Data Coordination Unit, Department of Public Health Sciences, Medical University of South Carolina, Charleston.
Dean's Office, Dell Medical School, University of Texas at Austin, Austin.
JAMA Neurol. 2019 Jul 1;76(7):774-782. doi: 10.1001/jamaneurol.2019.0932.
Results show the short-term risk of hemorrhage in treating patients with acute transient ischemic attack (TIA) or minor acute ischemic stroke (AIS) with clopidogrel plus aspirin or aspirin alone.
To characterize the frequency and kinds of major hemorrhages in the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial.
DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of the POINT randomized, double-blind clinical trial conducted in 10 countries in North America, Europe, and Australasia included patients with high-risk TIA or minor AIS who were randomized within 12 hours of symptom onset and followed up for 90 days. The total enrollment, which occurred from May 28, 2010, through December 17, 2017, was 4881 and constituted the intention-to-treat group; 4819 (98.7%) were included in the as-treated analysis group. The primary safety analyses were as-treated, classifying patients based on study drug actually received. Intention-to-treat analyses were performed as secondary analyses. Data were analyzed in April 2018.
Patients were assigned to receive clopidogrel (600 mg loading dose on day 1 followed by 75 mg daily for days 2-90) or placebo; all patients also received open-label aspirin, 50 to 325 mg/d.
The primary safety outcome was all major hemorrhages. Other safety outcomes included minor hemorrhages.
A total of 269 sites worldwide randomized 4881 patients (median age, 65.0 years [interquartile range, 55-74 years]; 2195 women [45.0%]); the primary results have been published previously. In the as-treated analyses, major hemorrhage occurred in 21 patients (0.9%) receiving clopidogrel plus aspirin and 6 (0.2%) in the aspirin alone group (hazard ratio, 3.57; 95% CI, 1.44-8.85; P = .003; number needed to harm, 159). There were 4 fatal hemorrhages (0.1%; 3 in the clopidogrel plus aspirin group and 1 in the aspirin alone group); 3 of the 4 were intracranial. There were 7 intracranial hemorrhages (0.1%); 5 were in the clopidogrel plus aspirin group and 2 in the aspirin plus placebo group. The most common location of major hemorrhages was in the gastrointestinal tract.
The risk for major hemorrhages in patients receiving either clopidogrel plus aspirin or aspirin alone after TIA or minor AIS was low. Nevertheless, treatment with clopidogrel plus aspirin increased the risk of major hemorrhages over aspirin alone from 0.2% to 0.9%.
ClinicalTrials.gov identifier: NCT00991029.
研究结果显示，氯吡格雷联合阿司匹林或阿司匹林单药治疗急性短暂性脑缺血发作（TIA）或小面积急性缺血性脑卒中（AIS）患者的短期出血风险。
分析血小板定向抑制在新 TIA 和小面积缺血性中风（POINT）试验中主要出血的频率和类型。
设计、环境和参与者：本研究为多中心、随机、双盲临床试验的二次分析，纳入了发病 12 小时内的高危 TIA 或小面积 AIS 患者，共 4881 例患者随机分为氯吡格雷+阿司匹林组和阿司匹林单药组，随访 90 天。总入组时间为 2010 年 5 月 28 日至 2017 年 12 月 17 日，意向治疗组共 4881 例，实际接受治疗组共 4819 例（98.7%）。主要安全性分析采用按实际接受药物分类的治疗意向分析，次要安全性分析采用意向治疗分析。数据于 2018 年 4 月进行分析。
患者被随机分配接受氯吡格雷（第 1 天 600 mg 负荷剂量，第 2-90 天每天 75 mg）或安慰剂；所有患者均接受开放性阿司匹林治疗，剂量为 50-325 mg/d。
主要安全性结局为所有主要出血事件。其他安全性结局包括轻微出血事件。
全球 269 个试验点共纳入 4881 例患者（中位年龄 65.0 岁[四分位间距 55-74 岁]；2195 例女性[45.0%]）；主要结果已发表。在实际接受治疗的患者中，氯吡格雷+阿司匹林组发生 21 例（0.9%）主要出血事件，阿司匹林组发生 6 例（0.2%）（危险比，3.57；95%置信区间，1.44-8.85；P=0.003；需要治疗的人数，159）。有 4 例死亡性出血（0.1%；氯吡格雷+阿司匹林组 3 例，阿司匹林组 1 例）；其中 3 例为颅内出血。颅内出血 7 例（0.1%）；氯吡格雷+阿司匹林组 5 例，阿司匹林+安慰剂组 2 例。最常见的主要出血部位为胃肠道。
TIA 或小面积 AIS 患者接受氯吡格雷+阿司匹林或阿司匹林单药治疗后发生大出血的风险较低。然而，与阿司匹林单药治疗相比，氯吡格雷+阿司匹林治疗使大出血风险从 0.2%增加到 0.9%。
ClinicalTrials.gov 标识符：NCT00991029。
