Importance Prior trials of dual antiplatelet therapy excluded patients with moderate ischemic stroke. These patients were included in the Acute Stroke or Transient Ischaemic Attack Treated With Ticagrelor and ASA for Prevention of Stroke and Death (THALES) trial, but results have not been reported separately, raising concerns about safety and efficacy in this subgroup. Objective To evaluate the efficacy and safety of ticagrelor plus aspirin in patients with moderate ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score of 4 to 5). Design, Setting, and Participants The THALES trial was a randomized trial conducted at 414 hospitals in 28 countries in January 2018 and December 2019. This exploratory analysis compared patients with moderate stroke (baseline NIHSS score of 4 to 5) with patients with less severe stroke (NIHSS score of 0 to 3). A total of 9983 patients with stroke were included in the present analysis, after excluding 2 patients with NIHSS scores greater than 5 and 1031 patients with transient ischemic attack. Data were analyzed from March to April 2021. Interventions Ticagrelor (180-mg loading dose on day 1 followed by 90 mg twice daily on days 2 to 30) or placebo within 24 hours after symptom onset. All patients received aspirin, 300 to 325 mg, on day 1 followed by aspirin, 75 to 100 mg, daily on days 2 to 30. Patients were observed for 30 additional days. Main Outcomes and Measures The primary outcome was time to stroke or death within 30 days. The primary safety outcome was time to severe bleeding. Results In total, 3312 patients presented with moderate stroke and 6671 presented with less severe stroke. Of those in the moderate stroke group, 1293 (39.0%) were female, and the mean (SD) age was 64.5 (10.8) years; of those in the less severe stroke group, 2518 (37.7%) were female, and the mean (SD) age was 64.8 (11.2) years. The observed primary outcome event rate in patients with moderate stroke was 7.6% (129 of 1671) for those in the ticagrelor group and 9.1% (150 of 1641) for those in the placebo group (hazard ratio, 0.84; 95% CI, 0.66-1.06); the primary outcome event rate in patients with less severe stroke was 4.7% (158 of 3359) for those in the ticagrelor group and 5.7% (190 of 3312) for those in the placebo group (hazard ratio, 0.82; 95% CI, 0.66-1.01) (P for interaction = .88). Severe bleeding occurred in 8 patients (0.5%) in the ticagrelor group and in 4 patients (0.2%) in the placebo group in those with moderate stroke compared with 16 patients (0.5%) and 3 patients (0.1%), respectively, with less severe stroke (P for interaction = .26). Conclusions and Relevance In this study, patients with a moderate ischemic stroke had consistent benefit from ticagrelor plus aspirin vs aspirin alone compared with patients with less severe ischemic stroke, with no further increase in the risk of intracranial bleeding or other severe bleeding events. Trial Registration ClinicalTrials.gov Identifier: NCT03354429.

中文翻译：

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替格瑞洛和阿司匹林在中度缺血性卒中患者中的疗效和安全性：THALES 随机临床试验的探索性分析。

重要性 先前的双重抗血小板治疗试验排除了中度缺血性卒中患者。这些患者被纳入用替格瑞洛和 ASA 治疗的急性卒中或短暂性脑缺血发作预防卒中和死亡 (THALES) 试验，但结果尚未单独报告，这引发了对该亚组安全性和有效性的担忧。目的评价替格瑞洛联合阿司匹林治疗中度缺血性脑卒中（美国国立卫生研究院卒中量表[NIHSS]评分4～5分）患者的疗效和安全性。设计、设置和参与者 THALES 试验是一项随机试验，于 2018 年 1 月和 2019 年 12 月在 28 个国家的 414 家医院进行。这项探索性分析比较了中度卒中患者（基线 NIHSS 评分为 4 至 5 分）与轻度卒中患者（NIHSS 评分为 0 至 3 分）。在排除 2 名 NIHSS 评分大于 5 的患者和 1031 名短暂性脑缺血发作的患者后，本次分析共纳入 9983 名卒中患者。数据分析时间为 2021 年 3 月至 2021 年 4 月。干预措施 替格瑞洛（第 1 天 180 毫克负荷剂量，然后第 2 至 30 天每天两次 90 毫克）或安慰剂在症状发作后 24 小时内。所有患者在第 1 天接受 300 至 325 mg 的阿司匹林，然后在第 2 至 30 天每天接受 75 至 100 mg 的阿司匹林。患者再观察 30 天。主要结果和测量 主要结果是 30 天内卒中或死亡的时间。主要安全性结果是严重出血的时间。结果 总共有 3312 名患者出现中度卒中，6671 名患者出现轻度卒中。在中度卒中组中，1293 人（39.0%）为女性，平均（SD）年龄为 64.5（10.8）岁；在不太严重的卒中组中，2518 人 (37.7%) 为女性，平均 (SD) 年龄为 64.8 (11.2) 岁。在中度卒中患者中观察到的主要结局事件发生率为 7.6%（1671 名中的 129 名），替格瑞洛组和安慰剂组分别为 9.1%（1641 名中的 150 名）（风险比，0.84；95% CI，0.66 -1.06); 替格瑞洛组患者的主要结局事件发生率为 4.7%（3359 例中的 158 例），安慰剂组为 5.7%（3312 例中的 190 例）（风险比，0.82；95% CI，0.66 -1.01)（交互作用的 P = .88）。8例患者（0. 替格瑞洛组 5% 和安慰剂组 4 例（0.2%）中度卒中患者，而轻度卒中患者分别为 16 例（0.5%）和 3 例（0.1%）（交互作用 P = .26)。结论和相关性 在本研究中，与轻度缺血性卒中患者相比，中度缺血性卒中患者从替格瑞洛联合阿司匹林与单用阿司匹林中获益一致，颅内出血或其他严重出血事件的风险没有进一步增加。试验注册 ClinicalTrials.gov 标识符：NCT03354429。与轻度缺血性卒中患者相比，中度缺血性卒中患者从替格瑞洛联合阿司匹林与单用阿司匹林中获益一致，颅内出血或其他严重出血事件的风险没有进一步增加。试验注册 ClinicalTrials.gov 标识符：NCT03354429。与轻度缺血性卒中患者相比，中度缺血性卒中患者从替格瑞洛联合阿司匹林与单用阿司匹林中获益一致，颅内出血或其他严重出血事件的风险没有进一步增加。试验注册 ClinicalTrials.gov 标识符：NCT03354429。