Short-term Effect of PCSK9 Inhibitor in Patients With Acute Ischemic Stroke

Study Overview
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Brief Summary
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This is a prospective cohort study to investigate the early impact of evolocumab on patients with acute ischemic stroke (AIS) in China. Evolocumab, a proprotein convertase subtilisin/kexin taye 9 inhibitor, can significantly reduce low density lipoprotein cholesterol (LDL-C) levels and has a positive effect on improving cardiovascular events. However, existing studies have focused almost exclusively on the long-term effects of Evolocumab, and the early effects of Evolocumab on AIS patients remains unclear.

Detailed Description
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Patients aged 18-80 years old admitted to the Department of Neurology, Xuanwu Hospital, Capital Medical University, with a definite diagnosis of acute ischemic stroke and receiving lipid-lowering therapy with statins with or without evolocumab will be included in this study. Participants will be divided into two groups according to the lipid-lowering therapy they used: 1) statin-alone group: the participants receive statins alone (atorvastatin 20mg qn or rosuvastatin 10mg qn or pivastatin 2mg qn) for lipid reduction, and 2) PCSK9-i group: the participants receive statins (atorvastatin 20mg qn or rosuvastatin 10mg qn or pivastatin 2mg qn) and evolocumab (140mg twice a month) for lipid reduction. Most importantly, the lipid-lowering therapy of participants will be decided only by clinicians not involved in the study, not by the investigators. The levels of blood lipid (TC, TG, HDL-C, LDL-C, Apo AI and Apo B) and inflammatory biomarkers (hsCRP and IL-6) of these participants at different time points (day 1, day 3, day 5, and month 3) will be recorded. The target level of LDL-C is the LDL-C reduction ≥50% from the baseline and LDL-C<1.4mmol/L (55mg/dL). In addition, the cardiovascular events and adverse drug reactions of these participants during follow-up will also be recorded. During the follow-up period (3 months), participants who changed their lipid-lowering regimen, including the type, dosage and frequency of statins and evolocumab, will be excluded from the study.

Official Title
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Short-term Effect of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor in Chinese Population With Acute Ischemic Stroke: the Singe-center Real-world Study

Conditions
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Acute Ischemic Stroke

Intervention / Treatment
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* Drug: Statins
* Drug: Evolocumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with acute ischemic stroke; Aged 18-80 years, gender unlimited; The fasting LDL-C≥1.8mmol/L (70mg/dL); Received lipid-lowering therapy with statins with or without evolocumab; Premorbid mRS ≤ 2; NIHSS ≤ 15; Subjects participated in the study voluntarily and signed informed consent. Exclusion Criteria: Participants who changed their lipid-lowering regimen; Participants allergic to PCSK9 inhibitors; Participants treated with cholesterol ester transfer protein inhibitor within 12 months prior to enrollment; LDL or plasma apheresis within 12 months prior to enrollment； Last known left ventricular ejection fraction < 30% Known hemorrhagic stroke at any time； Severe renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) < 20 mL/min/1.73m2 at final screening； Active liver disease or hepatic dysfunction, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 times； Pregnant or lactating women； Severe, concomitant non-cardiovascular disease that is expected to reduce life expectancy to less than 3 years.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Statin-alone group<br>The participants in statin-alone group receive statins alone for lipid reduction. | Drug: Statins<br>* Atorvastatin 20mg qn or rosuvastatin 10mg qn or pivastatin 2mg qn, oral<br>* Other names: statin therapy;|
| PCSK9-i group<br>The participants in PCSK9-i group receive statins and evolocumab for lipid reduction. | Drug: Statins<br>* Atorvastatin 20mg qn or rosuvastatin 10mg qn or pivastatin 2mg qn, oral<br>* Other names: statin therapy;Drug: Evolocumab<br>* Evolocumab 140mg twice a month, subcutaneous injection<br>* Other names: PCSK9-i;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LDL-C target achievement rate on Day 5, Month 3 | LDL-C target achievement rate= Number of patients who achieved the LDL-C target level/ Total number of follow-up patients | Day 5, Month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change in LDL-C level on Day 1, Day 3, Day 5, and Month 3 | Percentage change in LDL-C level= (follow-up LDL-C level - baseline LDL-C level)/ baseline LDL-C level | Day 1, Day 3, Day 5, Month 3 | 
| Percentage change in HDL-C level on Day 1, Day 3, Day 5, and Month 3 | Percentage change in HDL-C level= (follow-up HDL-C level - baseline HDL-C level)/ baseline HDL-C level | Day 1, Day 3, Day 5, Month 3 | 
| Percentage change in TC level on Day 1, Day 3, Day 5, and Month 3 | Percentage change in TC level= (follow-up TC level - baseline TC level)/ baseline TC level | Day 1, Day 3, Day 5, Month 3 | 
| Percentage change in TG level on Day 1, Day 3, Day 5, and Month 3 | Percentage change in TG level= (follow-up TG level - baseline TG level)/ baseline TG level | Day 1, Day 3, Day 5, Month 3 | 
| Percentage change in Apo AI level on Day 1, Day 3, Day 5, and Month 3 | Percentage change in Apo AI level= (follow-up Apo AI level - baseline Apo AI level)/ baseline Apo AI level | Day 1, Day 3, Day 5, Month 3 | 
| Percentage change in Apo B level on Day 1, Day 3, Day 5, and Month 3 | Percentage change in Apo B level= (follow-up Apo B level - baseline Apo B level)/ baseline Apo B level | Day 1, Day 3, Day 5, Month 3 | 
| Percentage change in hsCRP level on Day 1, Day 3, Day 5, and Month 3 | Percentage change in hsCRP level= (follow-up hsCRP level - baseline hsCRP level)/ baseline hsCRP level | Day 1, Day 3, Day 5, Month 3 | 
| Percentage change in IL-6 level on Day 1, Day 3, Day 5, and Month 3 | Percentage change in IL-6 level= (follow-up IL-6 level - baseline IL-6 level)/ baseline IL-6 level | Day 1, Day 3, Day 5, Month 3 | 
| Percentage of mRS≤2 on Month 3 | Percentage of mRS≤2= Number of patients with mRS≤2/ Total number of follow-up patients | Month 3 | 
| Incidence of major cardiovascular events on Month 3 | Major cardiovascular events: stroke, cardiovascular death, myocardial infarction, hospitalization for unstable angina, and coronary revascularization. | Month 3 | 
| Incidence of adverse events on Month 3 | Adverse events: injection site reaction, anaphylaxis, myopathy, abnormal liver function, new onset diabetes, cognitive impairment, and hemorrhagic cerebral infarction. | Month 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Ischemic Stroke, Evolocumab, PCSK9 Inhibitor, Statins