【作者】 李勇；

【导师】 周晓芳；

【作者基本信息】 遵义医学院 ， 内科学（心血管内科）（专业学位）， 2016， 硕士

【摘要】 研究背景:高血压作为最常见的慢性病之一,特别是在我国,人口基数大,高血压发病率尤为高。高血压与心血管疾病等的发生风险紧密相关。降低血压能够减少脑卒中、心血管事件的发生,改善生存治疗,减轻生活负担等诸多获益。随着我国老龄化的进程,老年高血压的发病率、致残率、致死率急速增加,给家庭乃至给社会带来了重大经济负担。加之我国老年高血压患者人口众多,老年高血压不容忽视,可以说老年高血压既是医学问题,更是社会问题。β受体阻滞剂,多用于心律失常、心力衰竭、冠心病、心肌病等领域,起到控制心率,减少心血管事件,保护靶器官作用,其降血压作用并不被重视。但这个曾经抗高血压治疗中经典的一线心血管药物,近年来却不断引来争议。是否将这一类药在高血压治疗一线药物中剔除?一时间,β受体阻滞剂的地位成为一个备受争议的话题。大量文献也指出:与其他降压药物相比,β受体阻滞剂组心血管事件更多,老年高血压患者容易心动过缓,故获益更少,而且预防卒中、降低死亡率略差,能增加糖尿病发病风险等。但大多数临床试验都基于阿替洛尔得来,但众所周知,阿替洛尔为短效水溶性β受体阻滞剂,不能完全代表其他β受体阻滞剂,笔者选取目前临床中使用量较大的美托洛尔,来研究美托洛尔对于老年高血压的患者在降压、保护靶器官和不良反应的与其他类降压药及同类β受体阻滞剂比较,用meta分析的方法评价美托洛尔能否使老年高血压患者获益,在临床用药中起到指导作用。研究目的:用meta分析的方法评价美托洛尔与其他药物,其他药物包含其他类降压药(血管紧张素转化酶抑制剂、血管紧张素II受体拮抗剂、钙离子通道拮抗剂、利尿剂)及同类β受体阻滞剂(比索洛尔、阿替洛尔、卡维地洛等)在老年高血压治疗中对降低收缩压、降低舒张压;控制心率;影响糖脂代谢及不良反应等方面的异同,从而评价美托洛尔在老年高血压治疗中的地位,进而指导临床实践中老年高血压治疗的用药。研究方法:计算机检索The Cochrane Library、Medline、Ebsco、Pubmed、EMbase,CNKI,维普,中国生物医学文献服务系统和万方,收集2000年1月至2015年12月关于美托洛尔与其他类降压药,美托洛尔与同类β受体阻滞剂在治疗老年高血压疗效的文献。根据预先制定的筛选条件筛选文献。提取关于治疗情况,治疗前后收缩压、舒张压,治疗前后心率,不良反应人数,退出试验人数,空腹血糖,治疗前后血脂变化等资料,并对纳入文献进行质量评价,然后用Rev Man 5.3软件进行分别对上述数据进行meta分析。研究结果:共纳入12项临床随机对照研究。共纳入患者1190人,其中美托洛尔组593人,其他药物组597人。Meta结果:1、美托洛尔在老年高血压治疗中降压作用比较中纳入11篇研究,共纳入1097人,其中美托洛尔组547人,其他药物组550人。经亚组分析结果显示:(1)降低收缩压方面:与其他类降压药物比较[MD=1.66,95%CI:0.84~2.48,P<0.0001]。与同类药物比较[MD=3.62,95%CI:2.49~4.75,P<0.00001],降低收缩压作用美托洛尔弱于其他降压药及同类β受体阻滞剂。(2)降低舒张压方面:与其他类降压药物比较[MD=0.67,95%CI:0.02~1.32,P=0.04]。与同类药物比较[MD=1.39,95%CI:0.66~2.13,P=0.0002],降低舒张压作用美托洛尔弱于其他类降压药及同类β受体阻滞剂。(3)降压有效率方面:OR=1.26,95%CI[0.78,2.01],P=0.35,差别无统计学意义。2、美托洛尔在老年高血压治疗中空腹血糖比较中纳入5篇研究,共纳入患者419人,其中美托洛尔组208人,同类β受体阻滞剂组211人。在对空腹血糖(FPG)的影响中[MD=0.02,95%CI:-0.13~0.17,P=0.81]。美托洛尔与同类β受体阻滞剂比较,不影响FPG。3、在不良反应发生的比较中将12项研究合并效应量,共纳入患者1190人,其中美托洛尔组593人,其他药物组597人。得到[OR=0.73,95%CI:0.44~1.20,P=0.22],差别无统计学意义。4、美托洛尔在老年高血压治疗中血脂比较中纳入3篇研究,共纳入186人,其中美托洛尔组92人,同类β受体阻滞剂组94人。Meta结果为:(1)美托洛尔与其他药物在老年高血压治疗中甘油三脂(TG)变化,结果[MD=0.01,95%CI-0.18~0.20,P=0.92],差别无统计学意义。(2)美托洛尔与其他药物在老年高血压治疗中总胆固醇(TC)变化,结果[MD=0.33,95%CI-0.35~0.14,P=0.10],差别无统计学意义。(3)美托洛尔与其他药物在老年高血压治疗中低密度脂蛋白(LDL-C)变化,结果[MD=-0.11,95%CI-0.35~0.14,P=0.40],差别无统计学意义。(4)美托洛尔与其他药物在老年高血压治疗中高密度脂蛋白(HDL-C)变化,结果[MD=-0.02,95%CI-0.14~0.10,P=0.73],差别无统计学意义。结论:美托洛尔与其他药物在老年高血压治疗中比较,其降低压作用弱于其他类降压药及同类β受体阻滞剂,但降压效果仍较为明显,且不影响空腹血糖,脂类代谢、降压有效率与不良反应相当,故美托洛尔在治疗老年高血压作为降压药物仍有其可取之处,而至于是否可作为一线药物,本项meta分析未能得出明确的结论,仍需要临床数据进一步证明。更多还原

【Abstract】 BackgroundHypertension is one of the most common chronic disease,especially in China, our overpopulated country,the incidence of hypertension is significantly higher.Hypertension also closely associates with cardiovascular risk and events.Reducing the blood pressure can reduce stroke, cardiovascular events, and so on, improve survival treatment, reduce the burden of life, and many other benefits.Along with the aging process,the incidence, morbidity and mortality of senile hypertension increased sharply, to family and the society brings great economic burden.There is a large number of elderly hypertension,so it should not be ignored, the elderly hypertension is not only a medical problem, but also a social problem.Beta blockers, usually for arrhythmia, heart failure, cardiomyopathy,coronary heart disease, and other fields, to control the heart rate, reduce cardiovascular events and protect target organs, the anti-hypertensive effect is not valued.But once the classic line of drug of anti-hypertensive treatment, in recent years has been controversial.Will we get rid of this kind of medicine from the drugs that the first-line treatment of hypertension ?A large number of the documents also point out:Compared with other anti-hypertensive drugs, beta blockers set of events more and less benefit from the elderly patients with high blood pressure, and less benefit for preventing stroke, reducing the mortality, but also can increase the risk of diabetes and so on.Most of the clinical trials are derived based on atenolol, but it is well known as short-acting water-soluble beta-blockers, can not fully represent the other beta blockers. The author select the clinical usage of larger, metoprolol, to study the metoprolol in patients with senile hypertension in anti-hypertension, protecting target organs and adverse reactions compared with the other anti-hypertensive agents and the other drugs of same class, evaluating metoprolol can be benefit for elderly patients with high blood pressure,and provide guidelines for rational use of clinical drug. ObjectiveUse the method of meta analysis to evaluate metoprolol and other types of anti-hypertension drugs and other drugs of same class in the elderly hypertension treatment to reduce systolic blood pressure, reduce the diastolic blood pressure,adverse reactions; The impact on the heart rate; Glucolipid metabolism, etc, thus evaluation of metoprolol in treating senile hypertension.To guide the clinical practice of the treatment of elderly hypertension. MethodsWe search metoprolol and other types of anti-hypertension drugs and other drugs of same class in the elderly hypertension treatment from The Cochrane Library, MEDLINE, Ebsco, Pubmed, Embase, CNKI, VIP, sino- med and Wanfang(2000-2015/Dec),and collect the curative effect of metoprolol and other anti-hypertensive drugs, metoprolol and other drugs of same classs in the treatment of elderly hypertension. Filter the literature according to the established factors.Extraction about the treatment, before and after the treatment systolic blood pressure, diastolic blood pressure, the heart rate, the number of adverse reactions, exit the test number, fasting blood glucose,blood lipid, and the quality evaluation of the literature, and then use RevMan 5.3 for Meta-- analysis. ResultsIn this Meta-- analysis,we summarized 12 trials including 1190 subjects which 593 from metoprolol treatment group and 597 from the control group.The results showed that:1, We have 11 trials including 1097 subjects,547 from the Metoprolol group and 550 from the control group in elderly hypertension of anti-hypertensive effect.Subgroup analysis shows:(1) Reduce systolic blood pressure:Compared with other types of anti-hypertension drugs(MD=1.66,95%CI:0.84~2.48,P<0.0001).Compared with other drugs of same class(MD=3.62,95%CI:2.49~4.75,P<0.00001).Metoprolol was not superior to other drugs in reducing SBP.(2) Reduce diastolic blood pressure:Compared with other types of anti-hypertension drugs(MD=0.67,95%CI:0.02~1.32,P=0.04).Compared with other drugs of same class(MD=1.39,95%CI:0.66~2.13,P=0.0002).Metoprolol was not superior to other drugs in reducing DBP.(3)The anti-hypertensive effective rate:Compared with other types of anti-hypertension drugs(OR=1.26,95%CI:0.78~2.01,P=0.35).There was no statistical difference.2,There are 5 trials including 419 subjects,208 from the Metoprolol group and 211 from the control group in elderly hypertension of fasting blood-glucose(FBG).The result:(MD=0.02,95%CI:-0.13~0.17,P=0.81). There was no statistical difference.3, In the adverse reaction:The 12 trials,and the result is:(OR=0.73,95%CI:0.44~1.20,P=0.22).There was no statistical difference.4,In the blood lipid metabolism:There were 3 trials including 186 subjects,92 from the Metoprolol group and 94 from the control group in elderly hypertension of blood lipid metabolism.Subgroup analysis shows:(1) About Triglyceride(TG):(MD=0.01,95%CI-0.18~0.20,P=0.92).There was no statistical difference.(2) About total cholestrol(TC):(MD=0.33,95%CI-0.35~0.14,P=0.10).There was no statistical difference.(3) About low density lipoprotein cholesterol(LDL-C):(MD=-0.11,95%CI-0.35~0.14,P=0.40).There was no statistical difference.(4) About high density lipoprotein cholesterol(HDL-C):(MD=-0.02,95%CI-0.14~0.10,P=0.73).There was no statistical difference. ConclusionMetoprolol compared with other types of anti-hypertension drugs and other drugs of same class in the elderly hypertension treatment, Metoprolol was not superior to other drugs in anti-hypertensive effect,But its anti-hypertensive efficacy was still obvious,and had no affect in the fasting plasma glucose,in the blood lipid metabolism. The anti-hypertensive effective rate and the adverse reaction,there was no statistical difference from others.Therefore, metoprolol in the treatment of elderly hypertension whether can be used as first-line drugs, this meta-analysis did not draw a clear conclusion, the clinical data should have been needed for further proofing.更多还原