Campo Gianluca, Fileti Luca, Valgimigli Marco, Marchesini Jlenia, Scalone Antonella, Ferrari Roberto
Cardiovascular Institute, Azienda Ospedaliera Universitaria S Anna, Ferrara, Italy;
J Blood Med. 2010;1:61-9. doi: 10.2147/JBM.S7236. Epub 2010 May 10.
Nowadays, aspirin (acetylsalicylic acid) and clopidogrel form the cornerstone in prevention of cardiovascular events and their clinical effectiveness has been well established. The thienopyridine clopidogrel is a prodrug that, after hepatic metabolization, strongly inhibits adenosine diphosphate-induced platelet aggregation. Aspirin is a non-steroidal anti-inflammatory drug that exerts its anti-platelet action through the irreversible acetylation of platelet cyclooxygenase (COX)-1, blocking thromboxane A2 production. However, despite dual-antiplatelet therapy, some patients still develop recurrent cardiovascular ischemic events. Many studies have clearly showed that a marked variability exists in the responsiveness to aspirin and clopidogrel, being the poor responder patients at higher risk of short (peri-procedural) and long-term ischemic complications. In particular, these patients showed a major recurrence of myocardial infarction and, after stent implantation, of stent thrombosis. The mechanisms of aspirin and clopidogrel poor response are numerous and not fully elucidated, and are likely multifactorial (eg, genetic polymorphisms, elevated baseline platelet reactivity, drug interaction). How to improve the short- and long-term outcome of these patients is currently unknown. Recently published and ongoing clinical trials are evaluating different strategies for the acute and chronic treatments (eg, reload of clopidogrel, double clopidogrel maintenance dose, switching to prasugrel). In this paper, we reviewed all available evidence on aspirin and clopidogrel resistance and focused our attention on tirofiban, a glycoprotein IIb/IIIa inhibitor that may be used to obtain a better platelet inhibition in poor responder patients during the acute phase and in particular during percutaneous coronary intervention.
如今，阿司匹林（乙酰水杨酸）和氯吡格雷是预防心血管事件的基石，其临床疗效已得到充分证实。噻吩并吡啶类药物氯吡格雷是一种前体药物，经肝脏代谢后，能强烈抑制二磷酸腺苷诱导的血小板聚集。阿司匹林是一种非甾体抗炎药，通过不可逆地乙酰化血小板环氧化酶（COX）-1发挥抗血小板作用，阻断血栓素A2的生成。然而，尽管采用了双联抗血小板治疗，仍有一些患者会发生复发性心血管缺血事件。许多研究清楚地表明，对阿司匹林和氯吡格雷的反应存在显著差异，反应不佳的患者发生短期（围手术期）和长期缺血性并发症的风险更高。特别是，这些患者心肌梗死复发率较高，且在支架植入后发生支架血栓形成的几率也较高。阿司匹林和氯吡格雷反应不佳的机制众多且尚未完全阐明，可能是多因素的（如基因多态性、基线血小板反应性升高、药物相互作用）。目前尚不清楚如何改善这些患者的短期和长期预后。最近发表的以及正在进行的临床试验正在评估急性和慢性治疗的不同策略（如氯吡格雷再负荷、双倍氯吡格雷维持剂量、换用普拉格雷）。在本文中，我们回顾了关于阿司匹林和氯吡格雷抵抗的所有现有证据，并将注意力集中在替罗非班上，它是一种糖蛋白IIb/IIIa抑制剂，可用于在急性期，特别是在经皮冠状动脉介入治疗期间，使反应不佳的患者获得更好的血小板抑制效果。
