This prospective multicenter cohort study aims to evaluate the effectiveness and safety of early PCSK9 inhibitor therapy in patients with large-artery atherosclerotic ischemic stroke. The study will compare early neurological improvement, lipid-lowering effect, 90-day functional outcome, recurrent cardio-cerebrovascular events, and safety outcomes between patients treated with evolocumab plus statin and those treated with statin alone.

This is a prospective, multicenter, consecutively enrolling cohort study to be conducted at the First Affiliated Hospital of Harbin Medical University and participating centers in Heilongjiang Province. Eligible patients are adults 18-80 years old with acute ischemic stroke of the large-artery atherosclerotic subtype (TOAST classification), LDL-C ≥1.8 mmol/L, and onset-to-enrollment time ≤72 hours. Participants will be assigned to exposure cohorts according to the actual lipid-lowering treatment initiated in routine clinical care.

The exposed cohort will receive evolocumab 140 mg subcutaneously every 2 weeks or 420 mg monthly, plus daily statin therapy, for 90 days. The non-exposed cohort will receive daily statin therapy alone for 90 days. The planned total enrollment is 1000 participants, targeting approximately 500 participants per cohort. Visits and assessments will be performed at baseline, Day 7 (±2 days) or hospital discharge, Day 30 (±7 days), and Day 90 (±7 days) after stroke onset. The primary outcome is the proportion of participants with favorable functional outcome (mRS 0-2) at Day 90. Safety follow-up continues through Day 90 whenever feasible, even if evolocumab is discontinued.

Inclusion Criteria:

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.

The study population consists of adult patients aged 18-80 years with acute ischemic stroke of the large-artery atherosclerotic (LAA) subtype, confirmed by clinical and imaging criteria within 72 hours of symptom onset. Eligible participants have baseline LDL-C ≥1.8 mmol/L, NIHSS score 4-20, and a pre-stroke modified Rankin Scale (mRS) score ≤1. Patients are consecutively enrolled from multiple tertiary hospitals in Heilongjiang Province during routine clinical care. All participants are candidates for statin therapy, with or without PCSK9 inhibitor (evolocumab), based on the actual clinical diagnosis and treatment plan. Key exclusions include intracranial hemorrhage, severe cardiac insufficiency, severe hepatic or renal dysfunction, major comorbidities affecting outcomes, and prior PCSK9 inhibitor use.