急性心肌梗死中西医结合优化治疗方案的构建和评价研究
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摘要
研究背景：
急性心肌梗死(acute myocardial infarction, AMI)是严重危害人类健康的心血管疾病,在发达国家被称为“头号杀手”,是世界范围的主要死亡原因。在我国,本病不如欧美多见,但近年来的发病呈逐年增长趋势。AMI也给社会和家庭带来了沉重的医疗费用负担,我国AMI住院费用据各种疾病之首。AMI发病率和医疗费用的增加给个人、家庭和社会带来沉重的负担,提高AMI的防治水平,控制其医疗费用,成为心血管领域和卫生管理领域一个重要的课题。
广东省中医院于1997年在全国中医系统最早开展冠心病介入治疗技术研究,在导师陈可冀院士活血化瘀理论和邓铁涛教授“心脾相关”学术思想的指导下,将冠心病介入治疗纳入中医辨证诊疗体系,提出冠心病介入术后患者以气虚血瘀为主要病机,确立益气活血法为冠心病介入术后的主要治法,在此治法指导下开展益气活血法用于冠心病介入治疗术后的基础和临床研究,取得良好的临床疗效。
研究目的：
本研究在既往研究成果的基础上,通过证候调查、文献研究和专家咨询,结合名老中医学术思想,制定AMI中西医结合优化诊疗方案,通过临床对照研究,进行方案的有效性和医疗费用评价,为AMI中西医结合临床路径的制定奠定基础。
研究内容与方法：
1运用临床流行病学方法,制定《急性心肌梗死围再灌注治疗期中医证候信息采集表》,观察AMI围再灌注治疗期中医证候变化规律,通过聚类分析探索AMI的证候要素组合规律,通过Logistic回归分析证候的可能影响因素；
2在整合、优化既往研究成果基础上,采用循证医学方法进行文献调研,运用德尔菲评价法进行专家咨询调研,初步建立AMI中西医结合优化诊疗方案；
3运用临床流行病学／DME方法,进行回顾性和前瞻性对照研究,对AMI中西医结合优化治疗方案的有效性进行评估。
研究结果：
1 AMI围再灌注治疗期的中医证候要素分布及变化规律研究
1.1证候要素分布：AMI再灌注治疗前和治疗后第3日证候要素频次对比,气虚证、痰热证较前增多,血瘀证、痰寒证较前减少,差异具有统计学意义(P<0.05)；阳虚证、阴虚证较前增多,寒凝证、气滞证较前减少,但差异均无统计学意义(P>0.05)。
1.2证候要素聚类分析：再灌注治疗后,如果聚成3类,则气虚、血瘀为一类,痰寒自成一类,其余证候为一类。
1.3证候要素的影响因素回归分析：气虚证可能的影响因素是左室射血分数(EF)[OR=0.90,95%CI(0.84-0.97)],阴虚证的影响因素有糖尿病[OR=9.0×109,95%CI(0.00-∞)]和空腹血糖[OR=1.39×109,95%CI(1.01-1.90)],阳虚证的影响因素为肾功能不全[OR=238.45,95%CI(1.13-1304.11)]和EF[OR=0.81,95%CI(0.71-0.91)],痰热证的影响因素为吸烟[OR=10.00,95%CI(1.15-86.88)]和高脂血症[OR=4.0×109,95%CI(0.00-∞)],寒凝证的影响因素为心律失常[OR=2.70,95%CI(0.94-7.75)]和肾功能不全[OR=68.02,95%CI(1.31-3524.48)],气滞证的影响因素有年龄分段[OR=0.24,95%CI(0.07-0.80)]。
2 AMI中西医优化治疗方案的专家咨询
2.1第一轮专家咨询
共发出问卷10份,收回10份,专家积极系数为100%；AMI的基本证侯要素方面,专家选择频次排列如下：血瘀>气虚>痰浊>阴虚>阳虚>寒凝>气滞。辨证治疗方面,主要证候的选择频次排列如下：气虚血瘀>气虚痰瘀>痰浊痹阻>瘀血闭阻>寒凝心脉>气阴两虚>心阳不振。再灌注治疗后,中医主要治法的选择依次为活血>益气>化痰>温阳>养阴>祛寒>清热解毒。中医治疗干预途径选择频次依次为静脉滴注中成药>口服中成药>口服汤药,所有专家不认可针灸对AMI的治疗效果。
2.2第二轮专家咨询
共发出问卷10份,共收回10份,专家积极系数为100%；所有专家均认可“血瘀证是AMI的基本证候要素”、“气虚证是AMI的基本证候要素”；多数专家认可,对于急性心肌梗死采取新的简化辨证方案“气虚血瘀证为基本证型,痰浊证、阴虚证、阳虚证是主要的证候要素,通过基本证型和单个、多个主要证候要素的结合,覆盖本病的主要证型”,AMI再灌注治疗后,制定病证结合的优化治疗方案,基本治法为益气活血化瘀；兼证治法：通阳化痰(寒痰)或清热化痰(热痰)、养阴、温阳。
3 AMI中西医结合治疗方案的有效性评价
2006年1月-2009年12月纳入符合标准的患者218例(治疗组为152例,对照组66例),治疗组予以益气活血为主中西医结合优化治疗方案,对照组以活血化瘀为主的旧方案,两组的基线资料对比,性别、年龄、梗死类型、梗死部位、泵功能、冠心病危险因素、梗死相关靶血管、病变部位、冠脉病变评分(Gensini评分)、再灌注治疗方式、心功能指标、心肌酶学和血脂指标等方面比较,差异无统计学意义(P>0.05),具有可比性。
3.1住院时间
治疗组的平均住院时间为8.13±4.52天,对照组为10.36±6.77天,两组住院时间比较差异有统计学意义(P<0.05)。按照泵功能的不同进行亚组分析,两组泵功能Ⅰ级、Ⅳ级的AMI患者平均住院时间比较,差异有统计学意义(P<0.05),治疗组的泵功能Ⅰ级、Ⅳ级者平均住院时间相对较对照组短。
3.2住院费用
治疗组的平均住院费用为48570.69±18982.81元,对照组为56706.27±28232.13元,两组住院费用比较,差异有统计学意义(P<0.01)。按照泵功能的不同进行亚组分析,泵功能Ⅰ级两组的平均住院总费用比较,差异有统计学意义(P＜0.05),治疗组的泵功能Ⅰ级者平均住院总费用相对较对照组少。3.3气虚症状记分和血瘀症状积分的比较
气虚症状记分的重复测量方差分析,模型差异有统计学意义(P=287.90,P=0.000),经校正协变量后,两组气虚症状记分比较,差异有统计学意义(P<0.01),治疗组气虚症状记分低于对照组。
血瘀症状记分的重复测量方差分析,模型差异有统计学意义(P=54.18,P=-0.000),经校正协变量后,两组血瘀症状记分比较,差异无统计学意义(P>0.05)。3.4住院期间主要心血管事件发生的比较
主要心血管事件(major adverse cardiac events, MACE)定义为死亡、非致死性再次心肌梗死、靶血管血运重建、中风。住院期间,治疗组死亡9例,靶血管血运重建3例；对照组死亡3例,靶血管血运重建2例,两组MACE发生比较,差异无统计学意义(P>0.05)。3.5预测主要心血管事件发生的因子分析
影响MACE发生因子的Logistics回归分析显示,术前血瘀症记分[OR=1.13,P<0.01,95%CI(1.031,1.237)]、泵功能分级[OR=4.94,P<0.001,95%CI(2.69,9.07)]是预测MACE发生与否的重要因子,血瘀症状记分值>25较血瘀症状记分值≤25的患者院内MACE发生的比值比为2.2。
研究结论：
1围再灌注期的中医证候要素变化规律研究显示,再灌注治疗具有活血、化痰的祛邪作用,再灌注治疗后气虚证成为主要矛盾,气虚血瘀证为再灌注治疗后的主要证候。
2专家共识认为,气虚血瘀证为AMI的基本证型,痰浊证、阴虚证、阳虚证是重要的证候要素,通过基本证型和单个或多个证侯要素的结合,覆盖AMI主要证型。AMI再灌注治疗后,基本治法为益气活血化瘀,补充治法为通阳化痰或清热化痰、养阴、温阳。
3临床对照试验发现,以益气活血为主的AMI中西结合优化治疗方案可降低患者住院时间和住院费用,并有效改善患者的气虚症状。
4血瘀症状记分值>25分和心源性休克可能是AMI患者院内发生心血管事件的主要预测因子。
Background:
Acute myocardial infarction (AMI), a cardiovascular disease, being named "the first killer" in the developed country and the leading cause of mortality cause in global countries, severely damage human health.. Although the incidence of AMI in Chinese is lower than it in Europe or America, the incidence had a rapid growth tendency during the past decades. And the increase of AMI incidence lay serious burden of medical cost on the shoulder of individuals, families and society. To improve the prevention and cure of AMI and to control its medical cost has become a hot research topic in the field of cardiovascular disease and health supervision.
Guangdong Provincial Hospital of Chinese Medicine firstly carried out Percutaneous coronary intervention(PCI) in the national-wide Chinese Medicine(CM) system in 1997 and proposed the theory that PCI was classified into CM clinic system and Qi-deficiency and blood-stasis was the main pathogenesis in patients with coronary heart disease after PCI, establishing benefiting qi and promoting blood circulation as the main treatment after PCI, under the guidance of the theory of blood-activating and stasis-resolving and academic thought of'heart and spleen-related'. This treatment program has been widely used in management of patients after PCI in the field of basic and clinical research and achieved a better clinical effect.
Purpose:
To construct and evaluate the efficacy of optimized management of integrated Chinese and Western Medicine for patients with AMI by the way of syndrome surveys, literature research and expert consultation, combining with the distinguished Chinese academic thought and based on previous research results, which provide a basis for the form to the AMI clinical pathway with integrated Chinese and Western Medicine. Subject and methods:
1 Syndrome Information Collection in Patients with AMI around the Reperfusion Treatment Period Form was formulated to observe the characteristic symptoms and the rules of evolvements for AMI in the perio-reperfusion by the clinical epidemiology and explore the combination rules of AMI syndrome elements by cluster analysis, meanwhile, possible influencing factors were explored by Logistic regression analysis.
2 Based on the integration and optimization of previous research results, optimized management of Integrated Chinese and Western Medicine for patients with AMI was initially established through literature research with evidence-based medicine method and expert consultation with delphi evaluation.
3 The efficacy of the optimized management of Integrated Chinese and Western Medicine for patients with AMI was evaluated by retrospective and prospective controlled study according to clinical epidemiology or DME approach.
Results:
1 Study on the law of distribution and evolvement of syndrome elements during peri-reperfusion period
1.1 Distribution and evolvement of syndrome elements There were significant differences in the frequency of syndrome elements of qi-deficiency, blood-stasis phlegm-heat and phlegm-cold between the third day after reperfusion and before (P<0.05); However, there were no statistic difference in the frequency of yang-deficiency, yin-deficiency, cold-coagulation and qi-stagnation (P>0.05).
1.2 Clustering analysis of syndrome elements If syndrome elements of patients after reperfusion were clustered into three categories, one was qi-deficiency and blood-stasis, the other is phlegm-cold with other syndromes as the remaining.
1.3 Regression analysis of the impact factors of syndrome elements Regression analysis of the impact factors of syndrome elements revealed that: the impact factor of qi-deficiency syndrome was left ventricular ejection fraction (EF) [OR=0.90,95%CI (0.84-0.97)] and impact factors of yin-deficiency syndrome were diabetes [OR=90×109,95%CI(0.00-∞)] and fasting blood glucose[OR=1.39×109,95%CI (1.01-1.90)], with renal dysfunction [OR= 238.45,95%CI (1.13-1304.11)] and EF [OR=0.81,95%CI (0.71-0.91)] for yang-deficiency syndrome, smoking [OR=10.00,95%CI (1.15-86.88)] and hyperlipidemia[OR=4.0×109,95%CI(0.00-∞)] for phlegm-heat syndrome, arrhythmias [OR=2.70,95%CI(0.94-7.75)] and renal dysfunction [OR= 68.02,95%CI (1.31-3524.48)] for cold-coagulation syndrome, age [OR=0.24,95%CI (0.07-0.80)] for qi-stagnation syndrome.
2 Study of expert consultation concerning optimized management of integrated Chinese and Western Medicine for patients with AMI.
2.1 The first round of expert consultation A total of 10 questionnaires were mailed and returned, therefore, the positive coefficient of experts were 100%. With regard to the basic syndrome elements of AMI, the frequency selected by the experts ranked as follows:blood-stasis > qi-deficiency> phlegm-turbidity> yin-deficiency, yang-deficiency> cold-coagulation>qi-stagnation. Regarding to the main Chinese syndromes of AMI based on the differential syndrome treatment, the frequency selected by the experts ranked as follows:qi-deficiency and blood-stasis>qi-deficiency and phlegm-blood-stasis>blockage of phlegm>blood-stasis>cold-coagulation > qi-yin-deficiency> heart-yang-deficiency. The choice of primary CM treatment pattern for patients after reperfusion therapy sorted as follows: activating blood>enforcing Qi>diffusing phlegm>warming yang>enriching Yin>dispersing cold> clearing heat and removing toxin. Lastly, all the experts did not endorse the therapeutic efficacy of acupuncture on patients with AMI.
2.2 The second round of expert consultation Similarly, a sum of 10 questionnaires were mailed and returned, therefore, the positive coefficient of experts were 100%. All the experts approved "Blood-stasis syndrome is a basic syndrome element of AMI," "Qi-deficiency syndrome is also the basic one". Most of the experts adopted a new simplified differential syndrome program for AMI:Qi-deficiency and blood-stasis is the basic syndrome with phlegm-turbidity, yin-deficiency and yang-deficiency as the main syndrome elements, covering the majority of CM syndromes of AMI by differential combination of the basic syndrome with a single or more syndrome elements and recognized optimized management of integrated Chinese and Western Medicine for patients with AMI after reperfusion therapy:the basic treatment method is to benefit qi and promote blood circulation with the supplemental therapy of minor elements such as activating yang and diffusing phlegm or removing heat-phlegm, enriching yin and warming yang.
3 Evaluation of the efficacy of management of integrated Chinese and Western Medicine for patients with AMI 218 cases of AMI patients were included based on the inclusion criteria, among which the treatment group was 152 patients with 66 patients in control group. The treatment group was afforded with the optimized integrative medicine treatment based on benefiting qi and promoting blood circulation and the control group received the treatment of activating blood and resolving stasis. There was no significant difference between two groups concerning gender, age, infarction type, infarction site, pump function, risk factors of CHD, infarct-related target vessel, location of lesion, coronary artery disease score (Gensini score), reperfusion therapy pattern, cardiac function, myocardial enzyme and lipid parameters. In other words, the baseline data of two groups was balanced and comparable.
3.1 Hospital stay
There was statistically significant difference between two groups in the average hospital stay (8.13±4.52 days vs.10.36±6.77days, P<0.05). In subgroup analysis, the difference of the hospital stay was statistically significant between two groups with pump function class I (P＜0.05). Therefore, compared with the control group, the average stay of the treatment group with pump function Class I was relatively short.
3.2 Hospital charges
The comparison between the treatment group and the control group in average hospital charges showed statistically significant difference (48570.69±18982.81 Yuan vs.56706.27±28232.13 Yuan, P<0.01). In subgroup analysis, there was significant statistical difference of.the average hospital costs between two groups with pump function I class (P<0.05) and the cost of treatment group was less than control group.
3.3 The syndrome score of qi-deficiency and the syndrome score of blood-stasis Repeated measures analysis of qi-deficiency syndrome score between two groups showed that model difference was significant (F=287.90, P=0.000). After correcting the covariate, there was statistically significant difference in qi-deficiency syndrome score between two groups (P<0.01) and qi-deficiency syndrome score of treatment group was lower than the control group after treatment.
Repeated measures analysis of blood-stasis syndrome score between two groups disclosed that the model difference was significant (F=54.18, P=0.000) and the difference was no statistically significant in blood-stasis syndrome score between two groups (P> 0.05) after correcting the covariate. 3.4 Major adverse cardiac events
Major adverse cardiac events (MACE) was defied as death, non-lethal re-myocardial infarction, target vessel revascularization and stroke. During hospitalization,9 patients died and 3cases of target vessel revascularization in the treatment group and 3 patients died and 2 cases of target vessel revascularization in control group. The difference of frequency of MACE between two groups was not statistically significant (P> 0.05) 3.5 Predicting factors of major adverse cardiac events
The results of logistics regression analysis of predicting factors of MACE revealed that preoperative blood stasis syndrome scores[OR= 1.13, P<0.0l,95%CI (1.031,1.237)] and the pump function classification [OR= 4.94, P<0.001,95%CI (2.69,9.07)] were important factors impacting MACE events and the ratio of the frequency of MACE in patients whose blood-stasis syndrome scores> 25 to the that of MACE in patients whose blood-stasis syndrome scores≤25 was 2.2.
Conclusions:
1 The Study on the regularity of distribution and evolvements of syndrome elements during peri-reperfusion period shows that reperfusion therapy plays a role of activating blood and diffusing phlegm in terms of CM theory and Qi-deficiency and blood-stasis develop to the major syndrome after reperfusion
therapy.
2 Expert consultation and consensus conclude that qi-deficiency and blood-stasis is the basic syndrome type with phlegm-turbidity, yin-deficiency and yang-deficiency as the main syndrome elements, which covers the majority of CM syndromes of AMI by differential combination of the basic syndrome with a single or more syndrome elements and optimized management of integrated Chinese and Western Medicine for patients with AMI after reperfusion therapy is that the basic treatment method is to benefit qi and promote blood circulation with the supplemental therapy of syndrome element such as activating yang and diffusing phlegm or removing heat-phlegm, nourishing yin and warming yang.
3 The results of clinical controlled trials reveal that the optimized management of integrated Chinese and Western Medicine based on benefiting qi and promoting blood circulation could reduce the stay of hospitalization and hospital costs of AMI patients and improve qi-deficiency symptoms.
4 Blood-stasis syndrome score>25 and cardiac shock may be the significant predictors of major adverse cardiovascular events.
急性心肌梗死(acute myocardial infarction, AMI)是严重危害人类健康的心血管疾病,在发达国家被称为“头号杀手”,是世界范围的主要死亡原因。在我国,本病不如欧美多见,但近年来的发病呈逐年增长趋势。AMI也给社会和家庭带来了沉重的医疗费用负担,我国AMI住院费用据各种疾病之首。AMI发病率和医疗费用的增加给个人、家庭和社会带来沉重的负担,提高AMI的防治水平,控制其医疗费用,成为心血管领域和卫生管理领域一个重要的课题。
广东省中医院于1997年在全国中医系统最早开展冠心病介入治疗技术研究,在导师陈可冀院士活血化瘀理论和邓铁涛教授“心脾相关”学术思想的指导下,将冠心病介入治疗纳入中医辨证诊疗体系,提出冠心病介入术后患者以气虚血瘀为主要病机,确立益气活血法为冠心病介入术后的主要治法,在此治法指导下开展益气活血法用于冠心病介入治疗术后的基础和临床研究,取得良好的临床疗效。
研究目的：
本研究在既往研究成果的基础上,通过证候调查、文献研究和专家咨询,结合名老中医学术思想,制定AMI中西医结合优化诊疗方案,通过临床对照研究,进行方案的有效性和医疗费用评价,为AMI中西医结合临床路径的制定奠定基础。
研究内容与方法：
1运用临床流行病学方法,制定《急性心肌梗死围再灌注治疗期中医证候信息采集表》,观察AMI围再灌注治疗期中医证候变化规律,通过聚类分析探索AMI的证候要素组合规律,通过Logistic回归分析证候的可能影响因素；
2在整合、优化既往研究成果基础上,采用循证医学方法进行文献调研,运用德尔菲评价法进行专家咨询调研,初步建立AMI中西医结合优化诊疗方案；
3运用临床流行病学／DME方法,进行回顾性和前瞻性对照研究,对AMI中西医结合优化治疗方案的有效性进行评估。
研究结果：
1 AMI围再灌注治疗期的中医证候要素分布及变化规律研究
1.1证候要素分布：AMI再灌注治疗前和治疗后第3日证候要素频次对比,气虚证、痰热证较前增多,血瘀证、痰寒证较前减少,差异具有统计学意义(P<0.05)；阳虚证、阴虚证较前增多,寒凝证、气滞证较前减少,但差异均无统计学意义(P>0.05)。
1.2证候要素聚类分析：再灌注治疗后,如果聚成3类,则气虚、血瘀为一类,痰寒自成一类,其余证候为一类。
1.3证候要素的影响因素回归分析：气虚证可能的影响因素是左室射血分数(EF)[OR=0.90,95%CI(0.84-0.97)],阴虚证的影响因素有糖尿病[OR=9.0×109,95%CI(0.00-∞)]和空腹血糖[OR=1.39×109,95%CI(1.01-1.90)],阳虚证的影响因素为肾功能不全[OR=238.45,95%CI(1.13-1304.11)]和EF[OR=0.81,95%CI(0.71-0.91)],痰热证的影响因素为吸烟[OR=10.00,95%CI(1.15-86.88)]和高脂血症[OR=4.0×109,95%CI(0.00-∞)],寒凝证的影响因素为心律失常[OR=2.70,95%CI(0.94-7.75)]和肾功能不全[OR=68.02,95%CI(1.31-3524.48)],气滞证的影响因素有年龄分段[OR=0.24,95%CI(0.07-0.80)]。
2 AMI中西医优化治疗方案的专家咨询
2.1第一轮专家咨询
共发出问卷10份,收回10份,专家积极系数为100%；AMI的基本证侯要素方面,专家选择频次排列如下：血瘀>气虚>痰浊>阴虚>阳虚>寒凝>气滞。辨证治疗方面,主要证候的选择频次排列如下：气虚血瘀>气虚痰瘀>痰浊痹阻>瘀血闭阻>寒凝心脉>气阴两虚>心阳不振。再灌注治疗后,中医主要治法的选择依次为活血>益气>化痰>温阳>养阴>祛寒>清热解毒。中医治疗干预途径选择频次依次为静脉滴注中成药>口服中成药>口服汤药,所有专家不认可针灸对AMI的治疗效果。
2.2第二轮专家咨询
共发出问卷10份,共收回10份,专家积极系数为100%；所有专家均认可“血瘀证是AMI的基本证候要素”、“气虚证是AMI的基本证候要素”；多数专家认可,对于急性心肌梗死采取新的简化辨证方案“气虚血瘀证为基本证型,痰浊证、阴虚证、阳虚证是主要的证候要素,通过基本证型和单个、多个主要证候要素的结合,覆盖本病的主要证型”,AMI再灌注治疗后,制定病证结合的优化治疗方案,基本治法为益气活血化瘀；兼证治法：通阳化痰(寒痰)或清热化痰(热痰)、养阴、温阳。
3 AMI中西医结合治疗方案的有效性评价
2006年1月-2009年12月纳入符合标准的患者218例(治疗组为152例,对照组66例),治疗组予以益气活血为主中西医结合优化治疗方案,对照组以活血化瘀为主的旧方案,两组的基线资料对比,性别、年龄、梗死类型、梗死部位、泵功能、冠心病危险因素、梗死相关靶血管、病变部位、冠脉病变评分(Gensini评分)、再灌注治疗方式、心功能指标、心肌酶学和血脂指标等方面比较,差异无统计学意义(P>0.05),具有可比性。
3.1住院时间
治疗组的平均住院时间为8.13±4.52天,对照组为10.36±6.77天,两组住院时间比较差异有统计学意义(P<0.05)。按照泵功能的不同进行亚组分析,两组泵功能Ⅰ级、Ⅳ级的AMI患者平均住院时间比较,差异有统计学意义(P<0.05),治疗组的泵功能Ⅰ级、Ⅳ级者平均住院时间相对较对照组短。
3.2住院费用
治疗组的平均住院费用为48570.69±18982.81元,对照组为56706.27±28232.13元,两组住院费用比较,差异有统计学意义(P<0.01)。按照泵功能的不同进行亚组分析,泵功能Ⅰ级两组的平均住院总费用比较,差异有统计学意义(P＜0.05),治疗组的泵功能Ⅰ级者平均住院总费用相对较对照组少。3.3气虚症状记分和血瘀症状积分的比较
气虚症状记分的重复测量方差分析,模型差异有统计学意义(P=287.90,P=0.000),经校正协变量后,两组气虚症状记分比较,差异有统计学意义(P<0.01),治疗组气虚症状记分低于对照组。
血瘀症状记分的重复测量方差分析,模型差异有统计学意义(P=54.18,P=-0.000),经校正协变量后,两组血瘀症状记分比较,差异无统计学意义(P>0.05)。3.4住院期间主要心血管事件发生的比较
主要心血管事件(major adverse cardiac events, MACE)定义为死亡、非致死性再次心肌梗死、靶血管血运重建、中风。住院期间,治疗组死亡9例,靶血管血运重建3例；对照组死亡3例,靶血管血运重建2例,两组MACE发生比较,差异无统计学意义(P>0.05)。3.5预测主要心血管事件发生的因子分析
影响MACE发生因子的Logistics回归分析显示,术前血瘀症记分[OR=1.13,P<0.01,95%CI(1.031,1.237)]、泵功能分级[OR=4.94,P<0.001,95%CI(2.69,9.07)]是预测MACE发生与否的重要因子,血瘀症状记分值>25较血瘀症状记分值≤25的患者院内MACE发生的比值比为2.2。
研究结论：
1围再灌注期的中医证候要素变化规律研究显示,再灌注治疗具有活血、化痰的祛邪作用,再灌注治疗后气虚证成为主要矛盾,气虚血瘀证为再灌注治疗后的主要证候。
2专家共识认为,气虚血瘀证为AMI的基本证型,痰浊证、阴虚证、阳虚证是重要的证候要素,通过基本证型和单个或多个证侯要素的结合,覆盖AMI主要证型。AMI再灌注治疗后,基本治法为益气活血化瘀,补充治法为通阳化痰或清热化痰、养阴、温阳。
3临床对照试验发现,以益气活血为主的AMI中西结合优化治疗方案可降低患者住院时间和住院费用,并有效改善患者的气虚症状。
4血瘀症状记分值>25分和心源性休克可能是AMI患者院内发生心血管事件的主要预测因子。
Background:
Acute myocardial infarction (AMI), a cardiovascular disease, being named "the first killer" in the developed country and the leading cause of mortality cause in global countries, severely damage human health.. Although the incidence of AMI in Chinese is lower than it in Europe or America, the incidence had a rapid growth tendency during the past decades. And the increase of AMI incidence lay serious burden of medical cost on the shoulder of individuals, families and society. To improve the prevention and cure of AMI and to control its medical cost has become a hot research topic in the field of cardiovascular disease and health supervision.
Guangdong Provincial Hospital of Chinese Medicine firstly carried out Percutaneous coronary intervention(PCI) in the national-wide Chinese Medicine(CM) system in 1997 and proposed the theory that PCI was classified into CM clinic system and Qi-deficiency and blood-stasis was the main pathogenesis in patients with coronary heart disease after PCI, establishing benefiting qi and promoting blood circulation as the main treatment after PCI, under the guidance of the theory of blood-activating and stasis-resolving and academic thought of'heart and spleen-related'. This treatment program has been widely used in management of patients after PCI in the field of basic and clinical research and achieved a better clinical effect.
Purpose:
To construct and evaluate the efficacy of optimized management of integrated Chinese and Western Medicine for patients with AMI by the way of syndrome surveys, literature research and expert consultation, combining with the distinguished Chinese academic thought and based on previous research results, which provide a basis for the form to the AMI clinical pathway with integrated Chinese and Western Medicine. Subject and methods:
1 Syndrome Information Collection in Patients with AMI around the Reperfusion Treatment Period Form was formulated to observe the characteristic symptoms and the rules of evolvements for AMI in the perio-reperfusion by the clinical epidemiology and explore the combination rules of AMI syndrome elements by cluster analysis, meanwhile, possible influencing factors were explored by Logistic regression analysis.
2 Based on the integration and optimization of previous research results, optimized management of Integrated Chinese and Western Medicine for patients with AMI was initially established through literature research with evidence-based medicine method and expert consultation with delphi evaluation.
3 The efficacy of the optimized management of Integrated Chinese and Western Medicine for patients with AMI was evaluated by retrospective and prospective controlled study according to clinical epidemiology or DME approach.
Results:
1 Study on the law of distribution and evolvement of syndrome elements during peri-reperfusion period
1.1 Distribution and evolvement of syndrome elements There were significant differences in the frequency of syndrome elements of qi-deficiency, blood-stasis phlegm-heat and phlegm-cold between the third day after reperfusion and before (P<0.05); However, there were no statistic difference in the frequency of yang-deficiency, yin-deficiency, cold-coagulation and qi-stagnation (P>0.05).
1.2 Clustering analysis of syndrome elements If syndrome elements of patients after reperfusion were clustered into three categories, one was qi-deficiency and blood-stasis, the other is phlegm-cold with other syndromes as the remaining.
1.3 Regression analysis of the impact factors of syndrome elements Regression analysis of the impact factors of syndrome elements revealed that: the impact factor of qi-deficiency syndrome was left ventricular ejection fraction (EF) [OR=0.90,95%CI (0.84-0.97)] and impact factors of yin-deficiency syndrome were diabetes [OR=90×109,95%CI(0.00-∞)] and fasting blood glucose[OR=1.39×109,95%CI (1.01-1.90)], with renal dysfunction [OR= 238.45,95%CI (1.13-1304.11)] and EF [OR=0.81,95%CI (0.71-0.91)] for yang-deficiency syndrome, smoking [OR=10.00,95%CI (1.15-86.88)] and hyperlipidemia[OR=4.0×109,95%CI(0.00-∞)] for phlegm-heat syndrome, arrhythmias [OR=2.70,95%CI(0.94-7.75)] and renal dysfunction [OR= 68.02,95%CI (1.31-3524.48)] for cold-coagulation syndrome, age [OR=0.24,95%CI (0.07-0.80)] for qi-stagnation syndrome.
2 Study of expert consultation concerning optimized management of integrated Chinese and Western Medicine for patients with AMI.
2.1 The first round of expert consultation A total of 10 questionnaires were mailed and returned, therefore, the positive coefficient of experts were 100%. With regard to the basic syndrome elements of AMI, the frequency selected by the experts ranked as follows:blood-stasis > qi-deficiency> phlegm-turbidity> yin-deficiency, yang-deficiency> cold-coagulation>qi-stagnation. Regarding to the main Chinese syndromes of AMI based on the differential syndrome treatment, the frequency selected by the experts ranked as follows:qi-deficiency and blood-stasis>qi-deficiency and phlegm-blood-stasis>blockage of phlegm>blood-stasis>cold-coagulation > qi-yin-deficiency> heart-yang-deficiency. The choice of primary CM treatment pattern for patients after reperfusion therapy sorted as follows: activating blood>enforcing Qi>diffusing phlegm>warming yang>enriching Yin>dispersing cold> clearing heat and removing toxin. Lastly, all the experts did not endorse the therapeutic efficacy of acupuncture on patients with AMI.
2.2 The second round of expert consultation Similarly, a sum of 10 questionnaires were mailed and returned, therefore, the positive coefficient of experts were 100%. All the experts approved "Blood-stasis syndrome is a basic syndrome element of AMI," "Qi-deficiency syndrome is also the basic one". Most of the experts adopted a new simplified differential syndrome program for AMI:Qi-deficiency and blood-stasis is the basic syndrome with phlegm-turbidity, yin-deficiency and yang-deficiency as the main syndrome elements, covering the majority of CM syndromes of AMI by differential combination of the basic syndrome with a single or more syndrome elements and recognized optimized management of integrated Chinese and Western Medicine for patients with AMI after reperfusion therapy:the basic treatment method is to benefit qi and promote blood circulation with the supplemental therapy of minor elements such as activating yang and diffusing phlegm or removing heat-phlegm, enriching yin and warming yang.
3 Evaluation of the efficacy of management of integrated Chinese and Western Medicine for patients with AMI 218 cases of AMI patients were included based on the inclusion criteria, among which the treatment group was 152 patients with 66 patients in control group. The treatment group was afforded with the optimized integrative medicine treatment based on benefiting qi and promoting blood circulation and the control group received the treatment of activating blood and resolving stasis. There was no significant difference between two groups concerning gender, age, infarction type, infarction site, pump function, risk factors of CHD, infarct-related target vessel, location of lesion, coronary artery disease score (Gensini score), reperfusion therapy pattern, cardiac function, myocardial enzyme and lipid parameters. In other words, the baseline data of two groups was balanced and comparable.
3.1 Hospital stay
There was statistically significant difference between two groups in the average hospital stay (8.13±4.52 days vs.10.36±6.77days, P<0.05). In subgroup analysis, the difference of the hospital stay was statistically significant between two groups with pump function class I (P＜0.05). Therefore, compared with the control group, the average stay of the treatment group with pump function Class I was relatively short.
3.2 Hospital charges
The comparison between the treatment group and the control group in average hospital charges showed statistically significant difference (48570.69±18982.81 Yuan vs.56706.27±28232.13 Yuan, P<0.01). In subgroup analysis, there was significant statistical difference of.the average hospital costs between two groups with pump function I class (P<0.05) and the cost of treatment group was less than control group.
3.3 The syndrome score of qi-deficiency and the syndrome score of blood-stasis Repeated measures analysis of qi-deficiency syndrome score between two groups showed that model difference was significant (F=287.90, P=0.000). After correcting the covariate, there was statistically significant difference in qi-deficiency syndrome score between two groups (P<0.01) and qi-deficiency syndrome score of treatment group was lower than the control group after treatment.
Repeated measures analysis of blood-stasis syndrome score between two groups disclosed that the model difference was significant (F=54.18, P=0.000) and the difference was no statistically significant in blood-stasis syndrome score between two groups (P> 0.05) after correcting the covariate. 3.4 Major adverse cardiac events
Major adverse cardiac events (MACE) was defied as death, non-lethal re-myocardial infarction, target vessel revascularization and stroke. During hospitalization,9 patients died and 3cases of target vessel revascularization in the treatment group and 3 patients died and 2 cases of target vessel revascularization in control group. The difference of frequency of MACE between two groups was not statistically significant (P> 0.05) 3.5 Predicting factors of major adverse cardiac events
The results of logistics regression analysis of predicting factors of MACE revealed that preoperative blood stasis syndrome scores[OR= 1.13, P<0.0l,95%CI (1.031,1.237)] and the pump function classification [OR= 4.94, P<0.001,95%CI (2.69,9.07)] were important factors impacting MACE events and the ratio of the frequency of MACE in patients whose blood-stasis syndrome scores> 25 to the that of MACE in patients whose blood-stasis syndrome scores≤25 was 2.2.
Conclusions:
1 The Study on the regularity of distribution and evolvements of syndrome elements during peri-reperfusion period shows that reperfusion therapy plays a role of activating blood and diffusing phlegm in terms of CM theory and Qi-deficiency and blood-stasis develop to the major syndrome after reperfusion
therapy.
2 Expert consultation and consensus conclude that qi-deficiency and blood-stasis is the basic syndrome type with phlegm-turbidity, yin-deficiency and yang-deficiency as the main syndrome elements, which covers the majority of CM syndromes of AMI by differential combination of the basic syndrome with a single or more syndrome elements and optimized management of integrated Chinese and Western Medicine for patients with AMI after reperfusion therapy is that the basic treatment method is to benefit qi and promote blood circulation with the supplemental therapy of syndrome element such as activating yang and diffusing phlegm or removing heat-phlegm, nourishing yin and warming yang.
3 The results of clinical controlled trials reveal that the optimized management of integrated Chinese and Western Medicine based on benefiting qi and promoting blood circulation could reduce the stay of hospitalization and hospital costs of AMI patients and improve qi-deficiency symptoms.
4 Blood-stasis syndrome score>25 and cardiac shock may be the significant predictors of major adverse cardiovascular events.
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