Efficacy and Safety of PCSK9 Inhibitors in Patients With Large-Artery Atherosclerosis (LAA) Ischemic Stroke

1. Age 18-80 years.
2. Acute ischemic stroke diagnosed according to the Chinese Guidelines for Diagnosis and Treatment of Acute Ischemic Stroke (2023), based on clinical and imaging criteria.
3. Large-artery atherosclerotic subtype (TOAST classification) confirmed within 72 hours after stroke onset.
4. NIHSS score 4-20 before treatment.
5. Pre-stroke modified Rankin Scale (mRS) score ≤1.
6. LDL-C ≥1.8 mmol/L before enrollment.
7. Able to use evolocumab and statin medications in accordance with the physician's instructions and the prescribing information.
8. No prior use of a PCSK9 inhibitor before enrollment.
9. Written informed consent provided by the participant or legally authorized representative.

Exclusion Criteria:

1. Hemorrhagic transformation or other intracranial hemorrhage (including hemorrhagic infarction, subarachnoid hemorrhage, subdural hematoma, or epidural hematoma), except cerebral microbleeds detected only by SWI.
2. Prior intracranial or extracranial endovascular therapy before enrollment, planned acute endovascular therapy within 90 days, or planned surgery that may affect outcome assessment.
3. Severe cardiac insufficiency：NYHA class III or IV.
4. Severe hepatic dysfunction (ALT or AST >3 x upper limit of normal) or severe renal dysfunction (serum creatinine >2 mg/dL, eGFR \<30 mL/min/1.73 m2, or requiring dialysis).
5. Platelet count \<100 x 10\^9/L.
6. Pregnancy or breastfeeding.
7. Participation in another interventional clinical study within 30 days before enrollment, or concurrent participation in another interventional study that may affect outcome assessment.
8. Giant intracranial tumor, giant cerebral aneurysm, or arteriovenous malformation.
9. Active gastrointestinal ulcer, active bleeding tendency: corrected international normalized ratio (INR) > 1.5, bleeding time exceeding the upper limit by more than 1 minute, or increased bleeding risk due to heparin-induced thrombocytopenia; major systemic bleeding occurring within 30 days prior to enrollment.
10. Pre-existing neurologic or psychiatric disease likely to affect neurologic or functional outcome assessment; severe neurologic deficit causing loss of independent living; dementia or psychiatric disease preventing completion of follow-up.
11. Autoimmune disease (for example systemic sclerosis, systemic lupus erythematosus, Sjogren syndrome, Behcet disease, mixed connective tissue disease, or IgG4-related disease).
12. Active seizures, hypotension, hyperthyroidism, asthma, and other allergic respiratory diseases, as well as individuals with a tendency toward allergies.
13. Any other condition judged by the investigator to make participation inappropriate or to pose substantial risk.