SECONDARY PREVENTION OF SMALL SUBCORTICAL STROKES (SPSS)

整体目标 皮质下小卒中二级预防(SPS3)项目的目的是 明确预防中风复发和认知功能减退的有效治疗方法 皮质下卒中(S3)(又名腔隙性脑梗塞)。美国近200万S3病毒幸存者面临感染高危疾病 复发性中风和发展为血管性痴呆。此外，“无症状”(更准确地说是 “亚临床”)S3存在于约20%的65岁以上人群中。而S3可由多种类型的 脑血管疾病，大多是由于颅内小动脉病变引起的。最佳抗血小板药物 S3患者减少卒中复发和认知功能减退的治疗和降压管理 还没有定义，可能会产生重要的健康益处。尽管MRI定义的症状性S3在 无手术治疗的颈动脉狭窄和主要危险的心源性栓塞源是指标。 SPS3的参与事件和复发性中风是主要结果，SPS3的目标在 范围，包括评估和预防血管性痴呆。以前的临床试验都没有涉及 这些重要问题特别适用于S3患者。SPS3将定义最佳治疗以防止复发 没有动脉内膜切除术或抗凝指征的S3患者的中风和认知能力下降。 S3在西班牙裔中尤其常见，他们是最常见的中风亚型之一。 S3的预后和积极控制血压和增强血压的益处 抗血小板治疗在拉美裔有很大不同也是未知的，而这些问题将 由SPS3解决。 SPS3试图通过两个同步的方法有效解决几个重要的临床和科学问题 临床试验结合对可能影响预后的特征进行仔细的前瞻性分析 对干预措施的反应。由于高血压是中三年级最普遍和最强大的危险因素，以及 抗血小板治疗的标准是二级预防，定义疗效和安全性 血压控制和抗血小板治疗应该最好一起测试。 特定目的：明确预防中风复发和认知障碍的有效治疗方法 在有症状的S3患者中。SPS3的核心是两个涉及2500人的随机临床试验 患有症状性S3的参与者按析因设计随机分为两组。 主要目标： A)确定由阿司匹林(325 mg/d)和氯吡格雷组成的联合抗血小板治疗 在减少中风复发(主要终点)方面(75毫克/天)优于阿司匹林(325毫克/天)，认知 下降和重大血管事件。 B)确定“密集”降至特定目标范围的血压是否优于“平时” 高血压治疗可减少再发中风、认知功能衰退和主要血管事件。 次要目标： 比较联合抗血小板治疗与阿司匹林和阿司匹林的绝对益处的差异 西班牙裔参与者与非西班牙裔参与者之间的“密集”降压与“通常控制” 白人参与者。 理据‘。拉美裔美国人将从联合抗血小板药物中获得更大的好处(绝对风险降低) 与非西班牙裔相比，强化控制血压在预防中风复发方面的作用更强 白人，基于他们较高的中风复发率。 此外，将20%的西班牙裔参与者包括在内将有助于描述这一人群中的S3， 包括中风复发率和危险因素，认知下降的比率和危险因素，对 抗血小板干预和对血压控制干预的反应。 战略规划编制3的重要性/相关性。美国每年至少发生200,000起S3事件，其中近两起 数百万中三幸存者中风复发和血管性痴呆症高危人群。目前尚不清楚如何以最佳方式 预防中风复发和S3幸存者的认知障碍。目前还没有临床试验专门针对 在这个重要的、常见的笔划子类型上。没有二级中风预防研究测试过不同的靶点 卒中幸存者的血压控制水平，尽管高血压是最重要的 中风的共同独立危险因素，特别是对S3。以往的中风研究都没有集中在 西班牙裔；S3是这一增长最快的美国少数民族中最常见的中风亚型之一。其他内容 数百万美国人患有与大脑小动脉相关的“亚临床”S3和认知障碍 疾病；SPS3的结果可能也会影响他们的管理。

OVERALL AIM The aim of the Secondary Prevention of Small Subcortical Strokes (SPS3) project is to define efficacious therapies for prevention of recurrent stroke and cognitive decline in patients with small subcortical strokes (S3) (a.k.a. lacunar infarcts). Nearly two million survivors of S3 in U.S. are at high risk for recurrent stroke and for developing vascular dementia. Additionally, "asymptomatic" (more accurately termed "subclinical") S3 are present in about 20% of people over age 65. While S3 can be caused by many types of cerebrovascular disorders, most are due to intracranial cerebral small artery disease. Optimal antiplatelet therapy and antihypertensive management of S3 patients to reduce stroke recurrence and cognitive decline has not been defined and is likely to yield important health benefits. Although MRI-defined symptomatic S3 in the absence of surgically amenable cervical carotid stenosis and major-risk cardioembolic sources is the index event for participation in SPS3 and recurrent stroke is the primary outcome, the goals of SPS3 are broader in scope and include assessment and prevention of vascular dementia. No previous clinical trials have addressed these important issues specifically in S3 patients. SPS3 will define optimal treatment to prevent recurrent stroke and cognitive decline for S3 patients without an indication for endarterectomy or anticoagulation. S3s are particularly frequent in Hispanics, in whom they are one of the most common stroke subtypes. Whether the prognosis of S3 and the benefits of aggressive blood pressure control and of enhanced antiplatelet therapy are importantly different in Hispanic are also not known, and these issues will be addressed by SPS3. SPS3 seeks to efficiently address several important clinical and scientific questions through two simultaneous clinical trials coupled with careful, prospective analysis of features potentially influencing prognosis and response to interventions. Since hypertension is the most prevalent and powerful risk factor for S3, and antiplatelet therapy is the standard of care for secondary prevention, definition of the efficacy and safety of blood pressure control and antiplatelet therapy should optimally be tested together. SPECIFIC AIM: To define efficacious therapies for prevention of stroke recurrence and cognitive de-cline in patients with symptomatic S3. The core of SPS3 consists of two randomized clinical trials involving 2500 participants with symptomatic S3 randomized to two interventions in a factorial design. Primary Aims: A) To determine whether combination antiplatelet therapy consisting of aspirin (325 mg/d) plus clopidogrel (75 mg/d) is superior to aspirin (325 mg/d) for reducing stroke recurrence (the primary endpoint), cognitive decline and major vascular events. B) To determine whether "intensive" blood pressure lowering to a specific target range is superior to "usual" hypertension management for reducing recurrent stroke, cognitive decline and major vascular events. Secondary Aim: To compare the differences in absolute benefit of combination antiplatelet therapy vs. aspirin and of "intensive" blood pressure lowering vs. "usual control" between Hispanic participants vs. non-Hispanic white participants. Rationale'. Hispanics will have larger benefits (absolute risk reductions) from combination antiplatelet therapy and from "intensive" blood pressure control for prevention of stroke recurrence than non-Hispanic whites, based on their higher rate of recurrent stroke. In addition, the inclusion of 20% of Hispanic participants will serve to characterize S3 in this population, including stroke recurrence rate and risk factors, rate and risk factors for cognitive decline, response to antiplatelet intervention, and response to blood pressure control intervention. IMPORTANCE/RELEVANCE OF SPS3. At least 200,000 S3s occur annually in the U.S., with nearly two million S3 survivors at high risk for recurrent stroke and vascular dementia. It remains unclear how to optimally prevent stroke recurrence and cognitive impairment in S3 survivors. No clinical trials have specifically focused on this important, common stroke subtype. No secondary stroke prevention study has tested different target levels of blood pressure control in stroke survivors, despite the importance of hypertension as the most common independent risk factor for stroke, and particularly for S3. No previous stroke study has focused on Hispanics; S3 is one the most frequent stroke subtype among this fastest growing U.S. minority. Additional millions of Americans have "subclinical" S3 and cognitive impairment associated with cerebral small artery disease; the results of SPS3 will likely impact their management as well.