SECONDARY PREVENTION OF SMALL SUBCORTICAL STROKES (SPS3)

小型皮质下中风（S3）是一种重要的中风亚型，约占所有缺血性中风的25%。在西班牙裔美国人中，S3是最常见的中风亚型，并且发生在相对年轻的年龄。S3通常是由于脑小动脉疾病，血管性痴呆的常见底物。超过200万的S3幸存者处于复发性中风和血管性痴呆的高风险中;还有数百万人患有亚临床S3和认知能力下降， 脑小动脉疾病小型皮质下卒中的二级预防（SPS 3）由两项随机、多中心临床试验组成，这些试验遵循NINDS申办的为期3年的初步研究。它将在35个临床试验机构招募2500名有症状的、MRI定义的3美元的受试者（其中20%为西班牙裔美国人），这些受试者没有颈动脉狭窄或主要心脏源栓塞。在析因设计中，将患者分配至两种干预措施： 1.抗血小板干预325 mg/d vs阿司匹林325 mg/d+氯吡格雷75 mg/d。 2.血压干预：收缩压目标为130至149 mmHg vs <130 mmHg。 抗血小板比较将是双盲的，而血压干预将是开放标签的，对认知和临床事件进行盲态评估和验证。每3个月随访一次，平均随访3年。 主要成果是： 1.复发性卒中（缺血性和出血性） 2.认知能力下降 3.主要血管事件 主要假设是：1。联合抗血小板治疗在预防卒中复发和减少认知功能下降方面比单独使用阿司匹林更有效。2.强化血压控制与更少的复发性中风和减少认知能力下降有关。 3.与非西班牙裔白色受试者相比，西班牙裔美国人联合抗血小板治疗和（单独）强化降压治疗对卒中和认知能力下降的绝对降低更大。以前没有随机试验专门关注S3后的二级预防，卒中后血压控制的最佳目标水平及其与认知能力下降的关系，或预防卒中和痴呆， 西班牙裔美国人SPS 3的结果可能会导致数百万S3患者严重神经系统疾病（中风和血管性痴呆）的负担显著减轻，特别是西班牙裔美国人。

Small subcortical strokes (S3) are an important stroke subtype that account for about 25% of all ischemic strokes. In Hispanic Americans, S3 are the most frequent stroke subtype and occur at a relatively young age. S3 are usually due to cerebral small artery disease, a common substrate for vascular dementia. Over two million survivors of S3 are at high risk for recurrent stroke and for vascular dementia; millions more suffer subclinical S3 and cognitive decline caused by cerebral small artery disease. Secondary Prevention of Small Subcortical Strokes (SPS3) consists of two randomized, multicenter clinical trials that follow a 3 year NINDS-sponsored pilot study. It will enroll 2500 participants (20% of whom will be Hispanic Americans) with symptomatic, MRI-defined $3 without carotid stenosis or major cardiac sources of embolism at 35 clinical sites. Patients will be assigned, in a factorial design, to two interventions: 1. Antiplatelet Intervention 325 mg/d vs aspirin 325 mg/d plus clopidogrel 75 mg/d. 2. Blood Pressure Intervention: systolic blood pressure targets of 130 to 149 mmHg vs <130 mmHg. The antiplatelet comparison will be double-blinded, while the blood pressure intervention will open-label with blinded assessment and verification of cognition and clinical events. Follow-up will be every three months for a mean of 3 years. Main outcomes are: 1. recurrent stroke (ischemic and hemorrhagic) 2. cognitive decline 3. major vascular events Key hypotheses are: 1. Combination antiplatelet therapy is more efficacious than aspirin alone for prevention of stroke recurrence and for reduction in cognitive decline. 2. Intensive blood pressure control is associated with fewer recurrent strokes and reduction in cognitive decline. 3. The absolute reduction in stroke and cognitive decline by combined antiplatelet therapy and (separately) by intensive blood pressure lowering is greater for Hispanic Americans vs. non Hispanic white participants. No previous randomized trials have focused specifically on secondary prevention after S3, on optimal target levels of blood pressure control after stroke and their relationship to cognitive decline, or on prevention of stroke and dementia in Hispanic Americans. The results of SPS3 will likely lead to important reduction in the burden of serious neurological disease (stroke and vascular dementia) for millions of people with S3, and particularly for Hispanic Americans.