This prospective multicenter cohort study aims to evaluate the effectiveness and safety of early PCSK9 inhibitor therapy in patients with large-artery atherosclerotic ischemic stroke. The study will compare early neurological improvement, lipid-lowering effect, 90-day functional outcome, recurrent cardio-cerebrovascular events, and safety outcomes between patients treated with evolocumab plus statin and those treated with statin alone.
This is a prospective, multicenter, consecutively enrolling cohort study to be conducted at the First Affiliated Hospital of Harbin Medical University and participating centers in Heilongjiang Province. Eligible patients are adults 18-80 years old with acute ischemic stroke of the large-artery atherosclerotic subtype (TOAST classification), LDL-C ≥1.8 mmol/L, and onset-to-enrollment time ≤72 hours. Participants will be assigned to exposure cohorts according to the actual lipid-lowering treatment initiated in routine clinical care. The exposed cohort will receive evolocumab 140 mg subcutaneously every 2 weeks or 420 mg monthly, plus daily statin therapy, for 90 days. The non-exposed cohort will receive daily statin therapy alone for 90 days. The planned total enrollment is 1000 participants, targeting approximately 500 participants per cohort. Visits and assessments will be performed at baseline, Day 7 (±2 days) or hospital discharge, Day 30 (±7 days), and Day 90 (±7 days) after stroke onset. The primary outcome is the proportion of participants with favorable functional outcome (mRS 0-2) at Day 90. Safety follow-up continues through Day 90 whenever feasible, even if evolocumab is discontinued.
Study Type
OBSERVATIONAL
Enrollment
1,000
Harbin, Heilongjiang, China, 150001
Heilongjiang, China
RECRUITINGProportion of participants with favorable functional outcome at Day 90
Proportion of participants with modified Rankin Scale (mRS) score 0-2.
Time frame: 90 ± 7 days after stroke onset
Ordinal distribution of mRS at Day 90
Distribution of mRS scores 0-6 at the 90-day follow-up assessment.
Time frame: 90 ± 7 days after stroke onset
Incidence of early neurologic deterioration (END) and severe END
END: increase of ≥2 points in total NIHSS or ≥1 point in motor subscore within 7 days. Severe END: increase of ≥4 points in total NIHSS or ≥2 points in motor subscore within 7 days.
Time frame: Within 7 days after enrollment
Change in NIHSS score from baseline
Change in NIHSS score from baseline to Day 7 (±2 days) or hospital discharge, whichever comes first.
Time frame: Up to Day 7 (±2 days)
Change in LDL-C from baseline
Change in fasting LDL-C concentration from baseline to the Day 30 follow-up assessment.
Time frame: 30 ± 7 days after stroke onset
Recurrent cardio-cerebrovascular events
Incidence of recurrent ischemic stroke, myocardial infarction, or other adjudicated cardio-cerebrovascular events during follow-up.
Time frame: Within 90 days after stroke onset
All-cause mortality
Death from any cause during follow-up
Time frame: Within 90 days after stroke onset
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