Evolocumab Added to Statin Therapy in Symptomatic Intracranial Atherosclerotic Stenosis (EAST-ICAS) (EAST-ICAS)

Inclusion criteria: Age ≥ 30 years and ≤ 75 years. TIA or Acute ischemic stroke that occurred within 6 weeks prior to randomization. Modified Rankin score of ≤ 4. TIA or acute ischemic stroke attributed to a 50 to 99% stenosis of a major intracranial artery (internal carotid artery [ICA], vertebral artery [VA], basilar artery [BA] and the M1 segment of middle cerebral artery [MCA]). The diagnostic evaluation for ICAS at each site is confirmed by the local investigator, using high resolution MR. To increase the likelihood that the symptomatic intracranial stenosis is atherosclerotic, patients aged 30-49 years are required to meet at least one additional criteria (i-vi) below: i. insulin dependent diabetes for at least 15 years. ii. at least 2 of the following atherosclerotic risk factors: hypertension (Blood pressure [BP] ≥ 140/90 or on antihypertensive therapy); dyslipidemia (LDL ≥ 130 mg /dl or high density lipoprotein (HDL) < 40 mg/dl or fasting triglycerides ≥150 mg/dl or on lipid lowering therapy); smoking; non-insulin dependent diabetes or insulin dependent diabetes of less than 15 years duration; family history of any of the following: myocardial infarction, coronary artery bypass, coronary angioplasty or stenting, stroke, carotid endarterectomy or stenting, peripheral vascular surgery in parent or sibling who was < 55 years of age for men or < 65 for women at the time of the event. iii. history of any of the following: myocardial infarction, coronary artery bypass, coronary angioplasty or stenting, carotid endarterectomy or stenting, or peripheral vascular surgery for atherosclerotic disease. iv. any stenosis of an extracranial carotid or vertebral artery, another intracranial artery, subclavian artery, coronary artery, iliac or femoral artery, other lower or upper extremity artery, mesenteric artery, or renal artery that was documented by non-invasive vascular imaging or catheter angiography and is considered atherosclerotic. v. aortic arch atheroma documented by non-invasive vascular imaging or catheter angiography. vi. any aortic aneurysm documented by non-invasive vascular imaging or catheter angiography that is considered atherosclerotic. Patient agrees with follow-up visits and is available by phone. Patient understands the purpose and requirements of the study, can make him/herself understood, and has signed informed consent. Exclusion criteria Previous treatment of target intracranial lesion with a stent, angioplasty, or other mechanical devices (e.g. mechanical thrombectomy, coil embolization). Plan to perform angioplasty, stenting, coiling, thrombectomy, endarterectomy or aneurysmal coil embolization for target vessels/plaques. In case that patients who receive surgeries during follow-up, they will still be followed up for 1 year. Intracranial tumor (except meningioma) or any intracranial vascular malformation. History of any intracranial hemorrhage (parenchymal, subarachnoid, subdural, epidural). Intracranial arterial stenosis due to arterial dissection; MoyaMoya disease; any known vasculitic disease; viral vasculopathy; neurosyphilis; any other intracranial infection; any intracranial stenosis associated with cerebral spinal fluid pleocytosis; radiation induced vasculopathy; fibromuscular dysplasia; sickle cell disease; neurofibromatosis; benign angiopathy of central nervous system; postpartum angiopathy; suspected vasospastic process; reversible cerebral vasoconstriction syndrome (RCVS); suspected recanalized embolus. Presence of any of the following unequivocal cardiac sources of embolism: chronic or paroxysmal atrial fibrillation, mitral stenosis, mechanical valve, endocarditis, intracardiac clot or vegetation, myocardial infarction within three months, dilated cardiomyopathy, left atrial spontaneous echo contrast, ejection fraction less than 30%. Use of cholesteryl ester transfer protein (CETP) inhibition treatment, mipomersen, or lomitapide within 12 months prior to randomization. Fenofibrate therapy must be stable for at least 6 weeks prior to final screening at a dose that is appropriate for the duration of the study in the judgment of the investigator. Other fibrate therapy (and derivatives) are prohibited. Prior use of PCSK9 inhibition treatment before this recruitment. Known allergy or contraindication to aspirin, clopidogrel, evolocumab or atorvastatin. 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. Major surgery (including open femoral, aortic, cardiac or carotid surgery) within previous 30 days or planned in the 1 year after enrollment. Dementia or psychiatric problem that prevents the patient from relevant evaluation or follow-up reliably. Co-morbid conditions that may limit survival to less than 1 year. Currently breastfeeding, pregnancy, planning to become pregnant and unwilling to use contraception for the duration of this study Enrollment in another study that would conflict with the current study.