Lip Gregory Y H, Clemens Andreas, Noack Herbert, Ferreira Jorge, Connolly Stuart J, Yusuf Salim
Professor G. Y. H. Lip, University of Birmingham, Centre for Cardiovascular Sciences, City Hospital, Birmingham, B18 7QH, UK, Tel.: +44 121 5075080, Fax: +44 121 554 4083, E-mail:
Thromb Haemost. 2014 May 5;111(5):933-42. doi: 10.1160/TH13-09-0734. Epub 2013 Dec 11.
In the RE-LY trial dabigatran 150 mg twice daily (D150) showed significantly fewer strokes, and 110 mg (D110) significantly fewer major bleeding events (MBE) compared to well-controlled warfarin in patients with atrial fibrillation (AF). The European (EU) label currently recommends the use of D150 in AF patients who are aged < 80 years without an increased risk for bleeding (e.g. HAS-BLED score <3) and not on concomitant verapamil. In other patients, D110 is recommended. In this post-hoc analysis of the RE-LY dataset, we simulated how dabigatran (n=6,004) would compare to well-controlled warfarin (n=6,022) used according to the EU label. "EU label simulated dabigatran treatment" was associated with significant reductions in stroke and systemic embolism (hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.60-0.91), haemorrhagic stroke (HR 0.22; 95%CI 0.11-0.44), death (HR 0.86; 95%CI 0.75-0.98), and vascular death (HR 0.80; 95%CI 0.68-0.95) compared to warfarin. Dabigatran was also associated with less major bleeding (HR 0.85; 95%CI 0.73-0.98), life-threatening bleeding (HR 0.72; 95%CI 0.58-0.91), intracranial haemorrhage (HR 0.28; 95%CI 0.17-0.45), and "any bleeds" (HR 0.86; 95%CI 0.81-0.92), but not gastrointestinal major bleeding (HR 1.23; 95%CI 0.96-1.59). The net clinical benefit was significantly better for dabigatran compared to warfarin. In conclusion, this post-hoc simulation of dabigatran usage based on RE-LY trial dataset indicates that "EU label simulated dabigatran treatment" may be associated with superior efficacy and safety compared to warfarin, and are in support of the EU label and the 2012 European Society of Cardiology AF guideline recommendations. Thus, adherence to European label/guideline use results in a clinically relevant benefit for dabigatran over warfarin, for both efficacy and safety.
在RE-LY试验中，与控制良好的华法林相比，每日两次服用150毫克达比加群（D150）的房颤（AF）患者中风显著减少，而每日两次服用110毫克达比加群（D110）的患者大出血事件（MBE）显著减少。欧洲（EU）药品标签目前建议，年龄小于80岁、出血风险未增加（如HAS-BLED评分<3）且未同时服用维拉帕米的房颤患者使用D150。其他患者则建议使用D110。在对RE-LY数据集的这项事后分析中，我们模拟了达比加群（n = 6,004）与按照欧盟标签使用的控制良好的华法林（n = 6,022）相比的情况。与华法林相比，“欧盟标签模拟达比加群治疗”与中风和全身性栓塞显著减少相关（风险比[HR] 0.74；95%置信区间[CI] 0.60 - 0.91）、出血性中风（HR 0.22；95%CI 0.11 - 0.44）、死亡（HR 0.86；95%CI 0.75 - 0.98）和血管性死亡（HR 0.80；95%CI 0.68 - 0.95）。达比加群还与较少的大出血（HR 0.85；95%CI 0.73 - 0.98）、危及生命的出血（HR 0.72；95%CI 0.58 - 0.91）、颅内出血（HR 0.28；95%CI 0.17 - 0.45）和“任何出血”（HR 0.86；95%CI 0.81 - 0.92）相关，但与胃肠道大出血无关（HR 1.23；95%CI 0.96 - 1.59）。与华法林相比，达比加群的净临床获益显著更好。总之，基于RE-LY试验数据集对达比加群使用情况的这项事后模拟表明，与华法林相比，“欧盟标签模拟达比加群治疗”可能具有更高的疗效和安全性，支持欧盟药品标签及2012年欧洲心脏病学会房颤指南的建议。因此，遵循欧洲药品标签/指南使用达比加群在疗效和安全性方面均比华法林具有临床相关益处。
