Early evolocumab plus statin for large-artery ischemic stroke

Efficacy and Safety of PCSK9 Inhibitors in Patients With Large-Artery Atherosclerosis (LAA) Ischemic Stroke: A Prospective Multicenter Cohort Study

This will test whether giving evolocumab with a statin soon after a large-artery ischemic stroke helps people recover better than a statin alone.

Quick facts

• Study type: Observational
• Enrollment: 1000 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: First Affiliated Hospital of Harbin Medical University (Academic / other)
• Drugs / interventions: evolocumab
• Locations: 1 site (Heilongjiang)
• Trial ID: NCT07540741 on ClinicalTrials.gov

What this trial studies

This prospective multicenter cohort will compare outcomes for patients with large-artery atherosclerotic ischemic stroke who receive early evolocumab plus a statin versus a statin alone. Adults 18–80 with LDL-C ≥1.8 mmol/L and symptom onset within 72 hours will be enrolled at the First Affiliated Hospital of Harbin Medical University and other centers in Heilongjiang Province and assigned to exposure cohorts based on the lipid-lowering treatment started in routine care. The evolocumab group receives 140 mg every 2 weeks or 420 mg monthly plus daily statin for 90 days while the non-exposed group receives daily statin alone for 90 days. Primary outcome is favorable functional outcome (mRS 0–2) at Day 90 with visits at baseline, Day 7, Day 30, and Day 90 and safety monitored through Day 90.

Who should consider this trial

Good fit: Adults 18–80 with acute large-artery atherosclerotic ischemic stroke (TOAST LAA) within 72 hours, LDL-C ≥1.8 mmol/L, NIHSS 4–20, pre-stroke mRS ≤1, and no prior PCSK9 inhibitor are the intended participants.

Not a fit: Patients with hemorrhagic transformation or other intracranial hemorrhage, non-LAA stroke subtypes, very severe strokes outside the NIHSS range, LDL-C below 1.8 mmol/L, or contraindications to PCSK9 inhibitors are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, early addition of evolocumab could improve 90-day functional recovery and reduce recurrent vascular events in people with large-artery ischemic stroke.

How similar studies have performed: PCSK9 inhibitors have proven cardiovascular benefit by lowering LDL-C and reducing atherosclerotic events, but early use after acute large-artery ischemic stroke to improve 90-day functional outcomes is relatively untested.

Eligibility criteria

Inclusion Criteria:

1. Age 18-80 years.
2. Acute ischemic stroke diagnosed according to the Chinese Guidelines for Diagnosis and Treatment of Acute Ischemic Stroke (2023), based on clinical and imaging criteria.
3. Large-artery atherosclerotic subtype (TOAST classification) confirmed within 72 hours after stroke onset.
4. NIHSS score 4-20 before treatment.
5. Pre-stroke modified Rankin Scale (mRS) score ≤1.
6. LDL-C ≥1.8 mmol/L before enrollment.
7. Able to use evolocumab and statin medications in accordance with the physician's instructions and the prescribing information.
8. No prior use of a PCSK9 inhibitor before enrollment.
9. Written informed consent provided by the participant or legally authorized representative.

Exclusion Criteria:

1. Hemorrhagic transformation or other intracranial hemorrhage (including hemorrhagic infarction, subarachnoid hemorrhage, subdural hematoma, or epidural hematoma), except cerebral microbleeds detected only by SWI.
2. Prior intracranial or extracranial endovascular therapy before enrollment, planned acute endovascular therapy within 90 days, or planned surgery that may affect outcome assessment.
3. Severe cardiac insufficiency：NYHA class III or IV.
4. Severe hepatic dysfunction (ALT or AST \>3 x upper limit of normal) or severe renal dysfunction (serum creatinine \>2 mg/dL, eGFR \<30 mL/min/1.73 m2, or requiring dialysis).
5. Platelet count \<100 x 10\^9/L.
6. Pregnancy or breastfeeding.
7. Participation in another interventional clinical study within 30 days before enrollment, or concurrent participation in another interventional study that may affect outcome assessment.
8. Giant intracranial tumor, giant cerebral aneurysm, or arteriovenous malformation.
9. Active gastrointestinal ulcer, active bleeding tendency: corrected international normalized ratio (INR) \> 1.5, bleeding time exceeding the upper limit by more than 1 minute, or increased bleeding risk due to heparin-induced thrombocytopenia; major systemic bleeding occurring within 30 days prior to enrollment.
10. Pre-existing neurologic or psychiatric disease likely to affect neurologic or functional outcome assessment; severe neurologic deficit causing loss of independent living; dementia or psychiatric disease preventing completion of follow-up.
11. Autoimmune disease (for example systemic sclerosis, systemic lupus erythematosus, Sjogren syndrome, Behcet disease, mixed connective tissue disease, or IgG4-related disease).
12. Active seizures, hypotension, hyperthyroidism, asthma, and other allergic respiratory diseases, as well as individuals with a tendency toward allergies.
13. Any other condition judged by the investigator to make participation inappropriate or to pose substantial risk.

Where this trial is running

Heilongjiang

• Harbin, Heilongjiang, China, 150001 — Heilongjiang, China (Recruiting)

Study contacts

• Principal investigator: Zhongling Zhang — First Affiliated Hospital, Harbin Medical University
• Study coordinator: Zhongling Zhang

Conditions Acute Ischemic Stroke; PCSK9 inhibitor; Cohort study; Large-Artery Atherosclerotic; Functional outcome