Statin and Dual Antiplatelet Therapy to Prevent Early Neurological Deterioration in Branch Atheromatous Disease

Prior treatment

• Receipt of any intravenous or intra-arterial thrombolysis within 1 week prior to index event.
• Gastrointestinal bleed or major surgery within 3 months prior to index event.
• Qualifying ischemic event induced by angiography or surgery.
• Anticipated requirement for long-term (\>7 day) non-study antiplatelet drugs (e.g., dipyridamole, ticagrelor, ticlopidine), or NSAIDs.
• Low-density lipoprotein\<70mg/dl without prior statin treatment in recent one year or within 2 days after recruitment

Other illness

• Patients with high risk of cardioembolic source, such as atrial fibrillation, acute myocardial infarction, severe heart failure or valvular heart disease.
• Other determined stroke etiology, such as vasculitis, shock, antiphospholipid antibody syndrome and etc.
• History of nontraumatic intracranial hemorrhage.
• Clear indication for anticoagulation during the study period (deep venous thrombosis, pulmonary embolism or hypercoagulable state).
• Known allergy to clopidogrel, aspirin atorvastatin or rosuvastatin
• Hemostatic disorder or systemic bleeding in the past 3 months
• History of drug-induced hematologic or hepatic abnormalities

Lab values

• Severe renal (serum creatinine \>2 mg/dL) or hepatic insufficiency (INR\>1.2; ALT\>40 U/L or any resultant complication, such as variceal bleeding, encephalopathy, or jaundice)
• Current thrombocytopenia (platelet count \<100 x109/L) or leukopenia (\<2 x109/L)

Age

• Age \< 20 years.

Other

• In the judgment of the treating physician
• A candidate for thrombolysis, endarterectomy or endovascular intervention.
• Patients with more than 50% stenosis of the relevant arteries on magnetic resonance angiography (MRA), including intra- or extra-cranial internal carotid artery, middle cerebral artery or basilar artery.
• Severe non-cardiovascular comorbidity with life expectancy \<3 months.
• Contraindication to clopidogrel, aspirin, atorvastatin or rosuvastatin

• Clinical diagnosis of ischemic stroke with National Institute of Health Stroke Scale (NIHSS) score of 1-8
• An ischemic lesion on diffuse-weighted imaging located in the MCA perforator, or Heubner's artery territories or vertebro-basilar perforator territories at brain stem.
• Branch atheromatous disease, defined by a visible lesion in three or more axial MRI cuts in the MCA perforator or Heubner's artery territories or infarcts that extended from the basal surface of the brainstem.
• Ability to randomize within 24 hours of time last known free of new ischemic symptoms.
• Head CT or MRI ruling out hemorrhage or other pathology, such as vascular malformation, tumor, or abscess, that could explain symptoms or contraindicate therapy.
• Ability to tolerate high intensity medical therapy, including aspirin at a dose of 50-325 mg/day, clopidogrel with 300mg loading and 75mg after day 2 and high-intensity statin(either atorvastatin 40-80mg or rosuvastatin 20 mg/day).
• Pre-stroke mRS≦1