Short-term Effect of PCSK9 Inhibitor in Patients With Acute Ischemic Stroke
- Registration Number
- NCT06134635
- Lead Sponsor
- Xuanwu Hospital, Beijing
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 80
- 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.
- 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.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description PCSK9-i group Evolocumab The participants in PCSK9-i group receive statins and evolocumab for lipid reduction. Statin-alone group Statins The participants in statin-alone group receive statins alone for lipid reduction. PCSK9-i group Statins The participants in PCSK9-i group receive statins and evolocumab for lipid reduction.
- Primary Outcome Measures
Name Time Method LDL-C target achievement rate on Day 5, Month 3 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
- Secondary Outcome Measures
Name Time Method Percentage change in hsCRP level on Day 1, Day 3, Day 5, and Month 3 Day 1, Day 3, Day 5, Month 3 Percentage change in hsCRP level= (follow-up hsCRP level - baseline hsCRP level)/ baseline hsCRP level
Incidence of adverse events on Month 3 Month 3 Adverse events: injection site reaction, anaphylaxis, myopathy, abnormal liver function, new onset diabetes, cognitive impairment, and hemorrhagic cerebral infarction.
Percentage of mRS≤2 on Month 3 Month 3 Percentage of mRS≤2= Number of patients with mRS≤2/ Total number of follow-up patients
Incidence of major cardiovascular events on Month 3 Month 3 Major cardiovascular events: stroke, cardiovascular death, myocardial infarction, hospitalization for unstable angina, and coronary revascularization.
Percentage change in LDL-C level on Day 1, Day 3, Day 5, and Month 3 Day 1, Day 3, Day 5, Month 3 Percentage change in LDL-C level= (follow-up LDL-C level - baseline LDL-C level)/ baseline LDL-C level
Percentage change in HDL-C level on Day 1, Day 3, Day 5, and Month 3 Day 1, Day 3, Day 5, Month 3 Percentage change in HDL-C level= (follow-up HDL-C level - baseline HDL-C level)/ baseline HDL-C level
Percentage change in TG level on Day 1, Day 3, Day 5, and Month 3 Day 1, Day 3, Day 5, Month 3 Percentage change in TG level= (follow-up TG level - baseline TG level)/ baseline TG level
Percentage change in IL-6 level on Day 1, Day 3, Day 5, and Month 3 Day 1, Day 3, Day 5, Month 3 Percentage change in IL-6 level= (follow-up IL-6 level - baseline IL-6 level)/ baseline IL-6 level
Percentage change in TC level on Day 1, Day 3, Day 5, and Month 3 Day 1, Day 3, Day 5, Month 3 Percentage change in TC level= (follow-up TC level - baseline TC level)/ baseline TC level
Percentage change in Apo AI level on Day 1, Day 3, Day 5, and Month 3 Day 1, Day 3, Day 5, Month 3 Percentage change in Apo AI level= (follow-up Apo AI level - baseline Apo AI level)/ baseline Apo AI level
Percentage change in Apo B level on Day 1, Day 3, Day 5, and Month 3 Day 1, Day 3, Day 5, Month 3 Percentage change in Apo B level= (follow-up Apo B level - baseline Apo B level)/ baseline Apo B level