Effects of clopidogrel added to aspirin in patients with recent lacunar stroke.
Effects of clopidogrel added to aspirin in patients with recent lacunar stroke.
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DOI：
10.1056/nejmoa1204133
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发表时间：
2012-08-30
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影响因子：
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通讯作者：
Pearce LA
中科院分区：
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作者：
SPS3 Investigators;Benavente OR;Hart RG;McClure LA;Szychowski JM;Coffey CS;Pearce LA
腔隙性梗死是一种常见的中风类型，主要由脑小血管疾病引起。抗血小板治疗对二级预防的有效性尚未确定。我们进行了一项双盲、多中心试验，涉及3020例近期有症状的腔隙性脑梗死患者，这些患者通过磁共振成像确诊。患者被随机分配每天接受75 mg氯吡格雷或安慰剂;两组患者每天接受325 mg阿司匹林。主要结局是任何复发性卒中，包括缺血性卒中和颅内出血。参与者的平均年龄为63岁，其中63%为男性。经过平均3.4年的随访，阿司匹林和氯吡格雷并没有显著降低卒中复发的风险（双重抗血小板治疗）（125例卒中;发生率，每年2.5%）与阿司匹林单药相比（138次中风，每年2.7%）（风险比，0.92; 95%可信区间[CI]，0.72 - 1.16），缺血性卒中复发的风险也是（风险比，0.82; 95% CI，0.63 - 1.09）或致残性或致死性卒中（风险比，1.06; 95% CI，0.69 - 1.64）。与阿司匹林单药治疗（56例，每年1.1%）相比，双重抗血小板治疗（105例，每年2.1%）的大出血风险几乎增加一倍（风险比，1.97; 95%CI，1.41 - 2.71; P<0.001）。在可分类的复发性缺血性卒中中，71%（133/187）为腔隙性卒中。接受双重抗血小板治疗的患者全因死亡率增加（单用阿司匹林组77例死亡，双联抗血小板治疗组113例死亡）（风险比，1.52; 95% CI，1.14 - 2.04; P = 0.004）;这种差异并不是由致死性并发症引起的（接受双重抗血小板治疗的组中9例对仅接受阿司匹林治疗的组中4例）。在近期发生腔隙性卒中的患者中，阿司匹林加用氯吡格雷并不能显著降低卒中复发的风险，但会显著增加出血和死亡的风险。（由国家神经疾病和中风研究所和其他机构资助; SPS 3 ClinicalTrials.gov编号，NCT 00059306。
Lacunar infarcts are a frequent type of stroke caused mainly by cerebral small-vessel disease. The effectiveness of antiplatelet therapy for secondary prevention has not been defined. We conducted a double-blind, multicenter trial involving 3020 patients with recent symptomatic lacunar infarcts identified by magnetic resonance imaging. Patients were randomly assigned to receive 75 mg of clopidogrel or placebo daily; patients in both groups received 325 mg of aspirin daily. The primary outcome was any recurrent stroke, including ischemic stroke and intracranial hemorrhage. The participants had a mean age of 63 years, and 63% were men. After a mean follow-up of 3.4 years, the risk of recurrent stroke was not significantly reduced with aspirin and clopidogrel (dual antiplatelet therapy) (125 strokes; rate, 2.5% per year) as compared with aspirin alone (138 strokes, 2.7% per year) (hazard ratio, 0.92; 95% confidence interval [CI], 0.72 to 1.16), nor was the risk of recurrent ischemic stroke (hazard ratio, 0.82; 95% CI, 0.63 to 1.09) or disabling or fatal stroke (hazard ratio, 1.06; 95% CI, 0.69 to 1.64). The risk of major hemorrhage was almost doubled with dual antiplatelet therapy (105 hemorrhages, 2.1% per year) as compared with aspirin alone (56, 1.1% per year) (hazard ratio, 1.97; 95% CI, 1.41 to 2.71; P<0.001). Among classifiable recurrent ischemic strokes, 71% (133 of 187) were lacunar strokes. All-cause mortality was increased among patients assigned to receive dual antiplatelet therapy (77 deaths in the group receiving aspirin alone vs. 113 in the group receiving dual antiplatelet therapy) (hazard ratio, 1.52; 95% CI, 1.14 to 2.04; P = 0.004); this difference was not accounted for by fatal hemorrhages (9 in the group receiving dual antiplatelet therapy vs. 4 in the group receiving aspirin alone). Among patients with recent lacunar strokes, the addition of clopidogrel to aspirin did not significantly reduce the risk of recurrent stroke and did significantly increase the risk of bleeding and death. (Funded by the National Institute of Neurological Disorders and Stroke and others; SPS3 ClinicalTrials.gov number, NCT00059306.)