Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
Cardiol Rev. 2012 Sep-Oct;20(5):209-21. doi: 10.1097/CRD.0b013e3182503e2d.
Vitamin K antagonists (VKAs) such as warfarin have traditionally been the major therapeutic option for anticoagulation in clinical practice. VKAs are effective and extensively recommended for the prevention of venous and arterial thromboembolism in cardiovascular disease. Despite its effectiveness, warfarin is limited by factors such as a narrow therapeutic index, drug-drug interactions, food interactions, slow onset and offset of action, hemorrhage, and routine anticoagulation monitoring to maintain therapeutic international normalized ratio. During the last 2 decades, the approval of anticoagulants, such as low-molecular-weight heparins, indirect factor Xa inhibitors (eg, fondaparinux), and direct thrombin inhibitors (eg, argatroban, lepirudin, and desirudin), have expanded the number of available antithrombotic compounds with additional targets within the anticoagulation pathway. Although these medications offer several potential therapeutic advantages, they all require parenteral or subcutaneous administration and are substantially more expensive than VKAs. Thus, VKAs, despite several limitations, have remained the major option for most patients requiring chronic anticoagulation. These limitations have prompted interest in the development of newer oral anticoagulants. Novel anticoagulants targeting inhibition of factor Xa and thrombin (factor IIa) have now been incorporated into clinical practice based on the results of large randomized clinical trials, with the recent U.S. Food and Drug Administration approval of dabigatran for stroke prevention in atrial fibrillation and rivaroxaban for deep vein thrombosis and stroke prevention in atrial fibrillation, with multiple other agents in various stages of development for these and other indications. This review discusses the pharmacological properties, clinical results, and therapeutic applications of novel and new anticoagulants, thereby providing an outline for the future of anticoagulation in cardiovascular disease.
维生素 K 拮抗剂（VKAs），如华法林，一直以来都是临床抗凝治疗的主要选择。VKAs 对于预防心血管疾病中的静脉和动脉血栓栓塞非常有效，并被广泛推荐。尽管华法林有效，但由于治疗指数较窄、药物相互作用、食物相互作用、作用起效和消除缓慢、出血以及常规抗凝监测以维持治疗国际标准化比值等因素，其应用受到限制。在过去的 20 年中，批准了抗凝药物，如低分子量肝素、间接因子 Xa 抑制剂（如磺达肝素）和直接凝血酶抑制剂（如阿加曲班、来匹卢定和地西卢定），增加了可用的抗血栓化合物数量，并增加了抗凝途径内的额外靶点。尽管这些药物具有一些潜在的治疗优势，但它们都需要肠外或皮下给药，而且比 VKAs 昂贵得多。因此，尽管 VKAs 存在一些局限性，但仍然是大多数需要长期抗凝的患者的主要选择。这些局限性促使人们对新型口服抗凝剂的开发产生了兴趣。新型抗凝剂针对因子 Xa 和凝血酶（因子 IIa）的抑制作用，现已基于大型随机临床试验的结果在临床实践中得到应用，最近美国食品和药物管理局批准达比加群用于预防心房颤动的中风，以及利伐沙班用于预防深静脉血栓形成和心房颤动的中风，还有多种其他药物处于这些和其他适应症的不同开发阶段。本文讨论了新型和新抗凝剂的药理学特性、临床结果和治疗应用，从而为心血管疾病中的抗凝未来提供了概述。
