Upfront Lipid-Lowering Therapy With Statins Combined With Hybutimibe in Patients With Acute Ischemic Stroke or Transient Ischemic Attack.

Inclusion Criteria:

• Definite diagnosis of acute ischemic stroke or TIA.
• Age ≥18 and <75 years
• Time from onset (last known normal) to enrollment ≤ 72 hours.
• LDL-C level ≥ 1.8 mmol/L prior to enrollment (must obtain LDL-C value after onset to be randomized).

Exclusion Criteria:

• Use of high-intensity statins, cholesterol absorption inhibitors, PCSK9 inhibitors, or other small interfering RNA cholesterol-lowering drugs within 14 days prior to randomization.

• Suspected familial hypercholesterolemia.

• Suspected cardiogenic stroke (e.g., with atrial fibrillation, prosthetic heart valves, atrial myxoma, endocarditis).

• Acute ischemic stroke suspected to be caused by other etiologies (e.g., arterial dissection, vasculitis, vascular malformation).

• Presence of isolated sensory symptoms (e.g., numbness) only, isolated visual changes only, or isolated dizziness/vertigo only, in the absence of evidence of acute infarction on baseline head CT or MRI.

• Pre-stroke mRS score >2.

• High risk of cerebral hemorrhage (e.g., imaging indicates hemorrhagic transformation after the current stroke, or history of hemorrhagic stroke).

• Patients with risks or contraindications to statins or hybutimibe:

  1. Acute liver failure or decompensated cirrhosis.
  2. Known hypersensitivity to statins or hybutimibe.
  3. Pregnant or breastfeeding women, or women of childbearing potential who are not using effective contraceptive measures and have no documented pregnancy test.
  4. Use of immunosuppressants, azole antifungals, amiodarone, fibrates, or other medications that may affect statin metabolism within 14 days prior to randomization, or planned use of such medications during the study period.
  5. Hepatic or renal impairment (hepatic impairment defined as ALT >2× upper limit of normal [ULN] or AST >2× ULN; renal impairment defined as serum creatinine >1.5× ULN or estimated glomerular filtration rate [eGFR] <20 mL/min).
  6. Creatine kinase >5× ULN, or a personal or family history of hereditary muscle disease.

• Planned major surgery or interventional procedure within 8 weeks that may require interruption of the study drug.

• Severe organic disease with a life expectancy < 8 weeks.

• Currently participating in other investigational drug or device studies.

• Inability to complete the 8-week follow-up due to geographic or other reasons (e.g., dementia, severe paralysis, psychiatric disorders).