Harder Sebastian
Institute of Clinical Pharmacology, Pharmazentrum Frankfurt, University Hospital, Theodor Stern Kai 7, D-60590 Frankfurt am Main, Germany.
Thromb J. 2014 Oct 28;12:22. doi: 10.1186/1477-9560-12-22. eCollection 2014.
Patients with deep vein thrombosis or pulmonary embolism are recommended to receive anticoagulation for acute treatment and secondary prevention of venous thromboembolism (VTE). Fast-acting direct oral anticoagulants, with or without parenteral heparin, have the potential to replace vitamin K antagonists in this setting. Rivaroxaban, a direct Factor Xa inhibitor, is approved in the European Union and the United States for the single-drug treatment of deep vein thrombosis and pulmonary embolism and the secondary prevention of recurrent VTE in adults. The approved rivaroxaban dose schedule (15 mg twice daily for 3 weeks followed by 20 mg once daily) was derived based on pharmacological data from the clinical development programme to achieve a strong antithrombotic effect in the acute treatment phase and address the need to balance efficacy and bleeding risk for long-term treatment with a once-daily dose in the maintenance phase. Data from dose-ranging studies, pharmacokinetic modelling and randomised phase III trials support the use of this regimen. Other direct oral anticoagulants have also shown favourable efficacy and safety compared with standard treatment, and apixaban (European Union) and dabigatran (European Union and United States) have been approved in this indication. There are practical aspects to rivaroxaban use that must be considered, such as treatment of patients with renal and hepatic impairment, drug-drug interactions, monitoring of effect and management of bleeding. This review discusses the derivation of the VTE treatment regimen for rivaroxaban, summarises the clinical data for rivaroxaban and other direct oral anticoagulants in VTE treatment, and considers the practical aspects of rivaroxaban use in this setting.
对于深静脉血栓形成或肺栓塞患者，建议接受抗凝治疗以进行急性治疗和静脉血栓栓塞症（VTE）的二级预防。速效直接口服抗凝剂，无论是否联合胃肠外肝素，都有可能在此情况下替代维生素K拮抗剂。利伐沙班是一种直接的Xa因子抑制剂，在欧盟和美国被批准用于单药治疗深静脉血栓形成和肺栓塞以及成人复发性VTE的二级预防。批准的利伐沙班剂量方案（前3周每日两次，每次15mg，之后每日一次，每次20mg）是根据临床开发项目的药理学数据得出的，以在急性治疗阶段实现强大的抗血栓形成作用，并满足在维持阶段用每日一次剂量平衡长期治疗的疗效和出血风险的需求。剂量范围研究、药代动力学建模和随机III期试验的数据支持该方案的使用。与标准治疗相比，其他直接口服抗凝剂也显示出良好的疗效和安全性，阿哌沙班（欧盟）和达比加群（欧盟和美国）已被批准用于此适应症。使用利伐沙班时必须考虑一些实际问题，例如肾和肝功能损害患者的治疗、药物相互作用、疗效监测和出血管理。本综述讨论了利伐沙班VTE治疗方案的推导，总结了利伐沙班和其他直接口服抗凝剂在VTE治疗中的临床数据，并考虑了在此情况下使用利伐沙班的实际问题。
