不足的主要独立预测因子是 CYP2C192 携带者状态（比值比[OR]：2.74；95%置信区间[CI]：1.93 至 3.90），同时伴有年龄（OR：1.03；95%CI：1.01 至 1.05）、糖尿病（OR：1.75；95%CI：1.19 至 2.56）和体重指数（OR：1.06；95%CI：1.02 至 1.11）。分类回归树分析表明，CYP2C192 携带者状态后紧接着是糖尿病，是区分氯吡格雷抗血小板反应充分与不足的最佳判别因素。包括所有这些参数的完整线性回归模型仅能解释 11.5%的抗血小板反应（仅 CYP2C19*2 携带者状态就占 5.2%）。
因此，我们的研究表明，在严重依赖于充分血小板抑制的患者中，基因分型单独或与临床因素相结合并不能替代血小板功能的表型检测。（氯吡格雷负荷与 PCI 风险[EXCELSIOR]；NCT00457236）。
