Antiplatelet Therapy and Endothelial-stabilizing Agents in Cerebral Small Vessel Diseases

Inclusion criteria:

1. Age ≥ 30 years and ≤ 79 years.

2. A recent small subcortical infarct that occurred within 3 weeks prior torandomization; or patient with whiter matter hyperintensities with a 2-3 grading onFazekas scale.

3. Absence of signs or symptoms of cortical dysfunction, such as aphasia, apraxia,agnosia, agraphia, homonymous visual field defect.

4. Modified Rankin score of ≤ 4.

5. In the absence of any other pathology in the parent artery at the site of the originof the penetrating artery (focal atheroma, parent vessel dissection, vasculitis,vasospasm, and so on).

6. No ipsilateral cervical carotid stenosis (≥30%) by brain high resolution magneticresonance imaging (HRMRI) or computed tomography angioplasty (CTA) or (magneticresonance angioplasty) MRA and cervical artery ultrasound, if qualifying event ishemispheric. No vertebra artery stenosis (≥30%) by brain HRMRI or CTA or MRA andcervical artery ultrasound, if the lesion is in the territory of posteriorcirculation.

7. No major-risk cardioembolic sources requiring anticoagulation or other specifictherapy.

8. Patient agrees with follow-up visits and is available by phone. 10. Patientunderstands the purpose and requirements of the study, can make him/herselfunderstood, and has signed informed consent.

Exclusion criteria:

1. Intracranial aneurysms that need surgical treatment. Other significant activeneurological illness e.g seizures, multiple sclerosis, intracranial tumor (exceptmeningioma) or any intracranial vascular malformation.

2. Active cardiac disease (atrial fibrillation, myocardial infarct in last six months,active angina, symptomatic cardiac failure).

3. History of any intracranial hemorrhage (parenchymal, subarachnoid, subdural,epidural).

4. Known allergy or contraindication to aspirin, clopidogrel, cilostazol, isosorbidemononitrate or statin.

5. Active peptic ulcer disease, major systemic hemorrhage within 30 days, activebleeding diathesis, platelets < 100,000, hematocrit < 30, international normalizedratio (INR) > 1.5, clotting factor abnormality that increases the risk of bleeding,current alcohol or substance abuse, uncontrolled severe hypertension (systolicpressure > 180 mm Hg or diastolic pressure > 115 mm Hg), severe liver impairment (aspartate transaminase [AST] or alanine transaminase [ALT] > 3 x normal,cirrhosis), creatine kinase > 5 times the upper limit of normal (ULN) at finalscreening, severe renal dysfunction, defined as an estimated glomerular filtrationrate (eGFR) < 20mL/min/1.73 square meter at final screening.

6. Major surgery (including open femoral, aortic, cardiac or carotid surgery) withinprevious 30 days or planned in the 1 year after enrollment.

7. Dementia or psychiatric problem that prevents the patient from relevant evaluationor follow-up reliably.

8. Co-morbid conditions that may limit survival to less than 1 year.

9. Currently breastfeeding, pregnancy, planning to become pregnant and unwilling to usecontraception for the duration of this study

10. Unable to tolerate, or contraindication to, MRI.

11. Enrollment in another study that would conflict with the current study.