Rivaroxaban in Peripheral Artery Disease after Revascularization
Rivaroxaban in Peripheral Artery Disease after Revascularization
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DOI：
10.1056/nejmoa2000052
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发表时间：
2020-05-21
影响因子：
158.5
通讯作者：
Hiatt, William R.
中科院分区：
文献类型：
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作者：
Bonaca, Marc P.;Bauersachs, Rupert M.;Hiatt, William R.
接受血运重建术的外周动脉疾病患者被随机分配接受利伐沙班（2.5 mg，每日两次）或安慰剂。所有患者均服用阿司匹林。急性肢体缺血、血管性截肢、心肌梗死、缺血性卒中或心血管死亡等主要结局在利伐沙班组发生的频率较低。背景外周动脉疾病患者接受下肢血运重建术后，发生重大肢体和心血管不良事件的风险较高。在这种情况下，利伐沙班的疗效和安全性尚不确定。方法在一项双盲试验中，接受血运重建术的外周动脉疾病患者被随机分配接受利伐沙班（2.5 mg，每日2次）加阿司匹林或安慰剂加阿司匹林。主要疗效终点是急性肢体缺血、血管原因导致的主要截肢、心肌梗死、缺血性卒中或心血管原因导致的死亡的综合结果。主要的安全结局是大出血，根据心肌梗死溶栓（TIMI）分类来定义；根据国际血栓和止血学会（ISTH）的定义，大出血是次要安全结局。结果共6564例患者接受了随机分组；3286人被分配到利伐沙班组，3278人被分配到安慰剂组。利伐沙班组508例患者和安慰剂组584例患者出现主要疗效结局；Kaplan-Meier估计3年的发病率分别为17.3%和19.9%（风险比0.85,95%可信区间[CI]， 0.76 ~ 0.96； P=0.009）。利伐沙班组62例患者发生TIMI大出血，安慰剂组44例患者发生TIMI大出血（2.65%和1.87%；风险比为1.43；95% CI为0.97 ~ 2.10；P=0.07）。利伐沙班组有140例患者发生ISTH大出血，安慰剂组为100例（5.94%和4.06%；风险比为1.42；95% CI为1.10 ~ 1.84；P=0.007）。结论：在接受下肢血运重建术的外周动脉疾病患者中，利伐沙班剂量为2.5 mg，每日2次，加用阿司匹林与急性肢体缺血、血管原因的主要截肢、心肌梗死、缺血性卒中或心血管原因的死亡等综合结局的发生率显著低于单独使用阿司匹林。两组间TIMI大出血发生率无显著差异。利伐沙班和阿司匹林联合使用ISTH大出血的发生率明显高于单独使用阿司匹林。
Patients with peripheral artery disease who underwent revascularization were randomly assigned to receive rivaroxaban (2.5 mg twice daily) or placebo. All patients received aspirin. The primary outcome of acute limb ischemia, major amputation for vascular causes, MI, ischemic stroke, or cardiovascular death occurred less frequently with rivaroxaban.Background Patients with peripheral artery disease who have undergone lower-extremity revascularization are at high risk for major adverse limb and cardiovascular events. The efficacy and safety of rivaroxaban in this context are uncertain.Methods In a double-blind trial, patients with peripheral artery disease who had undergone revascularization were randomly assigned to receive rivaroxaban (2.5 mg twice daily) plus aspirin or placebo plus aspirin. The primary efficacy outcome was a composite of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from cardiovascular causes. The principal safety outcome was major bleeding, defined according to the Thrombolysis in Myocardial Infarction (TIMI) classification; major bleeding as defined by the International Society on Thrombosis and Haemostasis (ISTH) was a secondary safety outcome.Results A total of 6564 patients underwent randomization; 3286 were assigned to the rivaroxaban group, and 3278 were assigned to the placebo group. The primary efficacy outcome occurred in 508 patients in the rivaroxaban group and in 584 in the placebo group; the Kaplan-Meier estimates of the incidence at 3 years were 17.3% and 19.9%, respectively (hazard ratio, 0.85, 95% confidence interval [CI], 0.76 to 0.96; P=0.009). TIMI major bleeding occurred in 62 patients in the rivaroxaban group and in 44 patients in the placebo group (2.65% and 1.87%; hazard ratio, 1.43; 95% CI, 0.97 to 2.10; P=0.07). ISTH major bleeding occurred in 140 patients in the rivaroxaban group, as compared with 100 patients in the placebo group (5.94% and 4.06%; hazard ratio, 1.42; 95% CI, 1.10 to 1.84; P=0.007).Conclusions In patients with peripheral artery disease who had undergone lower-extremity revascularization, rivaroxaban at a dose of 2.5 mg twice daily plus aspirin was associated with a significantly lower incidence of the composite outcome of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from cardiovascular causes than aspirin alone. The incidence of TIMI major bleeding did not differ significantly between the groups. The incidence of ISTH major bleeding was significantly higher with rivaroxaban and aspirin than with aspirin alone.