High-Resolution Assessment of Extracranial Plaques in a Multiple Centers Evolocumab Randomized Study

• Evolocumab 140 MG/ML (Drug): Evolocumab 140mg, subcutaneous injection, every 2 weeks, for 26 week, total 13 times
• Intensive statin treatment (Drug): Intensive statin could choose either Atorvastatin 40mg/day or Rosuvastatin 20mg/day, for 26 weeks

Primary outcomes

• Changes of the thickness of fibrous cap of artery plaque measured by OCT [27 Weeks ± 7 days]: Changes of the thickness of fibrous cap of artery plaque measured by OCT

Secondary outcomes

• Changes of the lipid arc of artery plaque measured by OCT [27 Weeks ± 7 days]: Changes of the lipid arc of artery plaque measured by OCT
• Changes of the minimum lumen area (MLA) measured by OCT [27 Weeks ± 7 days]: Changes of the minimum lumen area (MLA) measured by OCT
• Changes of lumen area stenosis measured by OCT [27 Weeks ± 7 days]: Changes of lumen area stenosis measured by OCT
• Changes of the number of microvessels measured by OCT [27 Weeks ± 7 days]: Changes of the number of microvessels measured by OCT
• Changes of the presence and extension of macrophages measured by OCT [27 Weeks ± 7 days]: Changes of the presence and extension of macrophages measured by OCT
• Changes of the calcium aggregation measured by OCT [27 Weeks ± 7 days]: Changes of the calcium aggregation measured by OCT
• Changes of arterial plaque volume measured by OCT [27 Weeks ± 7 days]: Changes of arterial plaque volume measured by OCT
• Changes of lipid necrotic core of arterial plaque measured by OCT [27 Weeks ± 7 days]: Changes of lipid necrotic core of arterial plaque measured by OCT
• Changes of LDL-C levels [27 Weeks ± 7 days]: Changes of LDL-C levels
• Changes of the thickness of minimum fibrous cap of artery plaque measured by 3D-ultrasound [27 Weeks ± 7 days]: Changes of the thickness of minimum fibrous cap of artery plaque measured by 3D-ultrasound
• Changes of arterial plaque volume measured by 3D-ultrasound [27 Weeks ± 7 days]: Changes of arterial plaque volume measured by 3D-ultrasound
• Changes of Lipid necrotic core of arterial plaque measured by 3D-ultrasound [27 Weeks ± 7 days]: Changes of Lipid necrotic core of arterial plaque measured by 3D-ultrasound
• Changes of the thickness of minimum fibrous cap of artery plaque measured by High resolution magnetic resonance [27 Weeks ± 7 days]: Changes of the thickness of minimum fibrous cap of artery plaque measured by High resolution magnetic resonance
• Changes of arterial plaque volume measured by High resolution magnetic resonance [27 Weeks ± 7 days]: Changes of arterial plaque volume measured by High resolution magnetic resonance
• Changes of Lipid necrotic core of arterial plaque measured by High resolution magnetic resonance [27 Weeks ± 7 days]: Changes of Lipid necrotic core of arterial plaque measured by High resolution magnetic resonance
• Correlation between arterial plaque and new risk factors for cardiovascular and cerebrovascular diseases (serum hsCRP, other markers, etc.) [27 Weeks ± 7 days]: Correlation between arterial plaque and new risk factors for cardiovascular and cerebrovascular diseases (serum hsCRP, other markers, etc.)

Other outcomes

• Occurrence of ischemic vascular events [27 Weeks ± 7 days]: Occurrence of ischemic vascular events, such as TIA, acute cerebral infarction, acute myocardial infarction, etc.
• Adverse events/serious adverse events [through study completion, an average of 6 months]: Adverse events/serious adverse events

Sex: All, ages: 18 Years to any

Inclusion Criteria:

1. Age ≥ 18 years old, regardless of sex;
2. Cerebrovascular angiography examination was performed, and the imaging characteristics were consistent with: 1) The stenosis degree of internal carotid artery (starting from C1 segment) or vertebral artery (starting from vertebral artery to V4 segment) was 20%-69%; 2) The target vessel for imaging has not undergone or intends to undergo revascularization and must be available for OCT imaging catheter;
3. Participants who understand and sign the informed consent form voluntarily.

Exclusion Criteria:

1. Intolerant to both atorvastatin and rosuvastatin;
2. History of major surgery or endovascular treatment within 3 months prior to the screening period;
3. Arterial stenosis or occlusion not caused by atherosclerosis, such as arterial dissection, moya-moya disease, vasculitis, radiation vascular disease, or fibromuscular dysplasia;
4. Abnormal liver function (ALT > 3 times the upper limit of normal);
5. Renal dysfunction (glomerular filtration rate (eGFR) <45 mL/min/1.73m2 at screening);
6. Thrombocytopenia (PLT<100G/L);
7. The expected survival time is not more than 6 months;
8. Other known serious life-threatening disease (such as hematologic disease, malignancy), unstable vital signs or need for continuous monitoring, or moribund state during screening;
9. Patients have been included in other studies that conflict with this study;
10. Known sensitivity to any of the products or components to be administered during dosing;
11. Pregnant, breastfeeding or planning pregnancy, and other conditions that the investigator considers the patient unsuitable for enrollment;
12. Other conditions that the investigator considered inappropriate for enrollment.

• Bo Hu, Doctor, Study chair, Union Hospital, Tongji Medical College, Huahzong University of Science and Technology
• Candong Hong, Doctor, Principal investigator, Union Hospital, Tongji Medical College, Huahzong University of Science and Technology
• Lei Zhang, Doctor, Principal investigator, Union Hospital, Tongji Medical College, Huahzong University of Science and Technology
• Quanwei He, Doctor, Principal investigator, Union Hospital, Tongji Medical College, Huahzong University of Science and Technology
• Jiehong Wu, Doctor, Principal investigator, Union Hospital, Tongji Medical College, Huahzong University of Science and Technology