Small subcortical strokes (S3), also known as lacunar infarcts, comprise nearly 25 percent of brain infarcts, are harbingers of vascular dementia, and are particularly frequent in Mexican- Americans. Combination antiplatelet therapy using clopidogrel plus aspirin and intensive lowering of blood pressure could substantially reduce major vascular events and cognitive decline in S3 patients. However, a large randomized clinical trial is required to define the efficacy and safety of these interventions specifically in patients with S3 due to presumed small vessel disease. This proposal is for a pilot study to: 1. Determine the lowest tolerable, achievable target blood pressures among survivors of S3. 2. To assess whether the difference between the lowest tolerable blood pressures are sufficiently different from that achieved by standard targets to substantially impact the occurrence of subsequent stroke and cognitive decline. 3. To quantitatively assess white matter abnormalities in S3 patient by serial MRI, correlating these with patient features, cognitive status, blood pressure control and antiplatelet treatment. 4. To assess the relationship of Mexican-American ethnicity to blood pressure interventions, tolerance of antiplatelet therapy, extent and progression of white matter abnormalities, and cognitive status, as well as to modify and assess existing screening tests of cognitive status for those who primarily speak Spanish. Participants with S3 attributed to small vessel disease will be randomized to treatment with aspirin (650mg/d) or aspirin plus clopidogrel (75mg/d) (double-blind), while those with a history of hypertension will additionally be randomized to three different target levels of blood pressure lowering (not blinded). The tolerance and achieved blood pressures in each target level will be the primary outcome, with tolerance and side-effects of antiplatelet therapy also assessed. Quantitative MRI will be done at entry and after a mean of one year, correlated with cognitive status, interventions and ethnicity. No clinical trials have assessed secondary prevention in S3, the most common type of stroke in Mexican Americans and accounting for about 150,000 strokes yearly in the US. While this pilot study is a necessary first-step for a larger, definitive clinical trial, valuable and unique information about blood pressure control after stroke and about issues relevant to stroke prevention in Mexican-Americans will emerge.
