Pan Yuesong, Elm Jordan J, Li Hao, Easton J Donald, Wang Yilong, Farrant Mary, Meng Xia, Kim Anthony S, Zhao Xingquan, Meurer William J, Liu Liping, Dietrich Dennis, Wang Yongjun, Johnston S Claiborne
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
China National Clinical Research Center for Neurological Diseases, Beijing, China.
JAMA Neurol. 2019 Dec 1;76(12):1466-1473. doi: 10.1001/jamaneurol.2019.2531.
Dual antiplatelet therapy with clopidogrel and aspirin is effective for secondary prevention after minor ischemic stroke or transient ischemic attack (TIA). Uncertainties remained about the optimal duration of dual antiplatelet therapy for minor stroke or TIA.
To obtain precise estimates of efficacy and risk of dual antiplatelet therapy after minor ischemic stroke or TIA.
DESIGN, SETTING, AND PARTICIPANTS: This analysis pooled individual patient-level data from 2 large-scale randomized clinical trials that evaluated clopidogrel-aspirin as a treatment to prevent stroke after a minor stroke or high-risk TIA. The Clopidogrel in High-Risk Patients With Acute Non-Disabling Cerebrovascular Events (CHANCE) trial enrolled patients at 114 sites in China from October 1, 2009, to July 30, 2012. The Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial enrolled patients at 269 international sites from May 28, 2010, to December 19, 2017. Both were followed up for 90 days. Data analysis occurred from November 2018 to May 2019.
In the 2 trials, patients with minor stroke or high-risk TIA were randomized to clopidogrel-aspirin or aspirin alone within 12 hours (POINT) or 24 hours (CHANCE) of symptom onset.
The primary efficacy outcome was a major ischemic event (ischemic stroke, myocardial infarction, or death from ischemic vascular causes). The primary safety outcome was major hemorrhage.
The study enrolled 5170 patients (CHANCE) and 4881 patients (POINT). Analysis included individual data from 10 051 patients (5016 in the clopidogrel-aspirin treatment group and 5035 in the control group) with a median age of 63.2 (interquartile range, 55.0-72.9) years; 6106 patients (60.8%) were male. Clopidogrel-aspirin treatment reduced the risk of major ischemic events at 90 days compared with aspirin alone (328 of 5016 [6.5%] vs 458 of 5035 [9.1%]; hazard ratio [HR], 0.70 [95% CI, 0.61-0.81]; P < .001), mainly within the first 21 days (263 of 5016 [5.2%] vs 391 of 5035 [7.8%]; HR, 0.66 [95% CI, 0.56-0.77]; P < .001), but not from day 22 to day 90. No evidence of heterogeneity of treatment outcome across trials or prespecified subgroups was observed. Major hemorrhages were more frequent in the clopidogrel-aspirin group, but the difference was nonsignificant.
In this analysis of the POINT and CHANCE trials, the benefit of dual antiplatelet therapy appeared to be confined to the first 21 days after minor ischemic stroke or high-risk TIA.
氯吡格雷与阿司匹林联合抗血小板治疗对轻度缺血性卒中或短暂性脑缺血发作（TIA）后的二级预防有效。对于轻度卒中或TIA患者，双重抗血小板治疗的最佳持续时间仍存在不确定性。
精确评估轻度缺血性卒中或TIA后双重抗血小板治疗的疗效和风险。
设计、设置和参与者：该分析汇总了2项大型随机临床试验中个体患者层面的数据，这2项试验评估了氯吡格雷 - 阿司匹林作为预防轻度卒中或高危TIA后卒中的治疗方法。急性非致残性脑血管事件高危患者的氯吡格雷（CHANCE）试验于2009年10月1日至2012年7月30日在中国114个地点招募患者。血小板导向性抑制新发性TIA和轻度缺血性卒中（POINT）试验于2010年5月28日至2017年12月19日在269个国际地点招募患者。两项试验均随访90天。数据分析于2018年11月至2019年5月进行。
在这2项试验中，轻度卒中或高危TIA患者在症状发作后12小时内（POINT）或24小时内（CHANCE）被随机分配接受氯吡格雷 - 阿司匹林或单独使用阿司匹林治疗。
主要疗效结局是重大缺血性事件（缺血性卒中、心肌梗死或缺血性血管性死亡）。主要安全性结局是大出血。
该研究纳入了5170例患者（CHANCE）和4881例患者（POINT）。分析包括来自10051例患者的个体数据（氯吡格雷 - 阿司匹林治疗组5016例，对照组5035例），中位年龄为63.2岁（四分位间距，55.0 - 72.9岁）；6106例患者（60.8%）为男性。与单独使用阿司匹林相比，氯吡格雷 - 阿司匹林治疗在90天时降低了重大缺血性事件的风险（5016例中的328例[6.5%] vs 5035例中的458例[9.1%]；风险比[HR]，0.70[95%CI，0.61 - 0.81]；P <.001），主要在前21天内（5016例中的263例[5.2%] vs 5035例中的391例[7.8%]；HR，0.66[95%CI，0.56 - 0.77]；P <.001），但在第22天至第90天并非如此。未观察到各试验或预先指定亚组之间治疗结局的异质性证据。氯吡格雷 - 阿司匹林组大出血更常见，但差异无统计学意义。
在对POINT和CHANCE试验的这项分析中，双重抗血小板治疗的益处似乎仅限于轻度缺血性卒中或高危TIA后的前21天。
