养心氏片治疗冠心病慢性心力衰竭气虚血瘀证的临床研究

【作者】 张为；

【导师】 鲁卫星；

【作者基本信息】 北京中医药大学 ， 中西医结合临床心血管， 2007， 博士

【摘要】 心力衰竭(心衰)是指任何原因造成的心肌损伤,使心肌结构和功能发生改变,导致心室泵血功能降低而引起的复杂的临床综合征,是各种心脏病的终末阶段。心力衰竭以其发病率高、患病率高、致死率高、致残率高,花费大、危害严重而成为世界性卫生健康的难题,对其研究引起了世界性的重视。目前,流行病学调查发现:冠心病是导致心力衰竭的第一位病因.20世纪90年代中期以后,对“心肌重塑是心衰发生、发展机制”的认识逐步深入,人们认识到神经内分泌模式在心力衰竭的发生、发展中起到重要作用,阻断促进心肌重构因子,阻止甚至逆转心室重构是治疗HF并降低其病死率最有效的途径,也是开发新药的靶点。应用神经内分泌拮抗剂如:血管紧张素转换酶抑制剂(ACEI)、β-受体阻滞剂、醛固酮拮抗剂和血管紧张素受体拮抗剂(ARB)等治疗,临床中成功地降低心衰死亡率和病残率,延缓了病情的发展。尽管如此,HF的高病死率和进展性特点提示:当今理想的药物治疗并未完全阻断其病理机制。西药的一些毒副作用也限制了他们在临床中的应用。中医药在防治心力衰竭方面有着悠久的历史和独特的疗效,历代医家积累了许多宝贵经验,特别是在改善症状、提高生活质量、防止病情反复方面,显示着良好的疗效。中医药的现代研究表明:中药及其组成方剂具有药理作用的多靶点效应。在拮抗神经内分泌的过度激活,防止心室重塑方面,有着很好的疗效。然而,由于缺乏严格的对照临床实验设计的支持,目前临床应用的能够替代西药改变心衰预后的中成药并不多。开发具有综合疗效,能改变心衰预后,而又价格低廉的治疗冠心病心力衰竭的中成药,对于满足日益增多的冠心病心力衰竭患者的需要,缓解我国医疗经济资源相对不足的现状,具有重要的意义。多数医家认为气虚血瘀是心力衰竭的常见证侯,常见于心衰的早期,益气温阳、活血化瘀是治疗心力衰竭的常用方法之一。养心氏片是临床中治疗冠心病心绞痛的有效药物,具有扶正固本,温阳益气,活血化瘀的作用,切合心衰的病机。为探讨其在冠心病慢性心力衰竭治疗中的临床疗效,探讨其对冠心病慢性心力衰竭患者预后的影响。我们采用分层随机、多中心、阳性药平行对照的临床研究方法,以北京中医药大学东直门医院、中国中医研究院广安门医院、首都医科大学北京中医医院就诊的患者为研究对象,以洛汀新和倍他乐克为阳性对照,对养心氏片治疗冠心病慢性心力衰竭的疗效和不良反应进行对比评价。本研究共纳入冠心病慢性心力衰竭气虚血瘀证患者77例,随机分成实验组39例和对照组38例,两组患者在入组时年龄、性别、病程、病情等一般性资料方面均无显著性差异。经过4周治疗观察,结果表明:中医证侯总疗效、心功能(NYHA分级标准)疗效、6分钟步行试验总体疗效、地高辛停减率、双氢克尿塞停减率等方面,试验组总有效率分别为84.62%、74.4%、76.9%、26.92%、29.17%,对照组总有效率为76.32%、73.7%、76.3%、21.43%、23.08%,无统计学意义(P>0.05);但在中医疗效总积分定量指标的比较中,经统计学分析,P<0.05,有统计学差异,试验组优于对照组;心悸、气短及胸闷症状的改善方面,治疗第7天,两组组间比较,P<0.01,差异有显著意义,试验组优于对照组,但在治疗第14天、第21天、第28天后两组比较,P均>0.05,无显著性差异,然而,试验过程中,试验组无加重的病例,对照组有加重的病例;在乏力、自汗、面色晦暗及舌象症状的疗效方面,治疗28天后,两组组间比较,有统计学意义,P均<0.05,试验组优于对照组;在脉象的改善方面,28天后,两组组间比较,没有显著性差异(P>0.05);两组患者均可降低升高的血清脑钠肽水平,经组间比较,无显著性差异(P>0.05)。在对心率、血压的影响方面试验组不及对照组,也有降低收缩压的作用。两组患者治疗前后对超声心动图各指标的影响方面:两组治疗后LVEF、FS、E峰、A峰、E/A等超声心动图指标与疗前自身比较,LVEF、FS、E峰、E/A有增高的趋势,A峰有降低的趋势,但经统计学分析,P均>0.05,差异无显著意义。在不良反应方面,试验组1例出现恶心、腹胀,1例出现口微干,均不影响继续服药,未见严重不良反应;对照组1例服药1周后,出现剧烈干咳,退出临床试验,2例服药后出现恶心,疲乏,洛汀新减量应用后,上症消失。2例出现窦性心动过缓,感觉轻微头晕,倍他乐克减量应用后上症消失。上述研究结果表明:养心氏片在治疗冠心病慢性心力衰竭气虚血瘀证在改善患者的心功能的疗效方面与西药洛汀新与倍他乐克的联合用药的疗效相当,在乏力、自汗、面色晦暗、舌象等单项中医证侯改善方面是它的优势,且没有使心衰患者的临床症状加重的副作用,不良反应轻微,患者能够很好的耐受;能够降低冠心病慢性心力衰竭患者增高的血清脑钠肽水平,在改善心衰患者的预后方面可能具有较好的作用,值得进一步研究开发。本实验也表明扶正固本,温阳益气,活血化瘀是治疗冠心病慢性心力衰竭的有效治疗方法。更多还原

【Abstract】 Heart failure is caused by any reasons which bring aboutmyocardial damage and change the structure and function of theheart，as a result lead to the function of ventricle pumping bloodreducing which brings about a complex clinical syndrome. Heartfailure is the final stage of every heart disease. The incidence,morbidity rate, mortality and mayhem rate of heart failure is veryhigh. The money expended on it is very large. It hazards seriously.Now it is becoming a difficult problem of sanitation and healthall of world. The study on it is think much of by the world. Atpresent, it is found out by epidemiological investigation thatcoronary heart disease is the first pathogenic factor of HF.What remolding of myocardium is the reason of generation anddevelopment of heart failure is being recognized thoroughly afterthe middle period of 1990’.people have a cognizance that the moldof nerve and endocrine takes important function on the generationand development of HF, blockading factors which forward myocardialremolding, preventing and backing the restructure of ventricle isthe most efficient path of treating HF and decreasing themortality rate of HF, and that is the target of exploiting new drug.Treating HF with antagonist of never and endocrine such as:angiotensin converting enzyme inhibitor(ACEI), beta blocker(βB),aldosterone antagonist (ALDA)，angiotensin receptor blocker(ARB)has decreased mortality and mayhem rate of HF successfully and haspostponed the development of HF.However the high mortality and progressively feature of HF cuesthat the ideal medication of today can’t shut off it’spathological mechanism. Some toxic and side effects of westernmedicine limit it application in clinical.Prevention and cure HF with Traditional Chinese Medicine iscenturies-old history and has particular curative effect, doctorsthrough the ages have accumulated a great deal of preciousexperience particularly on improving symptom, enhancing quality oflife, preventing recurrence of this disease. It has shown forth well curative effect. Modern studies on Chinese traditionalmedicine manifest that Chinese medicine and set prescription havemulti-target effect of pharmacological action. They have wellcurative effect on preventing nerve and endocrine excessivelyactivated and holding back remolding of ventricle. But for thelack of supporting by strict contrast clinical experiment Chinesepatent medicines those can take the place of west medicinechanging the prognosis of HF is very few. Exploiting low priceChinese patent medicine treating coronary heart disease chronicheart failure and changing its prognosis with multi syntheticcurative effects is very important in satisfying increasing needof patients need with CHDHF. And it is also important in relievingthe reality of relative inadequate of medical economical resources.Many doctors recognize that deficiency of Qi and blood stasisis frequently found in heart failure, especially in early stage ofHF. Correspondingly invigorating Qi and warming Yang, promotingblood circulation to dispel blood stasis is often used in treatingpatients who suffer from HF. YangXinShiPian is an efficientmedicine treating CHD angina pectoris in clinic practice. It hassuch functions as strengthening the body resistance, invigoratingQi and warming Yang, promoting blood circulation to dispel bloodstasis which accord with the pathogenesis of HF.To disclose the clinical influnce and the prognostic influenceof YangXinShiPian on patients with Qi deficiency blood stagnationsyndrome and chronic heart failure caused by coronary heartdisease,we studied this thesis adopting stratified random, multicenter,positive medicine parallel contrast clinical researchmethod, using the patients who visit cardio and vessel section ofDongZhiMen hospital which affiliated Beijing TCM university,andGuangAnMen hospital which affiliated China TCM Academy and BeijingTCM hospital which affiliated Capital Medicine university ,contrasting with LOTINSIN and BETALOC as the positive medicine.We inspired 77 patients who suffered from CHF caused by CHDbelong to qi deficiency and blood stasis syndrome. They wererandomly divided into 2 groups. One was test group with 39patients. The other was control group with 38 patients. Betweentwo groups there was no significant difference in age, sex, courseof diseases and severity degree before therapy. After 4 weeks treatment, clinical curative effects show: there is no remarkabledifference in following aspects as general curative effect of TCMSyndromes, cardiac function curative effect (NYHA gradingstandards), 6-minute-walk trail general curative effect, thestopping and decreasing rate of DIGOXIN, the stopping anddecreasing rate of HYDRODIURIL after statistics analysis（p>0.05）.But making a comparison between 2 groups in general integral ofTCM Syndromes, there is remarkable difference after statisticsanalysis (P<0.05). The test group is better than the contrastgroup. In the contrast of main TCM symptom, we can see that Thetest group is better than the contrast group after 7 daystreatment in the following aspects: palpitation, short breath,chest stuffiness. But there is no remarkable difference after 14,21, 28 days treatment (P>0.05), however there is aggravatingpatients in the contrast group; on the contrary, none, in testgroup. There is statistical difference after 28 days treatmentbetween the two groups in the following aspects: asthenia,sweating, darkish complexion and picture of tongue (P<0.05). Thetest group is better than the contrast group. There is nostatistical difference after 28 days treatment between the twogroups in pulse condition（P>0.05）. The two groups can decrease theraising level of blood serum BNP all. There is no statisticaldifference after 28 days treatment between the twogroups（P>0.05）.The contrast group is better than the test group indecreasing heart rate and blood pressure, however the test groupcan decrease systolic pressure too. There is no statisticaldifference by contrast their echocardiogram index (LVEF, FS, Epeak, A peak, E/A) before and after therapy (P>0.05), althoughLVEF, FS, E peak and E/A of the two groups manifest increasingtrend, A peak of the two groups manifest decreasing trend. Inadverse reaction aspect, 1 patient of the test group appearssickness and abdominal distention. 1 patient of the test groupappears slight dry mouth, these can’t affect on their continuingtaking medicine. We can’t find severe adverse reactions; In thecontrast group, 1 patient appears acutely dry cough after takingmedicine 1 week and he quit this clinical trail, 2 patients appearsickness and fatigue and disappear after reducing the dose ofLOTINSIN, 2 patients appear sinus bradycardia and slight dizziness and disappear after reducing the dose of BETALOC.The above findings demonstrate: using YangXinShiPian treatingpatients who suffer from CHDCHF belong to Qi deficiency and bloodstasis syndrome is as curative as using west medicine combinationof BETALOC and LOTINSIN on the aspect of heart functionimprovement. The improvement of single TCM symptom such as fatigue,sweating, darkish complexion and tongue picture YangXinShiPian issuperiority. it has no the side effect of aggravating the symptomof HF. Few adverse reaction, can be well tolerated. It candecrease the raising level of serum BNP in patient who suffer fromHF. Maybe, it is a good medicine on improving the prognosis ofpatients who suffer from HF. It is worth studying more. This studyalso demonstrates that it is an efficient therapeutic methods ofstrengthening the body resistance, invigorating Qi and warmingYang, promoting blood circulation to dispel blood stasis.更多还原