Ezekowitz Michael D, Eikelboom John, Oldgren Jonas, Reilly Paul A, Brueckmann Martina, Kent Anthony P, Pogue Janice, Spahr Judith, Clemens Andreas, Noack Herbert, Diener Hans-Christoph, Wallentin Lars, Yusuf Salim, Connolly Stuart J
Sidney Kimmel Medical College, Thomas Jefferson University, 1999 Sproul Rd., Broomall, Philadelphia, PA, USA Lankenau Medical Center, Wynnewood, PA, USA
Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Canada.
Europace. 2016 Jul;18(7):973-8. doi: 10.1093/europace/euv312. Epub 2016 Mar 3.
The Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial allowed patients who completed the trial receiving their assigned dabigatran 150 mg (D150) or 110 mg (D110) twice a day to continue into the Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY-ABLE) trial. This permitted assessment of outcomes over a median of 4.6 and a maximum of 6.7 years, respectively.
The analysed population included only those patients who completed RE-LY on dabigatran and continued into RELY-ABLE without interruption of assigned dabigatran. Cumulative risk was expressed as Kaplan-Meier plots. Outcomes were compared using Cox proportional hazard modelling. Stroke or systemic embolization rates were 1.25 and 1.54% per year (D150 and D110, respectively); hazard ratio (HR) 0.81 [95% confidence interval (CI): 0.68-0.96] (P = 0.02). Ischaemic stroke was 1.03 (D150) and 1.29%/year (D110); HR 0.79 (95% CI: 0.66-0.95) (P = 0.01). Haemorrhagic stroke rates were 0.11 (D150) and 0.13%/year (D110); HR 0.91 (95% CI: 0.51-1.62) (P = 0.75). Rates of major haemorrhage were 3.34 (D150) and 2.76%/year (D110); HR 1.22 (95% CI: 1.08-1.37) (P = 0.0008). Intracranial haemorrhage rates were 0.32 (D150) and 0.23%/year (D110); HR 1.37 (95% CI: 0.93-2.01) (P = 0.11). Mortality was 3.43 (D150) and 3.55%/year (D110); HR 0.97 (95% CI: 0.87-1.08) (P = 0.54).
Annualized rates of all outcomes were constant with better efficacy of D150, less major bleeding with D110, and low intracerebral haemorrhage rates for both doses. There were no additional safety concerns. This is the longest continuous randomized experience of a novel anticoagulant.
长期抗凝治疗随机评估（RE-LY）试验允许完成该试验且每日两次接受指定剂量达比加群酯150毫克（D150）或110毫克（D110）治疗的患者继续参与房颤患者达比加群酯治疗的长期多中心扩展试验（RELY-ABLE）。这使得分别对中位时间4.6年、最长6.7年的结局进行评估成为可能。
分析人群仅包括那些完成达比加群酯RE-LY试验并在不间断指定达比加群酯治疗的情况下继续参与RELY-ABLE试验的患者。累积风险以Kaplan-Meier曲线表示。使用Cox比例风险模型比较结局。每年的卒中或全身性栓塞发生率分别为1.25%（D150）和1.54%（D110）；风险比（HR）为0.81[95%置信区间（CI）：0.68 - 0.96]（P = 0.02）。缺血性卒中发生率分别为每年1.03%（D150）和1.29%（D110）；HR为0.79（95%CI：0.66 - 0.95）（P = 0.01）。出血性卒中发生率分别为每年0.11%（D150）和0.13%（D110）；HR为0.91（95%CI：0.51 - 1.62）（P = 0.75）。大出血发生率分别为每年3.34%（D150）和2.76%（D110）；HR为1.22（95%CI：1.08 - 1.37）（P = 0.0008）。颅内出血发生率分别为每年0.32%（D150）和0.23%（D110）；HR为1.37（95%CI：0.93 - 2.01）（P = 0.11）。死亡率分别为每年3.43%（D150）和3.55%（D110）；HR为0.97（95%CI：0.87 - 1.08）（P = 0.54）。
所有结局指标的年化发生率保持稳定，D150疗效更佳，D110大出血较少，两种剂量的颅内出血发生率均较低。未发现其他安全问题。这是新型抗凝剂最长的连续随机试验经验。
