Fordyce Christopher B, Hellkamp Anne S, Lokhnygina Yuliya, Lindner Samuel M, Piccini Jonathan P, Becker Richard C, Berkowitz Scott D, Breithardt Günter, Fox Keith A A, Mahaffey Kenneth W, Nessel Christopher C, Singer Daniel E, Patel Manesh R
From Duke Clinical Research Institute, Durham, NC (C.B.F., A.S.H., Y.L., S.M.L., J.P.P., M.R.P.); University of Cincinnati College of Medicine, OH (R.C.B.); Bayer HealthCare Pharmaceuticals, Whippany, NJ (S.D.B); Department of Cardiovascular Medicine, Division of Electrophysiology, University Hospital Münster, Germany (G.B.); Centre for Cardiovascular Science, University of Edinburgh and Royal Infirmary of Edinburgh, UK (K.A.A.F.); Department of Medicine, Stanford University, CA (K.W.M.); Janssen Research and Development, Raritan, NJ (C.C.N.); and Massachusetts General Hospital and Harvard Medical School, Boston (D.E.S.).
Circulation. 2016 Jul 5;134(1):37-47. doi: 10.1161/CIRCULATIONAHA.116.021890.
Despite rapid clinical adoption of novel anticoagulants, it is unknown whether outcomes differ among patients with worsening renal function (WRF) taking these new drugs compared with warfarin. We aimed to determine whether the primary efficacy (stroke or systemic embolism) and safety (major bleeding and nonmajor clinically relevant bleeding) end points from the ROCKET AF trial (Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation trial) differed among participants with WRF taking rivaroxaban and those taking warfarin.
After excluding patients without at least 1 follow-up creatinine measurement (n=1624), we included all remaining patients (n=12 612) randomly assigned to either rivaroxaban or dose-adjusted warfarin. On-treatment WRF (a decrease of >20% from screening creatinine clearance measurement at any time point during the study) was evaluated as a time-dependent covariate in Cox proportional hazards models.
Baseline characteristics were generally similar between patients with stable renal function (n=9292) and WRF (n=3320). Rates of stroke or systemic embolism, myocardial infarction, and bleeding were also similar, but WRF patients experienced a higher incidence of vascular death versus stable renal function (2.21 versus 1.41 events per 100 patient-years; P=0.026). WRF patients who were randomized to receive rivaroxaban had a reduction in stroke or systemic embolism compared with those taking warfarin (1.54 versus 3.25 events per 100 patient-years) that was not seen in patients with stable renal function who were randomized to receive rivaroxaban (P=0.050 for interaction). There was no difference in major or nonmajor clinically relevant bleeding among WRF patients randomized to warfarin versus rivaroxaban.
Among patients with on-treatment WRF, rivaroxaban was associated with lower rates of stroke and systemic embolism compared with warfarin, without an increase in the composite bleeding end point.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00403767.
尽管新型抗凝剂在临床上迅速得到应用，但与华法林相比，肾功能恶化（WRF）患者服用这些新药的疗效是否存在差异尚不清楚。我们旨在确定ROCKET AF试验（利伐沙班每日一次口服直接Xa因子抑制与维生素K拮抗剂预防房颤患者卒中及栓塞试验）中的主要疗效（卒中或全身性栓塞）和安全性（大出血和非大出血的临床相关出血）终点在服用利伐沙班的WRF参与者与服用华法林的参与者之间是否存在差异。
排除没有至少1次随访肌酐测量值的患者（n = 1624）后，我们纳入了所有其余随机分配至利伐沙班或剂量调整华法林的患者（n = 12612）。治疗期间的WRF（研究期间任何时间点的肌酐清除率较筛查时下降>20%）在Cox比例风险模型中作为时间依赖性协变量进行评估。
肾功能稳定的患者（n = 9292）和WRF患者（n = 3320）的基线特征总体相似。卒中或全身性栓塞、心肌梗死和出血的发生率也相似，但与肾功能稳定的患者相比，WRF患者的血管性死亡发生率更高（每100患者年2.21次事件对1.41次事件；P = 0.026）。随机接受利伐沙班的WRF患者与服用华法林的患者相比，卒中或全身性栓塞有所减少（每100患者年1.54次事件对3.25次事件），而随机接受利伐沙班的肾功能稳定患者中未观察到这种情况（交互作用P = 0.050）。随机接受华法林与利伐沙班的WRF患者在大出血或非大出血的临床相关出血方面没有差异。
在治疗期间发生WRF的患者中，与华法林相比，利伐沙班与较低的卒中和全身性栓塞发生率相关，且复合出血终点未增加。
