short-term effect of pcsk9 inhibitor in patients with acute ischemic stroke

Conditions: Acute Ischemic Stroke

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.

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.

Eligibility criteria:
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.

Keywords: acute ischemic stroke evolocumab pcsk9 inhibitor statins