Department of Internal Medicine, Division of Angiology and Haemostasis, University Hospitals of Geneva, CH 1211 Geneva 14, Switzerland.
Pharmacol Ther. 2011 Apr;130(1):46-58. doi: 10.1016/j.pharmthera.2010.12.007. Epub 2010 Dec 24.
Thromboembolic disorders are among the major causes of morbidity and mortality, and anticoagulation remains the cornerstone of prevention and treatment of these disorders. Although effective, the well-established agents have significant drawbacks. Heparin, low molecular weight heparin, and fondaparinux must be given parenterally, which is inconvenient for long-term or home use. The orally administered vitamin K antagonists (such as warfarin) have a slow onset of action, thus requiring bridging therapy with a parenteral agent when immediate anticoagulation is needed (e.g. inpatients with acute deep vein thrombosis). Because vitamin K antagonists produce a variable anticoagulant response as a result of multiple drug-drug and food-drug interactions and genetic polymorphisms, frequent coagulation monitoring and dose adjustment are required to ensure a therapeutic level of anticoagulation, which is inconvenient for both patients and physicians. In the search for new agents to overcome the drawbacks associated with traditional agents, direct Factor Xa inhibitors (e.g. rivaroxaban, apixaban, and edoxaban) and direct thrombin inhibitors (e.g. dabigatran etexilate) have been developed and are undergoing late-stage clinical evaluation for the prevention and treatment of thromboembolic disorders. These new oral agents have already shown promise in large-scale clinical studies and data suggest that we have entered a new era with novel drugs that are closer than ever to the 'ideal anticoagulant'. Because these new oral agents have a rapid onset of action and can be given at fixed doses without the need for routine coagulation monitoring, they may simplify treatment paradigms and are expected to improve overall clinical outcome.
血栓栓塞性疾病是导致发病率和死亡率的主要原因之一，抗凝治疗仍然是预防和治疗这些疾病的基石。虽然有效，但已确立的药物存在明显的缺点。肝素、低分子量肝素和磺达肝素必须通过注射给药，这对于长期或家庭使用来说不太方便。口服维生素 K 拮抗剂（如华法林）起效缓慢，因此在需要立即抗凝时需要桥接治疗，例如急性深静脉血栓形成的住院患者。由于维生素 K 拮抗剂由于多种药物相互作用和遗传多态性导致抗凝反应不稳定，需要频繁进行凝血监测和剂量调整，以确保达到治疗水平的抗凝，这对患者和医生都不方便。为了寻找克服传统药物缺点的新药物，已经开发出直接 Xa 因子抑制剂（如利伐沙班、阿哌沙班和依度沙班）和直接凝血酶抑制剂（如达比加群酯），并正在进行血栓栓塞性疾病预防和治疗的晚期临床评估。这些新的口服药物已经在大规模临床研究中显示出前景，并且数据表明我们已经进入了一个新时代，拥有比以往任何时候都更接近“理想抗凝剂”的新型药物。由于这些新的口服药物起效迅速，可以固定剂量给药，无需常规凝血监测，因此可能会简化治疗方案，并有望改善整体临床结局。
