Inclusion criteria:
1. Age ≥ 30 years and ≤ 79 years.
2. A recent small subcortical infarct that occurred within 3 weeks prior to randomization; or patient with whiter matter hyperintensities with a 2-3 grading on Fazekas 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 origin of the penetrating artery (focal atheroma, parent vessel dissection, vasculitis, vasospasm, and so on).
7\. No ipsilateral cervical carotid stenosis (≥30%) by brain high resolution magnetic resonance imaging (HRMRI) or computed tomography angioplasty (CTA) or (magnetic resonance angioplasty) MRA and cervical artery ultrasound, if qualifying event is hemispheric. No vertebra artery stenosis (≥30%) by brain HRMRI or CTA or MRA and cervical artery ultrasound, if the lesion is in the territory of posterior circulation.
8\. No major-risk cardioembolic sources requiring anticoagulation or other specific therapy.
9\. Patient agrees with follow-up visits and is available by phone. 10. Patient understands the purpose and requirements of the study, can make him/herself understood, and has signed informed consent.
Exclusion criteria:
1. Intracranial aneurysms that need surgical treatment. Other significant active neurological illness e.g seizures, multiple sclerosis, intracranial tumor (except meningioma) 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, isosorbide mononitrate or statin.
5. Active peptic ulcer disease, major systemic hemorrhage within 30 days, active bleeding diathesis, platelets \< 100,000, hematocrit \< 30, international normalized ratio (INR) \> 1.5, clotting factor abnormality that increases the risk of bleeding, current alcohol or substance abuse, uncontrolled severe hypertension (systolic pressure \> 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 final screening, severe renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) \< 20mL/min/1.73 square meter at final screening.
6. Major surgery (including open femoral, aortic, cardiac or carotid surgery) within previous 30 days or planned in the 1 year after enrollment.
7. Dementia or psychiatric problem that prevents the patient from relevant evaluation or 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 use contraception 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.
