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

Xuanwu Hospital, Beijing80 enrolled

Overview

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.

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

Conditions

Acute Ischemic Stroke

Interventions

StatinsDRUG

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

EvolocumabDRUG

Evolocumab 140mg twice a month, subcutaneous injection

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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

Time frame: Day 5, Month 3

Secondary Outcomes

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