不同剂量的阿托伐他汀钙对颅内动脉重度狭窄或闭塞的缺血性脑血管病患者的临床观察

发布时间：2018-04-01 12:29

本文选题：缺血性脑血管病　切入点：阿托伐他汀钙　出处：《河北医科大学》2014年硕士论文

【摘要】：目的：脑血管病是世界范围内严重威胁人类生命和健康的主要疾病之一，它有较高的发病率和死亡率，往往会导致偏瘫、失语等严重的后遗症，并且随着年龄的增长，脑卒中的风险也在逐渐的升高，虽然给予其积极的治疗，脑卒中的复发率仍然很高，因此预防脑卒中复发具有很重要的现实意义。引起脑卒中的原因很多，颅内动脉粥样硬化性狭窄（intracranialatherosclerotic stenosis, IAS）是导致缺血性脑血管病（ischemiccerebrovascular disease, ICVD）的一个重要因素，而IAS的自然病程呈进展性以及多部位损害的特点，并且有很高的临床复发风险，因此，预防动脉粥样硬化斑块的进展可能会减少脑血管病的复发。 IAS常见的危险因素有：年龄、性别、吸烟、糖尿病、高血压和高脂血症等，其治疗方法包括内科治疗、外科治疗和血管内治疗；IAS的内科治疗包括抗栓药、调脂治疗以及控制危险因素。他汀类药物属于3-羟甲基3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂，它能够有效降低血浆甘油三脂（TG）、总胆固醇（TC）、低密度脂蛋白（LDL）的水平，并且还能使高密度脂蛋白（HDL）轻度升高。目前研究已证实阿托伐他汀钙不但能够降低血脂，还具有抗炎、改善血管内皮功能、稳定斑块等作用。一些影像学试验表明，他汀类药物可以稳定甚至逆转颈动脉及冠脉粥样硬化，从而减少心脑血管事件的风险。本试验探讨不同剂量的阿托伐他汀钙的降脂作用，应用磁共振血管成像（magnetic resonance angiography, MRA）技术评价其对颅内动脉重度狭窄或闭塞的影响，并且观察阿托伐他汀钙预防ICVD的复发和药物的安全性。方法：选择2012年5月-2013年3月在河北医科大学第二医院神经内科住院治疗及门诊就诊的ICVD患者90例，所有患者经头颅MRA检查颅内动脉为重度狭窄或闭塞。将患者随机分为3组，每组30人，，A组采用ICVD的常规治疗方法，B组给予常规治疗+阿托伐他汀钙20mg1/晚，C组给予常规治疗+阿托伐他汀钙10mg1/晚。随访观察12个月，主要的观察指标包括治疗前后血脂水平、头颅MRA的评定。安全性指标包括肝功能、肾功能、血常规、肌酶、血糖以及观察有无不良反应（包括胃肠道症状、肌肉疼痛、感觉异常等）。结果： 1血脂水平分析：组内比较：治疗1年后，A组血浆中TC、TG、LDL、HDL浓度较治疗前无明显改变，差异无统计学意义（P0.05）；B组、C组与治疗前比较均能明显降低血浆中TC、TG、LDL浓度，差异有统计学意义（P0.05），而HDL较治疗前无明显改变（P0.05）。组间比较：治疗前三组之间血浆中TC、TG、LDL、HDL浓度无明显差异（P0.05）；治疗1年后，三组间TC、TG、LDL浓度差异有统计学意义（P0.05），而HDL浓度无明显差异（P0.05），然后进行两两比较，与A组比较，B组、C组TC、TG、LDL浓度显著下降，差异均有统计学意义（P0.05），B组、C组之间TC、TG、LDL浓度差异无统计学意义（P0.05）。 2头颅MRA结果比较：经治疗1年后，三组之间差异有统计学意义（P0.05），然后进行两两比较，调整检验水准α＇=α/3=0.0167，结果示：B组与A组、C组比较，均能明显提高IAS的好转率，差异有统计学意义（P0.0167），A组、C组治疗前后MRA结果差异无统计学意义（P0.0167）。 3ICVD复发率比较：治疗1年后，A组、B组、C组发生ICVD的比率分别为24.1%、0、3.6%，三组之间ICVD的复发率差异有统计学意义（P0.05），然后三组间进行两两比较，调整检验水准α＇=α/(3+1)=0.0125，结果示：B组、C组分别与A组比较，ICVD的复发率均明显降低，差异有统计学意义（P0.0125），但B组与C组比较ICVD复发率无明显差异（P0.0125）。 4药物安全性评价： A组、B组、C组不良事件的发生率分别为6.9%、16.7%、10.3%，其中1例因转氨酶升高3倍、1例因肌酶升高5倍、1例因胃不耐受而退出试验，三组之间不良事件发生率差异无统计学意义（P0.05）。结论：对伴有IAS的缺血性脑血管病患者，长期口服阿托伐他汀钙能够有效降低患者的血脂水平，预防缺血性脑血管病的复发，而药物不良反应率并未明显增加，并且口服阿托伐他汀钙20mg能够阻止颅内动脉粥样硬化的进展甚至逆转斑块，可在临床治疗中推广应用。
[Abstract]:Objective : The cerebrovascular disease is one of the major diseases threatening human life and health . It has high morbidity and mortality , which often leads to severe sequelae such as hemiplegia , aphasia , etc .

Common risk factors for IAS include age , sex , smoking , diabetes , hypertension , and hyperlipidemia , and their therapeutic methods include internal treatment , surgical treatment , and endovascular treatment ;
This study has shown that atorvastatin calcium can stabilize and even reverse carotid artery and coronary atherosclerosis , reduce the risk of cardiovascular and cerebrovascular events , and observe the effects of atorvastatin calcium on the severity of severe stenosis or occlusion of intracranial arteries .

Methods : From May 2012 to March 2013 , 90 patients with ICVD were randomly divided into 3 groups . All patients were randomly divided into 3 groups , 30 in each group , 30 in group A and 10 mg1 / evening of atorvastatin calcium . The main observation indexes included liver function , renal function , blood routine , muscle enzyme , blood sugar and observed adverse reactions ( including gastrointestinal symptoms , muscle pain , sensory abnormality , etc . ) .

Results :

1 . Analysis of blood lipid level :

The levels of TC , TG , LDL and HDL in plasma of group A were significantly lower than those before treatment ( P0.05 ) .
The levels of TC , TG , LDL in plasma were significantly lower than those in group B and group C ( P0.05 ) .

There was no significant difference in TC , TG , LDL and HDL in plasma between the three groups before treatment ( P0.05 ) .
After 1 year of treatment , the difference of TC , TG and LDL in the three groups was significant ( P0.05 ) , but there was no significant difference in HDL concentration ( P0.05 ) .

2 Head MRA Results Comparison :

After 1 year of treatment , there was a significant difference between the three groups ( P0.05 ) , and then two comparisons were performed to adjust the test level 伪 ' = 伪 / 3 = 0.0167 . The results showed that the improvement rate of IAS was significantly improved compared with group A and C in group B ( P0.05 ) .

3ICVD recurrence rate comparison :

The rates of ICVD in group A , group B and group C were 24.1 % , 0 , 3.6 % , respectively . There was significant difference in the recurrence rate of ICVD between three groups ( P0.05 ) . The results showed that the recurrence rate of ICVD decreased significantly in group B and group C ( P 0 . 0125 ) , but there was no significant difference between group B and group C ( P 0 . 0125 ) .

4 Drug Safety Evaluation :

The incidence of adverse events in group A , group B and group C was 6.9 % , 16.7 % and 10.3 % , respectively , among which 1 case was 3 times higher because of transaminase , 1 case was due to 5 times increase of myeloperoxidase , 1 case withdrew from the test due to gastric intolerance , and there was no significant difference in the incidence of adverse events between the three groups ( P0.05 ) .

Conclusion : For patients with ischemic cerebrovascular disease with IAS , the long - term oral atorvastatin calcium can effectively reduce the blood lipid level of patients , prevent the recurrence of ischemic cerebrovascular disease , and the rate of adverse drug reaction does not increase obviously , and the oral atorvastatin calcium 20mg can prevent the progression of intracranial atherosclerosis and even reverse the plaque , and can be popularized and applied in clinical treatment .

【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R743

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