Haas S
Klinikum rechts der Isar der Technischen Universität München, Germany.
Vasa. 2009 Feb;38(1):13-29. doi: 10.1024/0301-1526.38.1.13.
Currently available anticoagulants, such as unfractionated heparin, low molecular weight heparins and vitamin K antagonists, have proved effective in the prevention and treatment of thromboembolic disorders. However, these drugs have some drawbacks, such as unpredictability (in the case of unfractionated heparin), non-specificity and parenteral mode of administration, which limit their use in the clinical setting. There is a need for new agents with efficacy similar to that of these classes of anticoagulants and none of their associated drawbacks. Advances are being made in the development of more convenient and more specific drugs, with the aim to improve substantially the prevention and management of thromboembolic disorders. This review will emphasize how the development of an ideal anticoagulant, with potential benefits including high efficacy, safety, low levels of bleeding, fixed dosing, rapid onset of action, ability to bind clot-bound coagulation factors and no requirement for therapeutic monitoring, is a considerable challenge. This review will present the most relevant preclinical data, as well as the clinical studies performed to date, for several drug classes. Direct thrombin inhibitors, such as dabigatran etexilate, will be reviewed, as well as indirect (fondaparinux and idraparinux) and direct (rivaroxaban, apixaban, among others) Factor Xa inhibitors, Factor IXa inhibitors and monoclonal antibodies against Factor IX/IXa.
目前可用的抗凝剂，如普通肝素、低分子量肝素和维生素K拮抗剂，已被证明在预防和治疗血栓栓塞性疾病方面有效。然而，这些药物存在一些缺点，如不可预测性（普通肝素的情况）、非特异性和肠胃外给药方式，这限制了它们在临床环境中的使用。需要开发出疗效与这些类别的抗凝剂相似且无相关缺点的新型药物。在开发更方便、更具特异性的药物方面正在取得进展，目的是大幅改善血栓栓塞性疾病的预防和管理。本综述将强调开发一种理想的抗凝剂是一项相当大的挑战，其潜在益处包括高效、安全、低出血水平、固定剂量、起效迅速、能够结合与凝块结合的凝血因子且无需治疗监测。本综述将介绍几种药物类别的最相关临床前数据以及迄今为止进行的临床研究。将对直接凝血酶抑制剂，如达比加群酯进行综述，以及间接（磺达肝癸钠和依达肝素）和直接（利伐沙班、阿哌沙班等）Xa因子抑制剂、IXa因子抑制剂和抗IX/IXa因子单克隆抗体。
