PCSK9 Inhibitor With Statin Therapy for Asymptomatic Intracranial Atherosclerosis

Exclusion Criteria19

• Non-atherosclerotic intracranial artery stenosis, including arterial dissection; moya moya disease; systemic vasculitis and primary central nervous system vasculitis; varicella-zoster vasculopathy or other viral vasculopathy; neurosyphilis and other intracranial infections, radiation vasculopathy; fibromuscular dysplasia, sickle cell disease, neurofibromatosis; reversible cerebral vasoconstriction syndrome; postpartum vasculopathy; suspected vasospasm, suspected reperfusion after vessel occlusion.
• Upstream tandem extracranial vessel stenosis (≥50%) adjacent to the target intracranial stenotic vessel.
• Previous treatment of target intracranial lesion with endovascular intervention or plan to perform endovascular intervention within 6 months, including intracranial stenting, endovascular angioplasty, and thrombectomy.
• Any intracranial hemorrhage (parenchymal, subarachnoid, subdural, extradural, intraventricular) within 90 days prior to enrollment.
• Presence of intracranial tumors.
• Presence of cerebral aneurysms or arteriovenous malformations with indications for interventional therapy.
• Major surgery (including open femoral, aortic, or carotid surgery) within previous 30 days or planned in the next 6 months after enrollment.
• Presence of any of the following unequivocal cardiac sources of embolism: mitral stenosis, mechanical valve, endocarditis, intracardiac clot or vegetation, myocardial infarction within 3 months, dilated cardiomyopathy, chronic or paroxysmal atrial fibrillation.
• New York Heart Association (NYHA) class III or IV, or known left ventricular ejection fraction \< 30%.
• Severe liver dysfunction or severe kidney dysfunction: AST and/or ALT \> 3 times the ULN; creatinine clearance \< 0.6 mL/s and/or serum creatinine \> 265 μmol/L (\>3.0 mg/dL); CK \>5 times the ULN at screening.
• Active bleeding diathesis or coagulopathy (e.g., active peptic ulcer disease, major systemic hemorrhage within 30 days, active bleeding diathesis, platelets count \< 125,000 / uL, hematocrit \< 30%, Hgb \< 10 g/dl, international normalized ratio \>1.5, bleeding time \> 1 minute beyond normal value upper limit).
• Presence of systemic autoimmune diseases: systemic sclerosis, systemic lupus erythematosus, Sjögren's syndrome, Behçet's disease, mixed connective tissue disease, IgG4-related disease.
• Dementia or psychiatric problem that hinder their ability to consistently adhere to an outpatient program. Co-morbid conditions that may limit the life expectancy to less than 3 years.
• Relative/absolute contraindications to magnetic resonance imaging (MRI) (such as presence of internal metallic objects, claustrophobia, contrast agent allergy, severe renal impairment, epilepsy, hypotension, asthma, and other hypersensitivity respiratory diseases).
• Uncontrolled hypertension during the screening period, defined as seated systolic blood pressure (SBP) \> 180 mmHg or diastolic blood pressure (DBP) \> 110 mmHg.
• Prior use of PCSK9 inhibitor before this recruitment.
• Known intolerance or allergy to statin.
• Pregnancy, lactation, or planning pregnancy.
• Currently participating in another study.