2015年1月8日，美国食品药品监督管理局(FDA)批准抗凝血药Savaysa(依度沙班[edoxaban]片)在患者有心房纤颤中减低卒中的风险和危险的血凝块(全身性栓塞)不是心瓣膜引起的问题。
心房纤颤是异常心律最常见类型之一。当心脏的两个上腔(心房)不能适当地收缩时，允许血液形成凝块时发生，凝块可能脱落和至大脑或身体其他部分。有心房纤颤患者经受一个异常，不规则和快速心跳。
Savaysa也曾早已用一种抗-凝血药通过注射或输注(非肠道地)治疗共5至10天患者被批准治疗深静脉血栓形成(DVT)和肺栓塞(PE)。
DVT是一种在身体深静脉，通常在下肢或大腿形成的血液凝块。一种潜在地致命情况被称为PE结果当在深静脉脱落和转移至肺动脉和阻断血流。
FDA的药品评价和研究中心心血管和肾产品部主任Norman Stockbridge，M.D.，Ph.D.说：“在有心房纤颤患者中，抗-凝药通过预防心脏中血凝块形成降低卒中的风险，”“对于患者重要的是有这些各种类型药物可供选择。”
在21,105例参加者的一项临床试验中研究中研究不是由心脏瓣膜病所致有心房纤颤患者Savaysa治疗的安全性和疗效。试验比较两个剂量水平的Savaysa与抗耐药华法林[warfarin]对卒中和危险的血凝块发生率的影响(全身性栓子)。试验结果显示对卒中的风险减低较高剂量Savaysa与华法林相似。  而华法林在减低有心房纤颤患者卒中的风险是高度有效，它增加出血的风险。与华法林比较Savaysa被证实显著较低出血。
在8,292例参加者中研究Savaysa对有DVT和PE患者的治疗。研究比较Savaysa与华法林对治疗患者有一个DVT和/或减低PE减低症状性静脉血栓栓塞(VTE)事件的复发率(其中包括DVT，PE，和VTE-相关死亡)的安全性和疗效。在试验中，用Savaysa参加者有症状性复发VTE 3.2%与之比较用华法林为3.5%。
在临床试验中参加者最常观察到副作用是出血和贫血。如同用其他FDA-批准的抗-凝血药，出血，包括危及生命出血，是用Savaysa最严重风险。没有治疗曾被证明逆转Savaysa的抗凝血效应。
Savaysa有一个黑框警告为卫生保健专业人员提供关于特异性患者组重要给药和安全性信息，包括一个警告in有肌酐清除率大于95 ml/min心房纤颤患者Savaysa有效较低。一个患者的肌酐水平通过测量在血液或尿中废产物肌酐水平显示正在工作患者的肾脏肌酐清除率水平。在开始用Savaysa前应评估这个。有肌酐清除率大于95 ml/min患者与给华法林相似患者比较有卒中的风险增加。Savaysa不应在非瓣膜性心房纤颤有较高肌酐清除率患者中使用。应使用另一种抗凝剂。
如同用其他抗凝剂，黑框警告忠告过早终止Savaysa增加卒中的风险和用Savaysa治疗患者中在脊柱周围正在接受被注射的麻醉剂或正在进行脊髓穿刺注意到可能发生脊髓或硬膜外血肿。
Savaysa将随提供指导其使用和药物安全性信息的患者用药指南分发。卫生保健专业人员应与患者商讨关于用这个产品出血的风险增加。
Savaysa由总部在东京的Daiichi Sankyo 有限公司制造。
edoxaban (Lixiana, Savaysa (US))
New Drugs Online Report for edoxaban
Information
Generic Name: edoxaban  
Trade Name: Lixiana, Savaysa (US) 
Synonym: DU 176b 
Entry Type: New molecular entity  
Developmental Status
UK: Pre-registration (Filed) 
EU: Pre-registration (Filed) 
US: Approved (Licensed) 
UK launch Plans: Available only to registered users
Actual UK launch date:  
Comments
Jan 15: Approved in the US to treat DVT & PE in pts who have already been treated with an anti-clotting drug for five to ten days. Savaysa also approved to reduce risk of stroke and SE in pts with AF not caused by a heart valve problem. It will be launched in the US in Feb 15 [11].
09/01/2015 11:38:25 
Jan 14: Filed in the US for the reduction in risk of stroke and systemic embolic events (SEE) in patients with non-valvular atrial fibrillationand for the treatment of DVT or PE and for the prevention of recurrence of symptomatic VTE. Savaysa is the proposed brand name for edoxaban if approved for marketing in the US [10]
10/01/2014 11:49:19 
Jan 14: Filed in the EU for treatment of DVT or pulmonary embolism and prevention of recurrence of symptomatic venous thromboembolism. Also filed for the prevention of stroke and systemic embolic events in patients with non-valvular atrial fibrillation [9]. 
08/01/2014 08:17:43 
Nov 13: Company plans to file in EU, US and Japan in Q1 2014 [7].
20/11/2013 09:32:54 
Trial or other data
Dec 13: Hokusai-VTE subgroup analysis data presented: 771 cancer patients treated with edoxaban had a numerically lower incidence of recurrent symptomatic VTE compared to warfarin (3.7% vs. 7.1%, HR 0.53, 95% CI 0.28 to 1.00). Once-daily edoxaban also had a lower incidence of clinically relevant bleeding (major or non-major) compared to warfarin in cancer patients (12.4% vs. 18.8%). [8]
10/12/2013 13:01:00
Sep 13: HOKUSAI VTE study published in NEJM. A total of 4921 patients presented with DVT & 3319 with a PE. Among patients receiving warfarin, the time in the therapeutic range was 63.5%. Edoxaban was noninferior to warfarin with respect to the primary efficacy outcome, which occurred in 130 patients in the edoxaban group (3.2%) and 146 patients in the warfarin group (3.5%) (hazard ratio, 0.89; 95% confidence interval [CI], 0.70 to 1.13; P<0.001 for noninferiority). The safety outcome occurred in 349 patients (8.5%) in the edoxaban group and 423 patients (10.3%) in the warfarin group (hazard ratio, 0.81; [0.71 to 0.94]; P=0.004 for superiority). The rates of other adverse events were similar in the two groups. A total of 938 patients with PE had right ventricular dysfunction, as assessed by measurement of N-terminal pro–brain natriuretic peptide levels; the rate of recurrent VTE in this subgroup was 3.3% in the edoxaban group and 6.2% in the warfarin group (hazard ratio, 0.52; [0.28 to 0.98]) [6].
04/09/2013 10:57:21
Apr 13: Daiichi Sankyo is supporting a PI study of PER977, an experimental drug from Perosphere designed to reverse the anticoagulant activity of edoxaban [5]
26/04/2013 14:28:25
Apr 13: Completion of the HOKUSAI VTE study now expected Mar 13 [4]. 
26/04/2013 14:24:06
Oct 12: Enrollment completed in the Hokusai-VTE study, which is the largest single phase 3 clinical study in the treatment and prevention of recurrence of VTE. More than 8,250 patients have been enrolled in the trial from more than 400 clinical sites across 38 countries worldwide.The Hokusai-VTE study has been designed to reflect clinical practice, using a standard heparin lead-in, and providing a flexible treatment duration of three, six or 12 months. Edoxaban 60mg once-daily will be compared to warfarin control therapy (target INR 2-3). This study design is allowing investigators to evaluate patients with a broad range of risks, including patients with moderate or severe conditions of PE and DVT. [3] 
26/10/2012 08:36:49
Jan 12: Completion of the HOKUSAI VTE study expected by Apr 12 [2].
01/05/2012 10:39:06
Feb 10: NCT00986154 study = HOKUSAI VTE study. Phase III, event-driven, randomised, double-blind, double-dummy, parallel-group, multi-centre, multi-national trial assessing the safety and efficacy of edoxaban in reducing recurrent venous thromboembolic (VTE) complications in patients with DVT and/or PE. The main efficacy outcome for HOKUSAI VTE is the recurrence of symptomatic VTE (i.e., the composite of DVT, non-fatal PE and fatal PE). The primary safety assessment is the incidence of major and clinically relevant non-major bleeding. 7,500 patients will be randomised to two different treatment groups. Both groups will receive open label enoxaparin or unfractionated heparin for at least five days and up to 12 days, followed by double-blind warfarin or edoxaban (60 mg once-daily). Patients will receive treatment for up to 12 months in accordance to the standard of care and international guidelines. [1] 
16/11/2011 14:39:34

Evidence Based Evaluations
NICE scope  http://www.nice.org.uk/guidance/gid-tag476/resources/deep-vein-thrombosis-pulmonary-embolism-treatment-secondary-prevention-edoxaban-tosylate-appendix-b-draft-scope-for-consultation-prereferral-march-2014-2 
NHSC  http://www.nhsc-healthhorizons.org.uk/files/downloads/1764/2177.45fbdc3b.Edoxabantosylate.pdf 
References  
Available only to registered users
Category
BNF Category: Oral anticoagulants (02.08.02)
Pharmacology: Factor Xa inhibitor  
Epidemiology: Estimates of the incidence of VTE vary. In England in 2009-10 there were just over 37,000 finished consultant episodes with a diagnosis of PE (~71 per 100,000 people). People who have had an episode of VTE have a risk of recurrence within 8 years of about 30%.  
Indication: Venous thromboembolism (VTE) 
Additional Details:  
Method(s) of Administration  
Oral 
Company Information
Name: Daiichi Sankyo 
US Name: Daiichi Sankyo 
NICE Information
Anticipated Commissioning route (England) - 
In timetable: Yes  
When: Oct / 2015 
Note: www.nice.org.uk/Guidance/InDevelopment/GID-TAG476