Background: Patients with minor acute ischemic stroke or transient ischemic attack are at high risk for subsequent stroke, and more potent antiplatelet therapy in the acute setting is needed. However, the potential benefit of more intense antiplatelet therapy must be assessed in relation to the risk for major bleeding. The SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) was the first trial with ticagrelor in patients with acute ischemic stroke or transient ischemic attack in which the efficacy and safety of ticagrelor were compared with those of aspirin. The main safety objective was assessment of PLATO (Platelet Inhibition and Patient Outcomes)–defined major bleeds on treatment, with special focus on intracranial hemorrhage (ICrH).

Methods: An independent adjudication committee blinded to study treatment classified bleeds according to the PLATO, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definitions. The definitions of ICrH and major bleeding excluded cerebral microbleeds and asymptomatic hemorrhagic transformations of cerebral infarctions so that the definitions better discriminated important events in the acute stroke population.

Results: A total of 13 130 of 13 199 randomized patients received at least 1 dose of study drug and were included in the safety analysis set. PLATO major bleeds occurred in 31 patients (0.5%) on ticagrelor and 38 patients (0.6%) on aspirin (hazard ratio, 0.83; 95% confidence interval, 0.52–1.34). The most common locations of major bleeds were intracranial and gastrointestinal. ICrH was reported in 12 patients (0.2%) on ticagrelor and 18 patients (0.3%) on aspirin. Thirteen of all 30 ICrHs (4 on ticagrelor and 9 on aspirin) were hemorrhagic strokes, and 4 (2 in each group) were symptomatic hemorrhagic transformations of brain infarctions. The ICrHs were spontaneous in 6 and 13, traumatic in 3 and 3, and procedural in 3 and 2 patients on ticagrelor and aspirin, respectively. In total, 9 fatal bleeds occurred on ticagrelor and 4 on aspirin. The composite of ICrH or fatal bleeding included 15 patients on ticagrelor and 18 on aspirin. Independently of bleeding classification, PLATO, TIMI, or GUSTO, the relative difference between treatments for major/severe bleeds was similar. Nonmajor bleeds were more common on ticagrelor.

Conclusions: Antiplatelet therapy with ticagrelor in patients with acute ischemic stroke or transient ischemic attack showed a bleeding profile similar to that of aspirin for major bleeds. There were few ICrHs.

Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01994720.

背景：患有轻度急性缺血性中风或短暂性脑缺血发作的患者随后发生中风的风险很高，因此在急性环境中需要更有效的抗血小板治疗。但是，必须根据严重出血的风险评估更强的抗血小板治疗的潜在益处。SOCRATES试验（使用阿司匹林或Ticagrelor治疗急性中风或短暂性脑缺血发作和患者结果）是第一个使用替卡格雷治疗急性缺血性中风或短暂性脑缺血发作的患者的试验，该试验将替卡格雷的疗效和安全性与阿司匹林进行了比较。主要安全目标是评估PLATO（血小板抑制和患者预后）–定义的主要治疗出血点，特别关注颅内出血（ICrH）。

方法：一个独立的审判委员会对根据PLATO，TIMI（心肌梗死中的溶栓）和GUSTO（全球开放性冠状动脉阻塞治疗策略）的定义进行研究，以盲目地研究治疗分类的出血。ICrH和大出血的定义排除了脑梗死的脑微出血和无症状的出血性转化，因此这些定义可以更好地区分急性中风人群中的重要事件。

结果：在13 199名随机分组患者中，共有13 130名患者接受了至少1剂研究药物，并纳入了安全性分析集。接受替卡格雷治疗的31例患者（0.5％）和接受阿司匹林治疗的38例患者（0.6％）发生了PLATO大出血（危险比，0.83； 95％置信区间，0.52-1.34）。主要出血的最常见部位是颅内和胃肠道。替卡格雷治疗组有12例患者（0.2％）接受阿司匹林治疗，有18例患者（0.3％）有ICrH报道。30例ICrH中有13例（替卡格雷4例，阿司匹林9例）是出血性中风，4例（每组2例）是脑梗死的症状性出血性转变。替卡格雷和阿司匹林的ICrHs分别在6和13例中是自发的，在3和3例中是创伤性的，在3和2例中是程序性的。替卡格雷和阿司匹林总共发生9例致命出血，阿司匹林发生4例致命出血。ICrH或致命性出血的复合物包括15例替卡格雷或18例阿司匹林患者。独立于出血分类，PLATO，TIMI或GUSTO，大出血/重度出血的治疗之间的相对差异相似。非大出血在替卡格雷中较常见。

结论：替卡格雷对急性缺血性中风或短暂性脑缺血发作的患者进行抗血小板治疗，其出血特征与阿司匹林相似，可用于主要出血。ICrH很少。

临床试验注册： URL：http : //www.clinicaltrials.gov。唯一标识符：NCT01994720。