Uchiyama Shinichiro
Department of Neurology, Tokyo Women's Medical University.
Rinsho Shinkeigaku. 2011 Nov;51(11):1004-6. doi: 10.5692/clinicalneurol.51.1004.
Dabigatran is a direct thrombin inhibitor, does not require blood coagulation monitoring and limitation of vitamin K intake as well as very few drug interactions, and thus expected to be an oral anticoagulant alternative to warfarin. Randomized Evaluation of Long Term Anticoagulant Therapy (RE-LY) was conducted to determine non-inferiority of dabigatran against warfarin as an international multicenter-cooperative randomized trial in patients with non-valvular atrial fibrillation (NVAF). The results showed not only non-inferiority of dabigatran but also superiority of high-dose dabigatran in efficacy and of low-dose dabigatran in safety. In a sub-analysis of RE-LY in NVAF patients with history of stroke or TIA, who are at high risk of intracranial hemorrhage with anticoagulants, hemorrhagic stroke was much less frequent in patients on either dose of dabigatran than in those on warfarin. In a sub-analysis of RE-LY in Japanese patients with NVAF, the results showed a consistency of the efficacy and safety profiles of dabigatran with the results of the global RE-LY trial. Use of dabigatran should be contraindicated in NVAF patients with renal insufficiency because some cases with fatal bleeding have been reported in a post marketing survey.
达比加群是一种直接凝血酶抑制剂，无需进行凝血监测，也无需限制维生素K的摄入量，且药物相互作用极少，因此有望成为华法林的口服抗凝替代药物。长期抗凝治疗随机评估（RE-LY）试验作为一项针对非瓣膜性心房颤动（NVAF）患者的国际多中心合作随机试验，旨在确定达比加群相对于华法林的非劣效性。结果显示，达比加群不仅具有非劣效性，而且高剂量达比加群在疗效方面具有优越性，低剂量达比加群在安全性方面具有优越性。在RE-LY试验针对有卒中或短暂性脑缺血发作（TIA）病史的NVAF患者进行的亚组分析中，这些患者使用抗凝剂时发生颅内出血的风险较高，服用任一剂量达比加群的患者发生出血性卒中的频率均远低于服用华法林的患者。在RE-LY试验针对日本NVAF患者进行的亚组分析中，结果显示达比加群的疗效和安全性与全球RE-LY试验的结果一致。对于肾功能不全的NVAF患者，应禁用达比加群，因为上市后调查中报告了一些致命出血病例。
