Ahrens Ingo, Smith Belinda K, Bode Christoph, Peter Karlheinz
Baker Heart Research Institute, Centre for Thrombosis and Myocardial Infarction, Melbourne, VIC 8008, Australia.
Expert Opin Drug Metab Toxicol. 2007 Aug;3(4):609-20. doi: 10.1517/17425225.3.4.609.
Antithrombotic therapy is a crucial component of interventional cardiology and currently involves the administration of both anticoagulant and antiplatelet agents. The implementation of standard dual or triple antiplatelet therapies has allowed percutaneous coronary intervention (PCI) with stent implantation to become the treatment of choice in most patients with acute coronary syndromes (ACS), particularly in patients with ST-segment elevation myocardial infarction. However, the combined use of antithrombotic agents increases the bleeding risk associated with coronary intervention, which is a concern due to the increasing evidence that bleeding complications are associated with a higher risk of ischaemic events and death. The shortcomings of currently available anticoagulant drugs have promoted the ongoing development of new, powerful anticoagulant agents that have both efficacy in the setting of PCI and a reduced risk of bleeding; one of these classes of agents targets the thrombin molecule, a key factor in the coagulation cascade, and belongs to the class of anticoagulants known as direct thrombin inhibitors (DTIs). Bivalirudin, a synthetic peptide, is a DTI with unique, favourable pharmacological properties that include predictable linear pharmacokinetics. Bivalirudin was approved as an anticoagulant in patients undergoing routine PCI in 2000 by the FDA (in 2004 in Europe and Australia) and more recently in patients with ACS undergoing PCI. The pharmacological properties of bivalirudin, along with current indications for its use, are discussed in this review, with a focus on the major completed and ongoing clinical trials with bivalirudin.
抗栓治疗是介入心脏病学的关键组成部分,目前涉及抗凝剂和抗血小板药物的联合使用。标准的双联或三联抗血小板治疗的实施,使得经皮冠状动脉介入治疗(PCI)并植入支架成为大多数急性冠状动脉综合征(ACS)患者,尤其是ST段抬高型心肌梗死患者的首选治疗方法。然而,抗栓药物的联合使用增加了与冠状动脉介入相关的出血风险,鉴于越来越多的证据表明出血并发症与缺血事件和死亡风险较高相关,这一问题备受关注。现有抗凝药物的缺点推动了新型强效抗凝剂的不断研发,这些抗凝剂在PCI治疗中既有效又能降低出血风险;其中一类药物作用于凝血级联反应中的关键因子——凝血酶分子,属于直接凝血酶抑制剂(DTI)类抗凝剂。比伐芦定是一种合成肽,是一种具有独特、良好药理学特性的DTI,包括可预测的线性药代动力学。2000年,比伐芦定被美国食品药品监督管理局批准用于接受常规PCI的患者(2004年在欧洲和澳大利亚获批),最近又被批准用于接受PCI的ACS患者。本文综述了比伐芦定的药理学特性及其目前的使用指征,重点介绍了比伐芦定已完成和正在进行的主要临床试验。