Centre for Cardiovascular Science, University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK.
Eur Heart J. 2011 Oct;32(19):2387-94. doi: 10.1093/eurheartj/ehr342. Epub 2011 Aug 28.
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.
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.
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.
非瓣膜性心房颤动（AF）合并肾功能不全的患者发生缺血性卒中及抗凝相关出血的风险增加。利伐沙班是一种口服、直接的 Xa 因子抑制剂，主要经肝脏代谢，在预防卒中方面保留了华法林的疗效，同时颅内出血和致死性出血的发生率更低。
我们在一项双盲试验中，将 14264 例 AF 患者随机分为利伐沙班组（20mg/天，CrCl30-49ml/min 时为 15mg/天）或调整剂量的华法林组（目标国际标准化比值 2.0-3.0）。与 CrCl＞50ml/min 的患者（平均年龄 73 岁）相比，2950 例（20.7%）CrCl30-49ml/min 的患者年龄更大（79 岁），无论接受何种治疗，事件发生率均更高。在 CrCl30-49ml/min 的患者中，利伐沙班 15mg/天组和华法林组的主要终点（卒中和全身性栓塞）发生率分别为每 100 患者年 2.32 例和 2.77 例（风险比 [HR]0.84；95%置信区间 [CI]0.57-1.23），在符合方案人群中。意向治疗分析得出的结果（HR0.86；95%CI0.63-1.17）与符合方案结果相似。主要安全性终点（主要和临床相关非主要出血：17.82 与 18.28 每 100 患者年；P=0.76）和颅内出血（0.71 与 0.88 每 100 患者年；P=0.54）的发生率在利伐沙班和华法林组相似。利伐沙班组的致命性出血（0.28 与每 100 患者年 0.74%；P=0.047）发生率更低。
AF 合并中度肾功能不全的患者发生卒中和出血的风险高于肾功能正常的患者。各剂量组之间治疗效果无差异。ROCKET-AF 研究中的剂量调整与调整剂量的华法林相比，结果与总试验一致。
