【Circulation】出血可增加外周血管疾病患者缺血事件的风险

我们都知道，在冠心病或脑血管疾病患者中，出血事件的发生总是与缺血事件相关。而在外周血管疾病患者都是缺血事件的高危人群，因此通常都需要接受抗栓药物治疗。那对于外周血管疾病患者而言，是否出血也会增加缺血事件的风险呢？近期发表在《循环》杂志(Circulation. 2009;120:1569-1576.)上的一项来自荷兰的BOA研究(Bypass and Oral Anticoagulants or Aspirin，旁路手术口服抗凝剂与阿司匹林对照研究)给出了答案。

该研究是一项针对腹股沟以下血管旁路手术患者口服抗凝药与阿司匹林对比的多中心、随机对照研究。主要终点事件包括非致死性心梗、非致死性缺血性卒中、大血管切断术及心血管死亡。为了判断主要出血事件能否作为缺血性事件的独立预测因子，研究通过建立多因素COX回归模型计算了原始及校正的危害比及其95%可信区间。从1995年至1998年，入选的2650位患者中共有101起非致死性的主要出血事件，经过平均14个月的随访218位患者出现主要终点事件，其中22起事件前发生主要出血事件。由出血事件到主要终点事件发生的平均时间为4个月。统计结果表明，主要出血事件会增加3倍缺血事件发生的风险。

因此作者认为，对于外周血管疾病患者而言，主要出血事件与主要缺血事件独立相关。如不考虑抗栓药物带来的获益，对于由这些出血事件所带来的风险应该引起我们足够的重视。

原文链接： http://circ.ahajournals.org/cgi/content/short/120/16/1569?rss=1

Title—
Bleeding Increases the Risk of Ischemic Events in Patients With Peripheral Arterial Disease

Background—
Patients with peripheral arterial disease are at high risk of ischemic events and therefore are treated with antithrombotics. In patients with coronary artery disease or cerebrovascular disease, bleeding is related to the subsequent occurrence of ischemic events. Our objective was to assess whether this is also the case in patients with peripheral arterial disease.

Methods and Results—
All patients from the Dutch Bypass and Oral Anticoagulants or Aspirin (BOA) Study, a multicenter randomized trial comparing oral anticoagulants with aspirin after infrainguinal bypass surgery, were included. The primary outcome event was the composite of nonfatal myocardial infarction, nonfatal ischemic stroke, major amputation, and cardiovascular death. To identify major bleeding as an independent predictor for ischemic events, crude and adjusted hazard ratios with 95% confidence intervals were calculated with multivariable Cox regression models. From 1995 until 1998, 2650 patients were included with 101 nonfatal major bleedings. During a mean follow-up of 14 months, the primary outcome event occurred in 218 patients; 22 events were preceded by a major bleeding. The mean time between major bleeding and the primary outcome event was 4 months. Major bleeding was associated with a 3-fold increased risk of subsequent ischemic events (crude hazard ratio, 3.0; 95% confidence interval, 1.9 to 4.6; adjusted hazard ratio, 3.0; 95% confidence interval, 1.9 to 4.7).

Conclusions—
In patients with peripheral arterial disease, as in patients with coronary artery disease or cerebrovascular disease, major bleeding was independently associated with major ischemic complications. Without compromising the benefits of antithrombotics, these findings call for caution relative to the risks of major bleeding.