Gurbel Paul A, Lau Wei C, Bliden Kevin P, Tantry Udaya S
Sinai Center for Thrombosis Research, Baltimore, Maryland 21215, USA.
Curr Pharm Des. 2006;12(10):1261-9. doi: 10.2174/138161206776361345.
Clopidogrel, in combination wih aspirin, is currently the drug of choice to prevent thrombosis after coronary stent implantation. Currently, clopidogrel is administered to the vast majority of patients without any assessment of platelet inhibition. Response variability and resistance, however, definitely occur to clopidogrel treatment. Preliminary data support the hypothesis that patients with reactive or clopidogrel nonresponsive platelets are at risk for thrombotic events. However, the magnitude of the clinical effect remains unknown and relationship between nonresponsiveness and risk of clinical events is under-investigated. Several important questions that must be answered are: A) What is the relation of clopidogrel resistance and high platelet reactivity to the occurrence of stent thrombosis, recurrent myocardial infarction, stroke and death?; B) Is there a threshold of platelet reactivity that correlates with the onset of thrombotic risk?; and C) What is the cost of administering clopidogrel to non-responsive patients? Finally, our understanding of the clinical relevance of drug resistance and high platelet reactivity should be facilitated by the use of validated point-of-service devices. The mechanisms of the response variability to clopidogrel remain incompletely defined. The contribution of intra- and extracellular pathways are under investigation.
氯吡格雷与阿司匹林联合使用，是目前冠状动脉支架植入术后预防血栓形成的首选药物。目前，绝大多数患者在未对血小板抑制进行任何评估的情况下就使用氯吡格雷。然而，氯吡格雷治疗确实会出现反应变异性和抵抗现象。初步数据支持这样的假说，即血小板反应性高或对氯吡格雷无反应的患者存在血栓形成事件的风险。然而，临床效应的程度尚不清楚，且无反应性与临床事件风险之间的关系研究不足。几个必须回答的重要问题是：A）氯吡格雷抵抗和高血小板反应性与支架血栓形成、复发性心肌梗死、中风和死亡的发生有何关系？B）是否存在与血栓形成风险发作相关的血小板反应性阈值？C）给无反应患者使用氯吡格雷的成本是多少？最后，使用经过验证的即时检测设备应有助于我们理解药物抵抗和高血小板反应性的临床相关性。氯吡格雷反应变异性的机制仍未完全明确。细胞内和细胞外途径的作用正在研究中。
