Department of Medicine, Griffin Hospital, Derby, CT, USA.
Am J Ther. 2012 Nov;19(6):465-9. doi: 10.1097/MJT.0b013e3181ff7c16.
Currently available antiplatelet agents have shown improved short- and long-term clinical outcomes but are associated with increased bleeding risk, and the rates of recurrent ischemic events still remain high. Selective inhibition of protease-activated receptor-1 for thrombin represents a potential novel strategy to reduce ischemic events without increasing the risk of bleeding. Two protease-activated receptor-1 antagonists are currently being evaluated in clinical trials: SCH 530348 and E5555. Results of phase II trials have shown that SCH 530348, when added to standard antiplatelet therapy, was well tolerated and not associated with increased bleeding risk. Two large-scale phase III trials assessing the efficacy of SCH 530348 in addition to the standard of care are currently ongoing. This review provides an outline of the current status of understanding on platelet thrombin-receptor antagonist SCH 530348, focusing on its pharmacologic properties and clinical development.
目前可用的抗血小板药物已显示出改善短期和长期临床结局的效果，但与出血风险增加相关，而复发性缺血事件的发生率仍然很高。特异性抑制凝血酶的蛋白酶激活受体-1可能是一种减少缺血事件而不增加出血风险的新策略。目前正在两项临床试验中评估两种蛋白酶激活受体-1拮抗剂：SCH 530348 和 E5555。二期临床试验结果表明，SCH 530348 联合标准抗血小板治疗具有良好的耐受性，并且不增加出血风险。目前正在进行两项大型三期临床试验，评估 SCH 530348 联合标准治疗的疗效。本文综述了血小板凝血酶受体拮抗剂 SCH 530348 的理解现状，重点介绍其药理特性和临床开发。
