Topol E J, Byzova T V, Plow E F
Joseph J Jacobs Center for Thrombosis and Vascular Biology, Department of Cardiology, Cleveland Clinic Foundation, Ohio 44195, USA.
Lancet. 1999 Jan 16;353(9148):227-31. doi: 10.1016/S0140-6736(98)11086-3.
Regardless of the event that stimulates the aggregation of platelets, the receptor alpha(IIb)beta3--one of a family of adhesion receptors known as integrins--has a key role in the process. The past decade has seen the publication of 10 phase III (randomised) clinical trials of four members of a new class of antiplatelet drugs, the GPIIb-IIIa blockers, targeted at this important receptor. Three (abciximab, eptifibatide, and tirofiban) are licensed for human use. 10 other GbIIb-IIIa blockers are in phase II or III human studies. In all 10 placebo-controlled trials, done in the clinical settings of percutaneous coronary intervention or acute coronary syndrome in patients on aspirin, the endpoints favoured the active drug, with a risk reduction for death or non-fatal myocardial infarction of about 21% overall. With attention to heparin dose the risk of bleeding is not a major concern with these agents. The GPIIb-IIIa blockers are taking the clinician and patient out of the era of aspirin monotherapy when platelet inhibition is required.
无论刺激血小板聚集的事件是什么，受体α(IIb)β3（一种被称为整合素的黏附受体家族成员）在这一过程中都起着关键作用。在过去十年中，针对这一重要受体的一类新型抗血小板药物（糖蛋白IIb-IIIa阻滞剂）的四个成员进行了10项III期（随机）临床试验并已发表。其中三种（阿昔单抗、依替巴肽和替罗非班）已获许可用于人类。另外10种糖蛋白IIb-IIIa阻滞剂正处于II期或III期人体研究阶段。在所有10项安慰剂对照试验中，这些试验是在接受阿司匹林治疗的患者进行经皮冠状动脉介入治疗或急性冠状动脉综合征的临床环境中进行的，终点指标有利于活性药物，总体上死亡或非致命性心肌梗死的风险降低了约21%。在关注肝素剂量的情况下，这些药物引起出血的风险并非主要问题。当需要抑制血小板时，糖蛋白IIb-IIIa阻滞剂正将临床医生和患者带出阿司匹林单一疗法的时代。
