Bauer Kenneth A
1Beth Israel Deaconess Medical Center and VA Boston Healthcare System, Department of Medicine, Harvard Medical School, Boston, MA.
Hematology Am Soc Hematol Educ Program. 2013;2013:464-70. doi: 10.1182/asheducation-2013.1.464.
The availability of new oral anticoagulants (NOACs) targeting either thrombin (dabigatran etexilate) or factor Xa (rivaroxaban and apixaban) for the prevention and treatment of thrombosis has been highly anticipated. NOACs have major pharmacologic advantages over vitamin K antagonists (eg, warfarin), including rapid onset/offset of action, few drug interactions, and predictable pharmacokinetics, eliminating the requirement for regular coagulation monitoring. Regulatory agencies have approved several NOACs for specific indications based on the results of clinical trials demonstrating efficacy and safety that are at least as good, if not better, than warfarin (for stroke prevention in atrial fibrillation and treatment and secondary prevention of venous thromboembolism) or low-molecular-weight heparin, which is injectable (for initial treatment of venous thromboembolism and thromboprophylaxis in patients undergoing hip or knee arthroplasty). However, the adoption of this new therapeutic class into clinical practice has been slower than expected due to several factors including concerns regarding medication adherence without laboratory monitoring, uncertainty about dosing in some patient populations (eg, renal dysfunction, marked extremes of body weight), and higher drug costs compared with warfarin. Other issues are the current absence of specific antidotes for NOACs and assays to measure drug levels at most centers. The indications for NOACs on the market will expand and at least one additional agent (edoxaban) will likely gain approval within the next 2 years. As practitioners gain familiarity with the drugs and healthcare systems adapt to their use, NOAC use will increase substantially over time. Warfarin, however, will continue to be an appropriate anticoagulant choice for many patients.
新型口服抗凝药(NOACs)可靶向凝血酶(达比加群酯)或Xa因子(利伐沙班和阿哌沙班),用于预防和治疗血栓形成,这一进展备受期待。与维生素K拮抗剂(如华法林)相比,NOACs具有显著的药理学优势,包括起效/失效迅速、药物相互作用少以及药代动力学可预测,无需定期进行凝血监测。基于临床试验结果显示其疗效和安全性至少与华法林相当(用于房颤的卒中预防以及静脉血栓栓塞的治疗和二级预防)或优于低分子肝素(用于静脉血栓栓塞的初始治疗以及髋关节或膝关节置换术患者的血栓预防,低分子肝素为注射用药),监管机构已批准数种NOACs用于特定适应证。然而,由于多种因素,包括担心无实验室监测时的用药依从性、某些患者群体(如肾功能不全、体重极端异常者)给药的不确定性以及与华法林相比更高的药物成本,这一新型治疗类别在临床实践中的应用比预期要慢。其他问题包括目前多数中心缺乏NOACs的特异性解毒剂以及测量药物水平的检测方法。市场上NOACs的适应证将会扩大,至少一种额外的药物(依度沙班)可能在未来两年内获得批准。随着从业者对这些药物越来越熟悉以及医疗保健系统适应其使用,随着时间推移,NOACs的使用将大幅增加。然而,华法林对许多患者而言仍将是一种合适的抗凝选择。