Evaluation Study of Early Administration of Evolocumab After Thrombolysis in Patients With Atherosclerotic Acute Ischemic Stroke

Inclusion criteria

• Age 18-85 years. No gender or sex restrictions, and no gender ratio restrictions.

• Clinically diagnosed with acute ischemic stroke, with the time from symptom onset to intravenous thrombolysis <9 hours.

• Within 4.5 hours of symptom onset: This time window is based on the ECASS III criteria (Class IA recommendation) and is currently the standard indication for intravenous thrombolysis in acute ischemic stroke worldwide.
• 4.5-9 hours: Referring to the EXTEND study criteria, meeting the following multimodal imaging mismatch ratio: ischemic penumbra volume/ischemic core volume >1.2, with an absolute mismatch volume >10 mL and an ischemic core volume <70 mL.

• The stroke meets the TOAST classification for large artery atherosclerosis (LAA), which includes intracranial arteriosclerosis (ICAS) and extracranial arteriosclerosis (ECAS), and meets one of the following three criteria: large artery stenosis ≥50%, infarct lesion >1.5cm + ipsilateral plaque (no stenosis requirement), or intracranial artery stenosis ≥30% with plaque ulceration.

• The patient or their legal representative has signed an informed consent form.

Exclusion criteria

• CT scan showing signs of intracranial hemorrhage, symptomatic intracranial hemorrhage, or subarachnoid hemorrhage, even if the CT scan results are normal.

• Patients who must or wish to continue using restrictive medications or any medications that may interfere with the safe conduct of the trial.

• Acute bleeding tendency, including but not limited to:

• A known family history of bleeding disorders and a history of a serious bleeding disorder currently present or within the past 6 months.
• Receiving heparin treatment within the past 48 hours, with an activated partial thromboplastin time (aPTT) exceeding the upper limit of the normal range for laboratory testing.
• Currently taking an oral vitamin K anticoagulant (e.g., warfarin) with a prolonged prothrombin time (INR > 1.7 or PT > 15 seconds); or currently taking a novel oral anticoagulant (e.g., dabigatran etexilate, rivaroxaban, or apixaban) with an activated partial thromboplastin time (aPTT) and/or prothrombin time (PT) exceeding the upper limit of the local laboratory reference range.
• Platelet count below 100,000/mm³ at screening.
• History of central nervous system injury (e.g., tumor, aneurysm, intracranial or spinal surgery).
• Experiencing traumatic external cardiac compression, obstetric delivery, or non-compressive vascular puncture (e.g., subclavian or jugular vein puncture) within the past 10 days.
• Known history of suspected intracranial hemorrhage or suspected aneurysm/subarachnoid hemorrhage.
• Tumors with increased bleeding risk.
• History of ulcerative gastrointestinal disease, esophageal varices, aneurysm, or arteriovenous malformation within the past 3 months.
• Associated with bleeding risk. 4. Any known disease significantly associated with this condition.

• Previous mRS score ≥2, with comorbid dementia or other neurodegenerative diseases.

• Clinically confirmed non-atherosclerotic intracranial arterial stenosis, such as aortic dissection, vasculitis, moyamoya disease, embolism, immune system disorders, etc.

• Other comorbid medical histories that may affect endpoint event determination and follow-up, such as history of traumatic brain injury, multiple sclerosis, encephalitis, tumors, poisoning, syphilis, and severe heart, lung, liver, kidney, or endocrine diseases.

• Pregnant women.

• Currently participating in other experimental device or drug studies, or having completed other experimental device or drug studies, or having received other experimental treatments for less than 30 days.

• Having used PCSK9 inhibitors within 4 weeks prior to enrollment.

• Hypersensitivity to statins or PCSK9 inhibitors.

• Patients with severe hepatic or renal impairment (eGFR <30 ml/min/1.73 m²).

• Refusal to sign informed consent.