美国科罗拉多大学安舒兹医学院Marc P. Bonaca研究小组探讨了利伐沙班在血运重建术后外周动脉疾病中的作用。2020年3月28日，《新英格兰医学杂志》在线发表了这一成果。

进行下肢血运重建的外周动脉疾病患者发生重大不良肢体和心血管事件的风险很高。在此情况下，利伐沙班的疗效和安全性尚不确定。

在一项双盲试验中，研究组招募了6564例接受血运重建术的外周动脉疾病患者，将其随机分组，其中3286例接受利伐沙班+阿司匹林治疗，3278例接受安慰剂+阿司匹林治疗。主要疗效结局是急性肢体缺血、血管原因造成的截肢、心肌梗塞、缺血性中风或心血管死亡的综合结果。

利伐沙班组有508例患者发生主要疗效结局，安慰剂组有584例，Kaplan-Meier估计的3年发生率分别为17.3%和19.9%，风险比为0.85。利伐沙班组有62例（2.65%）患者发生心肌梗塞溶栓（TIMI）大出血，安慰剂组有44例（1.87%），风险比为1.43。利伐沙班组有140例（5.94%）患者发生了国际血栓和止血协会（ISTH）定义的大出血，安慰剂组有100例（4.06%），风险比为1.42。

总之，对于进行了下肢血运重建的外周动脉疾病患者，采用利伐沙班+阿司匹林治疗与单独阿司匹林相比可显著改善预后，但ISTH大出血的风险较高。

附：英文原文

Title: Rivaroxaban in Peripheral Artery Disease after Revascularization | NEJM

Author: Marc P. Bonaca, M.D., M.P.H.,, Rupert M. Bauersachs, M.D.,, Sonia S. Anand, M.D.,, E. Sebastian Debus, M.D., Ph.D.,, Mark R. Nehler, M.D.,, Manesh R. Patel, M.D.,, Fabrizio Fanelli, M.D.,, Warren H. Capell, M.D.,, Lihong Diao, M.D.,, Nicole Jaeger, M.S.,, Connie N. Hess, M.D., M.H.S.,, Akos F. Pap, M.Sc.,, John M. Kittelson, Ph.D.,, Ivan Gudz, M.D., Ph.D.,, Lajos Mátyás, M.D.,, Dainis K. Krievins, M.D.,, Rafael Diaz, M.D.,, Marianne Brodmann, M.D.,, Eva Muehlhofer, M.D.,, Lloyd P. Haskell, M.D.,, Scott D. Berkowitz, M.D.,, and William R. Hiatt, M.D.

Issue&Volume: 2020-03-28

Abstract: Abstract

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.

DOI: 10.1056/NEJMoa2000052

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2000052