Bennett J S
Hematology-Oncology Division, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Annu Rev Med. 2001;52:161-84. doi: 10.1146/annurev.med.52.1.161.
Platelet-inhibitory drugs are of proven benefit to individuals who suffer from atherosclerotic cardiovascular disease. Despite substantial effort to identify more potent platelet-inhibitory agents, aspirin, an irreversible inhibitor of platelet cyclooxygenase activity, remains the standard against which other drugs are judged. Drugs that appear to be at least as efficacious as aspirin in specific clinical settings include the thienopyridines ticlopidine and clopidogrel, specific inhibitors of ADP-stimulated platelet function, and the phosphodiesterase 3 inhibitor cilostazol. Ligand binding to the platelet integrin alphaIIbbeta3 (GPIIb-IIIa), a prerequisite for platelet thrombus formation, has been a prominent target for drug development. Currently, three types of alphaIIbbeta3 antagonists are available: the monoclonal antibody Fab fragment abciximab, cyclic peptides based on the Arg-Gly-Asp (RGD) or related amino acid motifs, and RGD-based peptidomimetics. The efficacy of each type of alphaIIbbeta3 antagonist in the setting of acute coronary artery disease has been confirmed in multicenter clinical trials.
血小板抑制药物已被证明对患有动脉粥样硬化性心血管疾病的个体有益。尽管人们付出了巨大努力来寻找更有效的血小板抑制药物，但阿司匹林作为血小板环氧化酶活性的不可逆抑制剂，仍然是评判其他药物的标准。在特定临床环境中似乎至少与阿司匹林同样有效的药物包括噻吩吡啶类药物噻氯匹定和氯吡格雷（ADP刺激的血小板功能的特异性抑制剂）以及磷酸二酯酶3抑制剂西洛他唑。配体与血小板整合素αIIbβ3（糖蛋白IIb-IIIa）结合是血小板血栓形成的前提条件，一直是药物研发的主要靶点。目前有三种类型的αIIbβ3拮抗剂：单克隆抗体Fab片段阿昔单抗、基于精氨酸-甘氨酸-天冬氨酸（RGD）或相关氨基酸基序的环肽以及基于RGD的拟肽。每种类型的αIIbβ3拮抗剂在急性冠状动脉疾病中的疗效已在多中心临床试验中得到证实。
