Effects of Early Atorvastatin Treatment During the Acute Phase of Stroke on Immunoinflammatory Markers and Outcome in Patients With Acute Ischemic Stroke Classified as LAAS According TOAST Classification
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- differences in msRankin score
研究概览
简要总结
Recent clinical trials and meta-analyses of b-hydroxy-bmethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have demonstrated a significant reduction in ischemic stroke in patients with a history of coronary artery disease, both with and without elevations of serum cholesterol. Recent data suggest that statins have other beneficial properties in addition to the retardation of atherosclerosis. Asahi et al demonstred that Statins increased eNOS and tPA mRNA levels but did not change mRNA levels of PAI-1 and that In eNOS knockout mice, atorvastatin reduced the volume of ischemic tissue and improved neurologic outcomes after arterial occlusion by blood clot emboli. In addition to their lipid-lowering effects, it has been speculated that statins may also have beneficial effects on cerebral circulation and brain parenchyma during ischaemic stroke and reperfusion. Aslanyan et al reported that statin use was associated with reduced mortality at 1 month during the follow-up.
In patients with recent stroke or TIA and without known coronary heart disease, 80 mg of atorvastatin per day reduced the overall incidence of strokes and of cardiovascular events, despite a small increase in the incidence of hemorrhagic stroke period .
Recently the investigators group reported that lacunar strokes compared to nonlacunar ones exhibited significantly lower plasma levels of TNF-α and IL1-β, P-selectin and ICAM-1 24-72 h and 7-10 days after stroke onset (4). At extracranial arterial territories, inflammation plays a crucial role mediating all the stages of the atherosclerosis process . Similarly, thrombosis and defective fibrinolysis may also contribute to the progression of atherosclerotic lesions . Interestingly, both mechanisms might have a relevant role in the pathogenesis of intracranial large artery atherosclerosis and ischemic stroke Moreover our group showed that Patients with cardioembolic and atherothrombotic stroke subtypes showed significantly higher median plasma levels of TNF-α, IL-6, IL-1β whereas the lacunar subtype showed significantly lower median plasma levels of TNF-α, IL-6 and IL-1β and that immunoinflammatory marker plasma levels are significantly related to ischemic lesion volume.
A meta-analysis showed that statins may possess antithrombotic property because these drugs were reported to reduce periprocedural infarction in patients undergoing percutaneous coronary intervention .
This clinical benefit was detected after median, 0.5 days of treatment with statins (indicating that statins could potentially exert an antithrombotic effect even earlier than supposed from pharmacological studies.
Violi et al recently showed the first evidence that atorvastatin acutely and simultaneously decreases oxidative stress and platelet activation by directly inhibiting platelet Nox2 and ultimately platelet isoprostanes and thromboxane A2 so providinf a rationale for the use of statins to prevent or modulate coronary thrombosis.
Whereas recent data suggest that inflammatory reactions are involved in the pathogenesis and progression of cerebral ischaemia , no study has evaluated effects of atorvastatin 80 mg/day after a recent stroke on stroke outcome and on immunoinflammatory markers so to evaluate acute antithrombotic and anti-inflammatory effects of atorvastatin also in acute cerebrovascular event setting.
On this basis the primary objective of the study was to evaluate the separate effects of atorvastatin in vivo on immunoinflammatory markers and on stroke prognosis in patients with recent acute ischemic stroke classified as atherothrombotic.
详细描述
Material and Methods The investigators will enroll patients with a diagnosis of acute ischemic stroke admitted to the Internal Medicine Department at the University of Palermo between November 2011 and October 2014. The controlsubjects were patients admitted, in the same period, to our Internal Medicine Department for any cause different from acute cardiovascular and cerebrovascular events or exclusion criteria. Every subject with ischemic stroke was matched for age (±3 years), sex, and cardiovascular risk factor prevalence with one control subject
Study Hypothesis and Patient Population:
The primary hypothesis of the study is that treatment with 80 mg of atorvastatin per day administered early at admission after acute ischemic stroke would reduce immunoinflammatory activation of the acute phase and that this immunoinflammatory modulation could have a possible effect on prognosis of ischemic stroke evaluated by some outcome indicators.
Eligible patients are men and women over 18 years of age who had an acute ischemic stroke Patients with inflammatory or infectious diseases, cancer, hematological diseases and severe renal or liver failure, as well as those who were under treatment with anti-inflammatory will be excluded Stroke was defined by focal neurological signs or symptoms thought to be of vascular origin that persisted for >24 h, confirmed by brain CT and/or MRI in baseline conditions Cardiovascular risk factors will be evaluated for both subjects and controls on the basis of the following criteria: type 2 diabetes will be determined using a clinically based algorithm that considered age at onset, presenting weight and symptoms, family history, onset ofinsulin treatment, and history of ketoacidosis. Atrial fibrillation will be diagnosed when present on the admission ECG. Hypertension was present when a patient had received antihypertensive treatment before admission or when hypertension was diagnosed during the hospital stay by repeated detection of blood pressure ≥160/95 mmHg. Hypercholesterolemia was defined as total serum cholesterol ≥200 mg/dl or on the basis of a clinical history of hypercholesterolemia or statin treatment.
The studyIs pending of approvationby the Ethics Committee of the "Policlinico P. Giaccone" of Palermo. Written informed consent wasobtained for all patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Eligible patients were men and women over 18 years of age who had an acute ischemic stroke with a symptom time onset < 48 hours
排除标准
- •Patients with inflammatory or infectious diseases, cancer, hematological diseases and severe renal or liver failure, as well as those who were under treatment with anti-inflammatory were excluded
研究组 & 干预措施
early Atorvastatin treatment
Ischemic stroke patients treated with with atorvastatin 80 mg at admission until discharge
干预措施: Atorvastatin (Drug)
结局指标
主要结局
differences in msRankin score
时间窗: 72 hours
NIHSS score at 72 hour
时间窗: 72 hours
differences with regard of NIHSS score at 72 hours
次要结局
- Plasma levels of inflammatory cytokines at 72 hours(72 hours)
- Outcome measure ( rankin score)(seven days)
研究者
Antonino Tuttolomondo
Assistant Professor
University of Palermo