• Evidence of clinically defined ischemic stroke (focal neurological deficits persisting for more than 24 hours) confirmed by non-investigational CT or MRI [ Time Frame: Mean follow up of 3 years ] [ Designated as safety issue: Yes ]
• Evidence of hemorrhagic stroke; a neurologic deficit associated with intraparenchymal or subarachnoid space lesion on CT/MRI or cerebral hemorrhage demonstrated by surgery or autopsy. [ Time Frame: within mean follow-up of 3 years ] [ Designated as safety issue: Yes ]

The goal of this study is to learn if combination antiplatelet therapy (aspirin and clopidogrel) is more effective than aspirin alone for the prevention of recurrent stroke and cognitive decline, and if intensive blood pressure control is associated with fewer recurrent strokes and cognitive decline.

Stroke is damage to the brain caused by problems in the blood vessels. Strokes often cause paralysis, loss of sensation and speech, and other problems. A lacunar or small Subcortical stroke affects the inner part of the brain causing small "pea sized" areas of damage due to blockage of small blood vessels within the brain.

This multi-center study will recruit 2500 participants (20 percent of whom will be Hispanic Americans) to find out if using aspirin and clopidogrel is more effective than using aspirin alone to prevent recurrent stroke in patients with lacunar stroke confirmed by MRI, and if lowering a patient's blood pressure below the usual limits will also help prevent recurrent stroke and maintain thinking ability. Both aspirin and clopidogrel are widely-used for blood clotting and stroke prevention. Investigators intend to find out if using the drugs together is more effective than using aspirin alone.

Participants will be randomly assigned to one of 2 types of treatment: either aspirin alone or the combination of aspirin and clopidogrel. In addition, participants will be assigned to one of 2 groups of blood pressure control. The difference between the two groups is the target level of systolic blood pressure—either 130-149 or below 130. The goal of the blood pressure aspect of this trial is to find out if lowering blood pressure after stroke helps to prevent recurrent stroke and preserves cognition.

• Cerebrovascular Accident
• Hypertension

• Drug: aspirin
• Drug: clopidogrel
• Other: Target of Blood Pressure
• Other: placebo

• Active Comparator: Participants receive aspirin + placebo OR aspirin + clopidogrel
• Active Comparator: The goal of the blood pressure aspect of this trial is to find out if lowering blood pressure after stroke helps to prevent recurrent stroke and preserves cognition.

INCLUSION:

Inclusion criteria are based on TOAST criteria supplemented by required MRI data. All of the following criteria must be met:

• One of the lacunar stroke clinical syndromes (adapted from Fisher) lasting > 24 hrs within the past 6 months
• Absence of signs or symptoms of cortical dysfunction such as aphasia, apraxia, agnosia, agraphia, homonymous visual field defect, etc.
• No ipsilateral cervical carotid stenosis (≥50%) by a reliable imaging modality done in an approved laboratory since the qualifying small subcortical stroke (S3), if hemispheric.
• No major-risk cardioembolic sources requiring anticoagulation or other specific therapy. Minor-risk cardioembolic sources will be permitted if anticoagulation is not prescribed by the patient's primary care physician.
• Subcortical TIA with corresponding lesion on DWI.
• MRI evidence of S3: a. Presence of an S3 (1.5 and 2 cm in diameter corresponding to the qualifying event on DWI; when TIA, ADC image must confirm lesion or T2/FLAIR (hyperintense lesions) (required for all brainstem events) OR multiple S3s on FLAIR/TI(<1.5 cm in diameter) (hypointense lesions) b. Absence of cortical stroke and large subcortical stroke (recent or remote).

EXCLUSION:

To be eligible for entry into the study, the patient must not meet any of the criteria listed below:

• Disabling stroke (Modified Rankin Scale <4)
• Previous intracranial hemorrhage (excluding traumatic) or hemorrhagic stroke
• Age under 40 years
• High risk of bleeding (e.g. recurrent GI or GU bleeding, active peptic ulcer disease, etc)
• Anticipated requirement for long-term use of anticoagulants (e.g. recurrent DVT) or other antiplatelets
• Prior cortical stroke (diagnosed either clinically or by neuroimaging), or prior cortical or retinal TIA
• Prior ipsilateral carotid endarterectomy
• Impaired renal function: GFR <40
• Intolerance or contraindications to aspirin or clopidogrel (including thrombocytopenia, prolonged INR)
• A score < 24 (adjusted for age and education) on the Folstein Mini Mental Status Examination
• Medical contraindication to MRI
• Pregnancy or women of child-bearing potential who are not following an effective method of contraception
• Geographic or social factors making study participation impractical
• Unable or unwilling to provide informed consent
• Unlikely to be compliant with therapy/unwilling to return for frequent clinic visits
• Patients concurrently participating in another study with an investigational drug or device
• Other likely specific cause of stroke (e.g. dissection, vasculitis, prothrombotic diathesis, drug abuse)