达比加群酯与华法林在伴有基线肾功能异常的房颤患者中的疗效和安全性比较：RE-LY（随机评估长期抗凝治疗）试验分析。
Efficacy and safety of dabigatran compared with warfarin in relation to baseline renal function in patients with atrial fibrillation: a RE-LY (Randomized Evaluation of Long-term Anticoagulation Therapy) trial analysis.
机构信息
From Uppsala Clinical Research Center (Z.H., J.O., U.A., A.S., L.W.), Department of Medical Sciences, Cardiology (Z.H., J.O., L.W.), and Department of Medical Sciences, Clinical Chemistry (A.S.), Uppsala University, Sweden; Department of Cardiology, J.W. Goethe University, Frankfurt, Germany (S.H.H.); Population Health Research Institute, Hamilton, Ontario, Canada (S.J.C., J.W.E., S.Y.); Thomas Jefferson Medical College and the Heart Center, Wynnewood, PA (M.D.E.); and Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT (P.A.R.).
出版信息
Circulation. 2014 Mar 4;129(9):961-70. doi: 10.1161/CIRCULATIONAHA.113.003628. Epub 2013 Dec 9.
BACKGROUND
Renal impairment increases the risk of stroke and bleeding in patients with atrial fibrillation. In the Randomized Evaluation of Long-Term Anticoagulant Therapy (RELY) trial, dabigatran, with ≈80% renal elimination, displayed superiority over warfarin for prevention of stroke and systemic embolism in the 150-mg dose and significantly less major bleeding in the 110-mg dose in 18 113 patients with nonvalvular atrial fibrillation. This prespecified study investigated these outcomes in relation to renal function.
METHODS AND RESULTS
Glomerular filtration rate was estimated with the Cockcroft-Gault, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Modification of Diet in Renal Disease (MDRD) equations in all randomized patients with available creatinine at baseline (n=17 951), and cystatin C-based glomerular filtration rate was estimated in a subpopulation with measurements available (n=6190). A glomerular filtration rate ≥80, 50 to <80, and <50 mL/min was estimated in 32.6%, 47.6%, and 19.8% and in 21.6%, 59.6%, and 18.8% of patients based on Cockcroft-Gault and CKD-EPI, respectively. Rates of stroke or systemic embolism, major bleeding, and all-cause mortality increased as renal function decreased. The rates of stroke or systemic embolism were lower with dabigatran 150 mg and similar with 110 mg twice daily compared with warfarin, without significant heterogeneity in subgroups defined by renal function (interaction P>0.1 for all). For the outcome of major bleeding, there were significant interactions between treatment and renal function according to CKD-EPI and MDRD equations, respectively (P<0.05). The relative reduction in major bleeding with either dabigatran dose compared with warfarin was greater in patients with glomerular filtration rate ≥80 mL/min.
CONCLUSIONS
The efficacy of both dosages of dabigatran was consistent with the overall trial irrespective of renal function. However, with the CKD-EPI and MDRD equations, both dabigatran dosages displayed significantly lower rates of major bleeding in patients with glomerular filtration rate ≥80 mL/min.
CLINICAL TRIAL REGISTRATION URL
http://www.clinicaltrials.gov. Unique identifier: NCT00262600.
背景
肾功能损害会增加房颤患者发生卒中及出血的风险。在随机评估长期抗凝治疗（RELY）试验中，达比加群酯，约 80%经肾脏清除，与华法林相比，在预防 150mg 剂量的卒中和全身性栓塞方面具有优势，在预防 110mg 剂量的主要出血方面也具有优势，而非瓣膜性房颤患者 18113 例。本预先设定的研究调查了与肾功能相关的这些结局。
方法和结果
所有基线时肌酐值可测的随机患者（n=17951）应用 Cockcroft-Gault、慢性肾脏病流行病学合作（CKD-EPI）及改良肾脏病膳食研究（MDRD）方程估算肾小球滤过率（GFR），并在亚组中应用半胱氨酸蛋白酶抑制剂 C 估算肾小球滤过率（n=6190）。根据 Cockcroft-Gault 和 CKD-EPI 方程，估计肾小球滤过率（GFR）≥80、50~<80、<50ml/min 的患者分别占 32.6%、47.6%和 19.8%和 21.6%、59.6%和 18.8%。随着肾功能下降，卒中或全身性栓塞、大出血及全因死亡率增加。与华法林相比，达比加群酯 150mg 及 110mg 每日 2 次的卒中或全身性栓塞发生率更低，肾功能亚组间无显著异质性（根据肾功能定义的所有交互 P>0.1）。对于大出血的结局，根据 CKD-EPI 和 MDRD 方程，治疗与肾功能之间存在显著交互作用（P<0.05）。与华法林相比，达比加群酯两种剂量的大出血相对减少在肾小球滤过率≥80ml/min 的患者中更大。
结论
两种剂量的达比加群酯的疗效与总体试验一致，与肾功能无关。然而，根据 CKD-EPI 和 MDRD 方程，两种剂量的达比加群酯在肾小球滤过率≥80ml/min 的患者中显示出显著更低的大出血发生率。
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