Duke Clinical Research Institute, Duke University Medical Center, 2400 Pratt Street, Room 0311 Terrace Level, Durham, NC 27705, USA.
Curr Cardiol Rep. 2012 Feb;14(1):32-9. doi: 10.1007/s11886-011-0232-z.
Platelet activation is a key process in the pathogenesis of acute coronary syndromes (ACS). Of the many triggers involved in this process, three are presumed to be critical: thromboxane A(2) (TBXA(2)) via the TBXA(2) receptor, adenosine diphosphate via the P2Y(12) receptor, and thrombin via the protease-activated receptor (PAR)-1. Despite the effective inhibition of the first two pathways with aspirin and an expanding family of P2Y(12) inhibitors, the incidence of recurrent ischemic events remains high after ACS. PAR-1 inhibitors are a novel class of antiplatelet agents that inhibit thrombin-mediated platelet activation. Preclinical data and phase 2 clinical trials in patients with stable and unstable coronary disease support the potential of these compounds to improve clinical outcome. In this review we discuss the rationale for developing this novel class of agents with a focus on the two compounds in most advanced clinical development, vorapaxar (SCH 530348) and atopaxar (E5555).
血小板激活是急性冠脉综合征（ACS）发病机制中的一个关键过程。在这个过程涉及到的许多触发因素中，有三个被认为是关键的：血栓素 A2（TBXA2）通过 TBXA2 受体、二磷酸腺苷通过 P2Y12 受体和凝血酶通过蛋白酶激活受体（PAR）-1。尽管使用阿司匹林和不断扩大的 P2Y12 抑制剂家族有效抑制了前两种途径，但 ACS 后复发性缺血事件的发生率仍然很高。PAR-1 抑制剂是一类新型的抗血小板药物，可抑制凝血酶介导的血小板激活。稳定和不稳定型冠心病的临床前数据和 2 期临床试验支持这些化合物改善临床结局的潜力。在这篇综述中，我们讨论了开发这一类新型药物的基本原理，并重点介绍了两种处于最先进临床开发阶段的化合物，vorapaxar（SCH 530348）和 atopaxar（E5555）。
