Prevention of stroke and systemic embolism with rivaroxaban compared with warfarin in patients with non-valvular atrial fibrillation and moderate renal impairment
Prevention of stroke and systemic embolism with rivaroxaban compared with warfarin in patients with non-valvular atrial fibrillation and moderate renal impairment
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DOI：
10.1093/eurheartj/ehr342
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发表时间：
2011-10-01
影响因子：
39.3
通讯作者：
Califf, Robert M.
中科院分区：
文献类型：
--
作者：
Fox, Keith A. A.;Piccini, Jonathan P.;Califf, Robert M.
非瓣膜性房颤（AF）和肾功能不全患者在抗凝治疗期间发生缺血性卒中和出血的风险增加。利伐沙班是一种口服的Xa因子直接抑制剂，主要通过肝脏代谢，方法和结果我们在一项双盲试验中将14264例AF患者随机分为利伐沙班20 mg/天[如果肌酐清除率（CrCl）30-49 mL/min，则为15 mg/天]或剂量调整的华法林组（目标国际标准化比率2.0-3.0）。与CrCl >50 mL/min的患者（平均年龄73岁）相比，2950例（20.7%）CrCl 30-49 mL/min的患者年龄更大（79岁），无论研究治疗如何，事件发生率更高。在CrCl 30-49 mL/min的受试者中，在符合方案人群中，利伐沙班15 mg/d组卒中或全身性栓塞的主要终点发生率为2.32/100患者年，华法林组为2.77/100患者年[风险比（HR）0.84; 95%置信区间（CI）0.57-1.23]。意向治疗分析得出的结果与符合方案结果相似（HR 0.86; 95% CI 0.63-1.17）。利伐沙班或华法林的主要安全性终点（严重和临床相关非严重出血：17.82 vs. 18.28/100患者-年; P = 0.76）和颅内出血（0.71 vs. 0.88/100患者-年; P = 0.54）发生率相似。利伐沙班组致死性出血发生率（0.28 vs.0.74%/100 patient-year; P = 0.047）较低。结论房颤合并中度肾功能不全患者的卒中和出血发生率高于肾功能正常者。没有证据表明各给药组的治疗效果存在异质性。与调整剂量的华法林相比，ROCKET-AF的剂量调整产生的结果与总体试验一致。
Aims Patients with non-valvular atrial fibrillation (AF) and renal insufficiency are at increased risk for ischaemic stroke and bleeding during anticoagulation. Rivaroxaban, an oral, direct factor Xa inhibitor metabolized predominantly by the liver, preserves the benefit of warfarin for stroke prevention while causing fewer intracranial and fatal haemorrhages.Methods and results We randomized 14 264 patients with AF in a double-blind trial to rivaroxaban 20 mg/day [ 15 mg/day if creatinine clearance (CrCl) 30-49 mL/min] or dose-adjusted warfarin (target international normalized ratio 2.0-3.0). Compared with patients with CrCl >50 mL/min (mean age 73 years), the 2950 (20.7%) patients with CrCl 30-49 mL/min were older (79 years) and had higher event rates irrespective of study treatment. Among those with CrCl 30-49 mL/min, the primary endpoint of stroke or systemic embolism occurred in 2.32 per 100 patient-years with rivaroxaban 15 mg/day vs. 2.77 per 100 patient-years with warfarin [hazard ratio (HR) 0.84; 95% confidence interval (CI) 0.57-1.23] in the per-protocol population. Intention-to-treat analysis yielded similar results (HR 0.86; 95% CI 0.63-1.17) to the per-protocol results. Rates of the principal safety endpoint (major and clinically relevant non-major bleeding: 17.82 vs. 18.28 per 100 patient-years; P = 0.76) and intracranial bleeding (0.71 vs. 0.88 per 100 patient-years; P = 0.54) were similar with rivaroxaban or warfarin. Fatal bleeding (0.28 vs. 0.74% per 100 patient-years; P = 0.047) occurred less often with rivaroxaban.Conclusion Patients with AF and moderate renal insufficiency have higher rates of stroke and bleeding than those with normal renal function. There was no evidence of heterogeneity in treatment effect across dosing groups. Dose adjustment in ROCKET-AF yielded results consistent with the overall trial in comparison with dose-adjusted warfarin.