《国际循环》：氯吡格雷抵抗可能是更强化的抗血小板策略以及开发新型强效药一个理由。氯吡格雷抵抗和心血管结果之间有何关联？
　　<International Circulation> :Clopidogrel resistance may be a justification for more aggressive antiplatelet regimens and development of new more potent drugs. What is the relationship between clopidogrel resistance and cardiovascular outcome?

　　Dr Weitz：我们知道，与氯吡格雷活性欠佳相关的基因突变的患者经皮冠状动脉介入后的预后较差，但我们不知道当这种患者只是接受药物治疗时他们的预后是否也较差。在冠状动脉介入后血小板被最大激活时所发生的事情与患者接受药物治疗且血小板活性较低时所发生的事情看来存在一些差异。在接受介入的患者中，似乎需要非常好的抗小血板治疗，，且这是基因突变所致的差异。对那些接受药物治疗可能不需要如此强化的抗血小板治疗的患者，基因突变是否可能不那么重要。关于这个问题，我们仍需要更多地了解，但在某些患者中所观察到的血小板反应增强的背后，影响氯吡格雷活性的不止是这些基因突变。很可能有多种因素涉及这一问题，因此它取决于你如何定义氯吡格雷抵抗。你是根据基因突变、根据基因分型并寻找与氯吡格雷活性欠佳相关的基因型来定义它？或者你是根据观察增强的血小板反应的基因分型来定义它？在这种病例中血小板反应增强可能有多种原因，其中仅一些可能与氯吡格雷有关。

　　Dr Weitz: We know that patients who have genetic mutations that are associated with poor activation of clopidogrel have a worse outcome after percutaneous coronary interventions， but we don’t know whether such patients have a worse outcome when they are managed medically. There seems to be some discrepancy between what happens after coronary interventions when platelets are maximally activated and what happens when patients are medically managed where presumably platelet activation is less. In the patients who undergo interventions， it looks like very good platelet blockade is needed and that is where genetic mutations can make a difference. For those that are medically managed， where perhaps we don’t need such aggressive platelet inhibition， it may not matter so much whether these mutations are present or not. We still need to learn more about this problem.  However， we do know that the increased platelet reactivity that is found in some patients despite dual antiplatelet therapy is the result of more than just the genetic mutations that influence clopidogrel activation.  There are probably a variety of factors that influence platelet reactivity:  Therefore， do you define clopidogrel resistance by genotype and look for the genotypes that are associated with poor clopidogrel activation?  Or do you define it by phenotype and measure platelet reactivity， which can be influenced by multiple factors， only some of which may be related to clopidogrel?  Therefore， it depends on how you define clopidogrel resistance. 

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