From the Department of Neurology, Neurosurgery and Medicine (R.C.), McGill University, Montreal, Canada; Department of Biostatistics (Y.Z., L.A.M.), University of Alabama at Birmingham; Department of Medicine (Neurology) (R.G.H.), McMaster University, Hamilton, Canada; Hennepin County Medical Center (Neurology) (D.C.A.), University of Minnesota Medical School, Minneapolis; Department of Clinical Pharmacy (R.L.T.), University of Texas, Austin; and Department of Medicine (O.R.B.), Brain Research Center, University of British Columbia, Vancouver, Canada.
Neurology. 2014 Feb 4;82(5):382-9. doi: 10.1212/WNL.0000000000000076. Epub 2014 Jan 2.
To assess whether adding clopidogrel to acetylsalicylic acid (ASA) has a long-term protective vascular effect in patients with lacunar stroke while taking ASA.
Post hoc analysis of 838 patients with ASA failure and recent lacunar stroke from the Secondary Prevention of Small Subcortical Strokes Trial (SPS3) cohort randomly allocated to aspirin (325 mg/day) and clopidogrel (75 mg/day) or placebo. Primary efficacy outcome was stroke recurrence (ischemic and intracranial hemorrhage) and main safety outcome was major extracranial hemorrhage. Patients were followed for a mean period of 3.5 years.
The ASA failure group had a significantly higher risk of vascular events including ischemic stroke when compared with the non-ASA failure group (n = 2,151) in SPS3 (p = 0.03). Mean age was 65.6 years and 65% were men. The risk of recurrent stroke was not reduced in the dual antiplatelet group, 3.1% per year, compared to the aspirin-only group, 3.3% per year (hazard ratio [HR] 0.91; 95% confidence interval [CI] 0.61-1.37). There was also no difference between groups for ischemic stroke (HR 0.90; 95% CI 0.59-1.38). The risk of gastrointestinal bleeding was higher in the dual antiplatelet group (HR 2.7; 95% CI 1.1-6.9); however, the risk of intracranial hemorrhage was not different.
In patients with a recent lacunar stroke while taking ASA, the addition of clopidogrel did not result in reduction of vascular events vs continuing ASA only.
This study provides Class I evidence that for patients with recent lacunar stroke while taking ASA, adding clopidogrel as compared to continuing ASA alone does not reduce the risk of recurrent stroke.
评估在服用阿司匹林（ASA）的情况下，加用氯吡格雷对 ASA 失败的腔隙性卒中患者是否具有长期的血管保护作用。
对来自二级预防小皮质下卒中试验（SPS3）队列中 838 例 ASA 失败且近期发生腔隙性卒中的患者进行事后分析，这些患者被随机分配至阿司匹林（325mg/天）和氯吡格雷（75mg/天）或安慰剂组。主要疗效终点是卒中复发（缺血性和颅内出血），主要安全性终点是主要颅外出血。患者的平均随访时间为 3.5 年。
SPS3 中，ASA 失败组的血管事件（包括缺血性卒中和颅内出血）风险明显高于非 ASA 失败组（n=2151）（p=0.03）。平均年龄为 65.6 岁，65%为男性。与阿司匹林单药组相比，双联抗血小板组（每年 3.1%）的卒中复发风险并未降低，每年 3.3%（风险比[HR]0.91；95%置信区间[CI]0.61-1.37）。两组之间缺血性卒中也无差异（HR 0.90；95%CI 0.59-1.38）。双联抗血小板组的胃肠道出血风险更高（HR 2.7；95%CI 1.1-6.9）；然而，颅内出血风险无差异。
在服用 ASA 的近期腔隙性卒中患者中，加用氯吡格雷并未降低血管事件的风险，与继续服用 ASA 单药相比。
本研究提供了 I 级证据，表明对于正在服用 ASA 且近期发生腔隙性卒中的患者，与继续单独使用 ASA 相比，加用氯吡格雷不能降低卒中复发的风险。
