INtensive liPid-lowering Therapy for Acute High-risk IntracRanial or Extracranial atheroSclerosis -II (INSPIRES-2)

The research team is conducting a randomized, double-blind, placebo-controlled, multicenter clinical study aimed at evaluating the impact of adding Tolecilimab (a PCSK9 inhibitor) to standard lipid-lowering therapy (statins ± ezetimibe) on serum lipoprotein(a) \[Lp(a)\] levels and the risk of stroke recurrence within 90 days in patients with ischemic stroke or high-risk TIA (ABCD² ≥ 4) accompanied by elevated lipoprotein(a) levels (≥30 mg/dL).

Inclusion Criteria: 1. Age between 35 and 80 years, regardless of gender. 2. For patients with prior lipid-lowering treatment: screening LDL-C ≥1.8 mmol/L; for treatment-naïve patients: screening LDL-C ≥2.6 mmol/L. 3. Lp(a) ≥30 mg/dL. 4. Onset of symptoms within 3 to 7 days. 5. Diagnosis of ischemic stroke (NIHSS score ≤20) or high-risk TIA with ABCD² score ≥4; and meeting at least one of the following imaging criteria: (1) Large-artery atherosclerosis (LAA) subtype per TOAST classification: vascular imaging confirms ≥50% atherosclerotic stenosis of the intracranial or extracranial culprit artery. (2) Head CT or MRI demonstrates acute multiple infarcts, with etiology consistent with large-artery atherosclerosis (including nonstenotic vulnerable plaques). 6.The patient or their legally authorized representative has provided written informed consent. Exclusion Criteria: 1. Have received or are planned to receive intravenous thrombolysis or endovascular thrombectomy; 2. Definite cardioembolic ischemic cerebrovascular disease, such as that associated with atrial fibrillation, prosthetic heart valves, atrial myxoma, endocarditis, etc.; 3. Ischemic cerebrovascular disease with other definite etiologies, such as aortic dissection, cervical or intracranial arterial dissection, vasculitis, vascular malformation, moyamoya disease/moyamoya syndrome, fibromuscular dysplasia, etc.; 4. Non-vascular intracranial diseases, such as intracranial tumors, multiple sclerosis, etc.; 5. Neuroimaging showing that the infarct area of the index cerebral infarction involves more than one-half of a single cerebral lobe; 6. Neuroimaging showing hemorrhagic transformation of the index cerebral infarction; 7. Pre-stroke modified Rankin Scale (mRS) score \>1; 8. Known hypersensitivity to tafolecimab or any other contraindication to its use; 9. Use of immunosuppressive agents, antifungal agents, fibrates, or other medications that may affect statin metabolism within 14 days prior to randomization; 10. Creatine kinase (CK) level \>5 times the upper limit of normal (ULN) after symptom onset; 11. Severe hepatic or renal impairment prior to randomization. Severe hepatic impairment is defined as alanine aminotransferase (ALT) \>2 times the ULN or aspartate aminotransferase (AST) \>2 times the ULN; severe renal impairment is defined as serum creatinine \>1.5 times the ULN or glomerular filtration rate (GFR) \