From the Julius Center for Health Sciences and Primary Care (J.P.G., J.B.R., A.A.).
Department of Neurology, University Hospital Essen, Germany (H.-C.D.).
Stroke. 2019 Jul;50(7):1812-1818. doi: 10.1161/STROKEAHA.118.024497. Epub 2019 Jun 10.
Background and Purpose- We assessed the efficacy and safety of antiplatelet agents after noncardioembolic stroke or transient ischemic attack and examined how these vary according to patients' demographic and clinical characteristics. Methods- We did a network meta-analysis (NMA) of data from 6 randomized trials of the effects of commonly prescribed antiplatelet agents in the long-term (≥3 months) secondary prevention of noncardioembolic stroke or transient ischemic attack. Individual patient data from 43 112 patients were pooled and reanalyzed. Main outcomes were serious vascular events (nonfatal stroke, nonfatal myocardial infarction, or vascular death), major bleeding, and net clinical benefit (serious vascular event or major bleeding). Subgroup analyses were done according to age, sex, ethnicity, hypertension, qualifying diagnosis, type of vessel involved (large versus small vessel disease), and time from qualifying event to randomization. Results- Aspirin/dipyridamole combination (RR, 0.83; 95% CI, 0.74-0.94) significantly reduced the risk of vascular events compared with aspirin, as did clopidogrel (RR, 0.88; 95% CI, 0.78-0.98), and aspirin/clopidogrel combination (RR, 0.83; 95% CI, 0.71-0.96). Clopidogrel caused significantly less major bleeding and intracranial hemorrhage than aspirin, aspirin/dipyridamole combination, and aspirin/clopidogrel combination. Aspirin/clopidogrel combination caused significantly more major bleeding than aspirin, aspirin/dipyridamole combination, and clopidogrel. Net clinical benefit was similar for clopidogrel and aspirin/dipyridamole combination (RR, 0.99; 95% CI, 0.93-1.05). Subgroup analyses showed no heterogeneity of treatment effectiveness across prespecified subgroups. The excess risk of major bleeding associated with aspirin/clopidogrel combination compared with clopidogrel alone was higher in patients aged <65 years than it was in patients ≥65 years (RR, 3.9 versus 1.7). Conclusions- Results favor clopidogrel and aspirin/dipyridamole combination for long-term secondary prevention after noncardioembolic stroke or transient ischemic attack, regardless of patient characteristics. Aspirin/clopidogrel combination was associated with a significantly higher risk of major bleeding compared with other antiplatelet regimens.
背景和目的- 我们评估了非心源性卒中和短暂性脑缺血发作后抗血小板药物的疗效和安全性,并检查了这些药物根据患者的人口统计学和临床特征的变化情况。方法- 我们对 6 项常用抗血小板药物长期(≥3 个月)二级预防非心源性卒中和短暂性脑缺血发作的效果的随机试验进行了网络荟萃分析(NMA)。来自 43112 名患者的个体患者数据被汇总并重新分析。主要结局是严重血管事件(非致命性卒中、非致命性心肌梗死或血管性死亡)、大出血和净临床获益(严重血管事件或大出血)。亚组分析根据年龄、性别、种族、高血压、诊断类型、涉及血管类型(大血管疾病与小血管疾病)以及从确诊事件到随机分组的时间进行。结果- 与阿司匹林相比,阿司匹林/双嘧达莫联合用药(RR,0.83;95%CI,0.74-0.94)显著降低了血管事件的风险,氯吡格雷(RR,0.88;95%CI,0.78-0.98)和阿司匹林/氯吡格雷联合用药(RR,0.83;95%CI,0.71-0.96)也是如此。氯吡格雷引起的大出血和颅内出血明显少于阿司匹林、阿司匹林/双嘧达莫联合用药和阿司匹林/氯吡格雷联合用药。阿司匹林/氯吡格雷联合用药引起的大出血明显多于阿司匹林、阿司匹林/双嘧达莫联合用药和氯吡格雷。氯吡格雷和阿司匹林/双嘧达莫联合用药的净临床获益相似(RR,0.99;95%CI,0.93-1.05)。亚组分析显示,在预定的亚组中,治疗效果没有异质性。与单独使用氯吡格雷相比,阿司匹林/氯吡格雷联合用药在年龄<65 岁的患者中与大出血相关的额外风险高于年龄≥65 岁的患者(RR,3.9 比 1.7)。结论- 无论患者特征如何,结果都倾向于氯吡格雷和阿司匹林/双嘧达莫联合用药用于非心源性卒中和短暂性脑缺血发作后的长期二级预防。与其他抗血小板药物方案相比,阿司匹林/氯吡格雷联合用药与大出血风险显著增加相关。