De Miguel Antonio, Ibanez Borja, Badimón Juan José
Atherothrombosis Research Unit, The Zena and Michael A Wiener Cardiovascular Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
Thromb Haemost. 2008 Aug;100(2):196-203.
The benefits of clopidogrel in the treatment and prevention of coronary artery disease are well established, however, not all individuals respond in the same way to clopidogrel; there are patients who suffer adverse events despite clopidogrel treatment. This review focuses on the definition, potential mechanisms for and clinical implications of clopidogrel resistance, as well as the strategies to improve the response to this antiplatelet drug. There is an inter-individual variability in response to clopidogrel therapy, and a sub-optimal response (clopidogrel resistance) has been associated with adverse cardiovascular events. Nevertheless, there is no clear and consensual definition of clopidogrel resistance. Response to clopidogrel therapy follows a normal, bell-shaped distribution, so a more appropriate description would be variable response rather than clopidogrel resistance. Independent of the term used, lower response to clopidogrel therapy seems to be associated with a higher probability of suffering thrombotic events. Due to the misleading definition of resistance and non-standardized method for assessing platelet inhibition, current guidelines do not recommend the use of platelet function assays to monitor the inhibitory effect of antiplatelet drugs. Current guidelines also do not recommend clopidogrel loading doses higher than 300 mg and daily maintenance doses higher than 75 mg, even though a regimen of 600 mg clopidogrel loading dose seems to be preferred for patients undergoing percutaneous coronary interventions.
氯吡格雷在治疗和预防冠状动脉疾病方面的益处已得到充分证实，然而，并非所有个体对氯吡格雷的反应都相同；有些患者尽管接受了氯吡格雷治疗，但仍会出现不良事件。本综述重点关注氯吡格雷抵抗的定义、潜在机制和临床意义，以及改善对这种抗血小板药物反应的策略。个体对氯吡格雷治疗的反应存在差异，而次优反应（氯吡格雷抵抗）与不良心血管事件相关。然而，目前对于氯吡格雷抵抗尚无明确且一致认可的定义。对氯吡格雷治疗的反应呈正态钟形分布，因此更恰当的描述应为可变反应而非氯吡格雷抵抗。无论使用何种术语，对氯吡格雷治疗反应较低似乎与发生血栓事件的较高概率相关。由于抵抗的定义存在误导性且评估血小板抑制的方法未标准化，当前指南不建议使用血小板功能检测来监测抗血小板药物的抑制效果。当前指南也不推荐氯吡格雷负荷剂量高于300mg以及每日维持剂量高于75mg，尽管对于接受经皮冠状动脉介入治疗的患者，600mg氯吡格雷负荷剂量方案似乎更受青睐。
