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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: 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 Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

• Study Contact: Name: Meng Ran, PhD; Phone Number: +86-10-83199280; Email: victor65@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Acute ischemic stroke patients aged 18 to 80 years

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Xuanwu Hospital, Beijing
• Investigators: Study Chair: Meng Ran, PhD, Xuanwu Hospital, Beijing

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2023
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: October 24, 2023
• First Submitted That Met QC Criteria: November 14, 2023
• First Posted (Estimated): November 16, 2023

Study Record Updates

• Last Update Posted (Estimated): November 16, 2023
• Last Update Submitted That Met QC Criteria: November 14, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Statins; Acute Ischemic Stroke; Evolocumab; PCSK9 Inhibitor
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Protease Inhibitors; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Serine Proteinase Inhibitors; PCSK9 Inhibitors; Evolocumab; Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Other Study ID Numbers: RMeng

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No