A multicenter cohort study

The trial is to evaluate the effect of ultra-intensive lipid-lowering therapy (PCSK9 inhibitor + rosuvastatin or atorvastatin, with/without ezetimibe) versus conventional lipid-lowering therapy (rosuvastatin or atorvastatin, with/without ezetimibe) on changes in atherosclerotic burden in patients with carotid artery stenosis.

Inclusion Criteria:

Clinical inclusion criteria:

1. Age ≥ 18 years.
2. Asymptomatic mild-to-moderate carotid artery stenosis confirmed by CTA, MRA, ultrasound, or DSA, with no anticipated need for surgical intervention.
3. Modified Rankin Scale (mRS) score ≤ 2
4. Signed informed consent form obtained from the subject

Ultrasound Inclusion Criteria:

Carotid ultrasound showing a plaque burden rate ≥30% at the most stenotic cross-sectional site of the carotid artery (common carotid artery or proximal C1 segment of the internal carotid artery).

Exclusion Criteria:

1. Non-atherosclerotic carotid stenosis, including arterial dissection, Takayasu arteritis, radiation-induced vasculopathy, fibromuscular dysplasia, neurofibromatosis, suspected vasospasm, or recanalized vascular embolism.
2. Known cardioembolic sources: mitral stenosis, mechanical heart valve, infective endocarditis, intracardiac thrombus/vegetation, myocardial infarction within 3 months, dilated cardiomyopathy, chronic/paroxysmal atrial fibrillation. (Confound ASCVD outcome assessment.)
3. History of cerebrovascular, coronary, or peripheral arterial endovascular intervention within 30 days before enrollment or anticipated surgery within the next 6 months.
4. History of ischemic stroke, transient ischemic attack (TIA), or intracranial hemorrhage (parenchymal, subarachnoid, subdural, or epidural) before enrollment.
5. Pre-existing intracranial tumor, cerebral aneurysm, or arteriovenous malformation.
6. History of thromboembolic diseases (pulmonary embolism, mesenteric embolism, lower limb arterial embolism) or coronary atherosclerotic heart disease.
7. Severe neurological deficits impairing independent living; diagnosed dementia/psychiatric disorders interfering with follow-up; or life expectancy <3 years due to other conditions.
8. Severe/unstable comorbidities: Severe heart failure (NYHA Class III/IV or LVEF <30%), Renal failure (serum creatinine >264 μmol/L or creatinine clearance <0.6 mL/s), Severe hepatic dysfunction (ALT/AST >3× upper limit of normal), CK >5× upper limit of normal, Active malignancy.
9. Use of PCSK9 inhibitors or CETP inhibitors within 24 weeks before enrollment.
10. The subjects have taken strong inhibitor drugs of cytochrome P-450 3A4 (including: adagrasib, atazanavir, ceritinib, clarithromycin, darunavir, idelalisib, indinavir, itraconazole, ketoconazole, levonorgestrel, lonafarnib, lopinavir, mifepristone, nefazodone, nelfinavir, nirmatrelvir/ritonavir, Viekira Pak (ombitasvir, paritaprevir, and ritonavir tablets), mbitasvir/paritaprevir/ritonavir and dasabuvir, posaconazole, co-formulations containing ritonavir and ritonavir itself, saquinavir, erythromycin, tucatinib, voriconazole) within one month before randomization, or may require such drugs during the study period.
11. Pregnancy or lactation.
12. Concurrent participation in another trial that may affect outcome assessment.
13. Other situations that the investigator believes may cause significant harm to the subjects if they participate in this trial.
14. Situations where the investigator believes there are other vascular lesions that may lead to short - term ischemic events and surgeries.

For patients with mild to moderate carotid artery stenosis, those who are confirmed to meet the clinical inclusion and exclusion criteria and whose carotid artery plaque burden rate is confirmed to be ≥ 30% through carotid artery ultrasound examination can be registered.

Researchers need to submit a formal data sharing application to the TRIP-CAS Steering Committee and obtain the approval of the Steering Committee.

Data sharing will be available from 12 months after the publication of the main results.

1. The data sharing will be only for the purposes of health and medical research and within the constraints of the consent under which the data were originally gathered.
2. The Custodian of the Collection will not consider any Proposals for data sharing that unblind, or potentially unblind, randomised comparisons in active / ongoing trials.
3. Requesters should be employees of a recognised academic institution, health service organisation, commercial research organisation or from the pharmaceutical industry. Requesters must have experience in medical research. 4.Requesters must be able to demonstrate through their peer review publications in the area of interest their ability to carry out the proposed use of the requested dataset from a Collection.

5.The Requesters must not have a conflict of interest that may potentially influence their interpretation of any analyses.