Janssen Research & Development, LLC, Raritan, New Jersey 08869, USA.
Ann N Y Acad Sci. 2013 Jul;1291:42-55. doi: 10.1111/nyas.12136. Epub 2013 May 23.
The development of rivaroxaban (XARELTO®) is an important new medical advance in the field of oral anticoagulation. Thrombosis-mediated conditions constitute a major burden for patients, healthcare systems, and society. For more than 60 years, the prevention and treatment of these conditions have been dominated by oral vitamin K antagonists (such as warfarin) and the injectable heparins. Thrombosis can lead to several conditions, including deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke, and/or death. Prevention and treatment of thrombosis with an effective, convenient-to-use oral anticoagulant with a favorable safety profile is critical, especially in an aging society in which the risk of thrombosis, and the potential for bleeding complications, is increasing. Rivaroxaban acts to prevent and treat thrombosis by potently inhibiting coagulation Factor Xa in the blood. Factor Xa converts prothrombin to thrombin, which initiates the formation of blood clots by converting fibrinogen to clot-forming fibrin and leads to platelet activation. After a large and novel clinical development program in over 75,000 patients to date, rivaroxaban has received approval for multiple indications in the United States, European Union, and other countries worldwide to prevent and treat several thrombosis-mediated conditions. This review will highlight some of the unique aspects of the rivaroxaban development program.
利伐沙班（拜瑞妥®）的研发是口服抗凝领域的一项重要医学新进展。血栓介导的疾病给患者、医疗体系和社会带来了沉重负担。六十多年来，这些疾病的预防和治疗一直以口服维生素 K 拮抗剂（如华法林）和注射用肝素为主。血栓可导致多种疾病，包括深静脉血栓、肺栓塞、心肌梗死、中风和/或死亡。预防和治疗血栓的有效、使用方便的口服抗凝剂，且具有良好的安全性至关重要，尤其是在老龄化社会中，血栓形成的风险以及出血并发症的潜在风险都在增加。利伐沙班通过强力抑制血液中的凝血因子 Xa 来发挥预防和治疗血栓的作用。凝血因子 Xa 将凝血酶原转化为凝血酶，凝血酶通过将纤维蛋白原转化为形成血栓的纤维蛋白来启动血栓形成，并导致血小板活化。在目前已对超过 75000 名患者进行了大型和新颖的临床开发项目之后，利伐沙班已在美国、欧盟和世界其他国家获得批准，用于预防和治疗多种血栓介导的疾病。这篇综述将重点介绍利伐沙班研发项目的一些独特方面。
