Marczewski Margaret M, Postula Marek, Kosior Dariusz
Department of Cardiology, Central University Hospital, and Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland.
Vasc Health Risk Manag. 2010 Jun 1;6:419-29. doi: 10.2147/vhrm.s7054.
Atherothrombosis, thrombus formation as a result of atherosclerotic plaque rupture, is a major modern health problem, often underlying coronary artery disease, stroke, and peripheral arterial disease. After the treatment of an acute thrombotic episode, long-term therapy is warranted as a secondary prophylaxis of such events and their complications. Because of the importance of platelets' involvement in the initiation and propagation of thrombosis, antiplatelet drugs have come to the forefront of atherothrombotic disease treatment. Dual antiplatelet therapy of aspirin plus clopidogrel--the current standard--has its benefits, but it also has its limitations with regard to its pharmacologic properties and adverse effects. For these reasons, within the last decade or so, the investigation of novel antiplatelet agents has prospered. Here, we review the main pathways through which platelets participate in acute thrombosis and the interruption of these pathways by using novel antiplatelet agents, including P2Y12 receptor antagonists (the recently approved prasugrel, the probable next-in-line ticagrelor, and others). The need for a more individualized patient therapy is evident; although most of the aforementioned pharmaceuticals have the potential to contribute to this, their clinical utility remains to be seen.
动脉粥样硬化血栓形成,即由于动脉粥样硬化斑块破裂导致的血栓形成,是一个主要的现代健康问题,常常是冠状动脉疾病、中风和外周动脉疾病的潜在病因。在急性血栓事件得到治疗后,需要进行长期治疗以作为此类事件及其并发症的二级预防。由于血小板在血栓形成的起始和传播过程中具有重要作用,抗血小板药物已成为动脉粥样硬化血栓形成疾病治疗的前沿药物。阿司匹林加氯吡格雷的双重抗血小板治疗——目前的标准治疗方法——有其益处,但在药理特性和不良反应方面也有其局限性。由于这些原因,在过去十年左右的时间里,新型抗血小板药物的研究蓬勃发展。在此,我们综述血小板参与急性血栓形成的主要途径以及使用新型抗血小板药物(包括P2Y12受体拮抗剂,如最近获批的普拉格雷、可能的下一代替格瑞洛等)对这些途径的阻断作用。显然需要更个体化的患者治疗;尽管上述大多数药物都有潜力为此做出贡献,但其临床效用仍有待观察。