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

Sponsor

Xuanwu Hospital, Beijing (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06134635

Collaborator

(none)

Enrollment

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Ischemic Stroke	Drug: Statins Drug: Evolocumab

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

80 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Anticipated Study Start Date :

Dec 1, 2023

Anticipated Primary Completion Date :

Nov 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

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

Arm

Intervention/Treatment

Statin-alone group

The participants in statin-alone group receive statins alone for lipid reduction.

Drug: Statins

Atorvastatin 20mg qn or rosuvastatin 10mg qn or pivastatin 2mg qn, oral

Other Names:

statin therapy

PCSK9-i group

The participants in PCSK9-i group receive statins and evolocumab for lipid reduction.

Drug: Statins

Atorvastatin 20mg qn or rosuvastatin 10mg qn or pivastatin 2mg qn, oral

Other Names:

statin therapy

Drug: Evolocumab

Evolocumab 140mg twice a month, subcutaneous injection

Other Names:

PCSK9-i

Outcome Measures

Primary Outcome Measures

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

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 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 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 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
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
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 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.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.