Effect Of Shenmai Injection On The Mortality Rate And Complications Of Patients With Acute Myocardial Infarction: A Meta-analysis

BackgroundAcute myocardial infarction(AMI) is an acute condition of sharp reduction or cut off of coronary blood supply causing part of the myocardium suffer from severe persistent,ischaemia,and consequently partial myocardial necrosis.Often it is complicated with arrhythmia,shock,heart failure and post-infarction angina pectoris etc.This disease,in Traditional Chinese Medicine(TCM),pertains to the category of "True cardiodynia"."LingShu-Que Disease" described "True Cardiodynia, extremities turn pallor up to joints level,severe heart pain,onset in morning die in evening,onset in evening die in the next morning." The presentation of AMI is rapid onset,severely ill,and threatening prognosis,it is a commonly seen emergency critical condition in the cardiac unit.Its occurrence and mortality rate is high.In developed countries,the occurrence rate is even higher.According to the statistics of USA in 2004,almost 0.9 million new cases of AMI are diagnosed every year,42%of the cases die within 1 year and half of the death occurs when the patients were on their way to the emergency of the hospital after the onset.In recent years,with the continuous improvement of the standard of living in China,the number of people with high blood pressure,high blood sugar,high blood cholesterol is increasing,thus, the incidence of Coronary Artery Disease(CAD) also inclines every year.Among different types of CAD,AMI is the most acute,with highest mortality rate and the most hazardous condition.Investigation by CAPCS indicates that the risk factors for cardiovascular diseases in China shows significant increase.There is 0.5 million new cases being diagnosed every year,and the accumulated frequency is 2 million by now. AMI has become a major disease that threatens the health of the population.To reduce the mortality rate of AMI and to prevent and cure the complication of AMI effectively becomes an important issue for the public health services.The mid-70s and 80's,many areas of China used Chinese and Western Medicine to treat AMI,and a wealth of experience had been accumulated.Many huoxuehuayu prescriptions represented by GuanXin No.Ⅱused in treating myocardial infarction with coronary heart disease,and there are lots of research and documents about it. Good results had been gained in controlling the symptoms,preventing the complications and deccreasing the mortality rate.However,the advantages of Chinese medicine in preventing and treating AMI weakens at present,and large sample, rigorous designed clinical trials rare.With the rapid development of modern medicine, the treatment of myocardial infarction with coronary heart disease,make great progress.The importance of coronary recanalization in modern medicine is more and more higher,and the AMI mortality rate decreases sharply.However,myocardial ischemia-reperfusion injury and myocardial stunning after coronary artery recanalization,and half a year after PCI,the restenosis rate is 30～40%,so we must pay attention to the high incidence.The indication,contraindication,and economy of thrombolysis limited its widespread clinical application.But compared with thrombolysis and PCI,the advantages of activating blood circulation to dissipate blood stasis in the treatment of AMI may no longer apparent.How to use the advantages of traditional Chinese medicine syndrome differentiation and treatment disease and adjustment the body in all,in coronary heart disease,myocardial infarction,making further contributions which are the important problem we face.In recent years,in the therapy of AMI such as yiqi,yangyin,fuzheng Chinese medicine vein preparation can play important role,and in the treatment of combining traditional Chinese and western medicine,complementary advantages of better effect. Wang Shuoren et.al.using Logistic Regression Analysis to study the factors that able to reduce the mortality rate of AMI,(in order of low risk to high risk):Reperfusion, Tiaozhi drugs,intravenous drip of chinese medicine,β-blockers,low-molecular heparin,ACEI drugs,digitalis,indicates that the effect of intravenous form of chinese medicine in reducing the mortality rate of AMI is at the third place just listed behind Reperfusion and Tiaozhi drugs,its efficacy is not negligible.At present,it is common to combine the practice of TCM Syndrome-Differentiation and corresponding Treatment with Multiple Approach of Western Medicine in treating AMI.Since 1992, Shenmai Injection(SMI) was classified as the first batch of emergency medication by Ministry of Public Health of China;it was widely used in hospitals at all levels.Up till now there are a large number of published observational studies about the curative effect of SMI in treating AMI.However,using these data which are based on the clinical experience of individual practitioner,sporadic cases or some observational studies,to formulate the therapeutic regimen or justify the efficacy of certain medication,can easily lead to biases.At present,there is still a lack of Prospective, Multicenter-RCT studies on the therapeutic effect of SMI in treating AMI and also lacking of Systematic Review on the effect of SMI on mortality rate and major complication of AMI.ObjectiveTo systematically evaluate the therapeutic efficacy of SMI on the mortality rate and major complication incidence rate of acute myocardial infarction(AMI),so as to provide a more comprehensive and reliable theoretical and clinical basis to justify the curative rate of SMI in treating AMI and also to provide guidance for clinical doctors in decision making on the utilization of SMI as an adjuvant therapy for AMI.Methods1.According to the requisition of systematic evaluation,we formulate detailed standardization of the inclusion and exclusion criteria including the type of research subjects,interventions and outcome of events. 2.We developed a systematic,comprehensive search strategy according to laying standardization.Literature were retrieved by computerized searching from Cochrane Central Register of Controlled Trials(Issue 6,2008),PubMed(1980-2008), OVID(1979-2008.12),CBM(1979-2008.12),CNKI(1994-2008),CMCC (1994-2008),and those in Chinese Conference Treatises and Periodal in cardiovascular disease were handed searched(update to Dec 2008).3.We evaluate the methodological quality of the included studies in accordance with the quality of the evaluation criteria of randomized controlled trials,evaluation item including the method of random allocation,concealed sub-blind law and attrition bias in the assessment.Quality of them was evaluated with the method recommended in Cochrane Reviewer's Handbook 4.2.6,the quality of classification including A,B, C three grades.4.We collect the relevant research information data after rigorous evaluation of the quality,and mainly collect the incidence of the outcome of data.Statistical analysis was performed using the Cochrane Collaboration's Rev Man 4.2.2 software. Enumeration data use relative risk(Relative Risk,RR) manifestates,and measurement data use Weighted Mean Difference(WMD) manifestates,both all preaent 95%Confidence Interval(CI).We examine the clinical heterogeneity before merge the research,and we would use sub-group analysis if the interventions are different.Use chi-square to test the statistical heterogeneity of every study,and madeα= 0.1 for the size of test.We analyse data using fixed-model if there is no statistical heterogeneity,otherwise random-model was used.Results1.The descriptive analysis of all research character:The number of the patients who suffered from AMI is 901 among the 7 RCT. There are 444 patients in the SMI treated group which takes 49.28 percent of all the patients.However,the number of the patients in the controlled group is 457 which takes 50.72 percent.All the included RCT were graded as C.All the included RCT reported the dead circumstances,there are 22 patients in the SMI treated group and 40 patients in the controlled group;4 included RCT reported the heart failure circumstances,there are 43 patients in the SMI treated group and 71 patients in the controlled group;3 RCT reported the postinfarction angina pectoris circumstances, there are 14 patients in the SMI treated group and 24 patients in the controlled group; 4 RCT reported the recanalization circumstances,there are 252 patients in the SMI treated group and 263 patients in the controlled group;3 RCT reported the reperfusion arrhythmias circumstances,there are 42 patients in the SMI treated group and 75 patients in the controlled group;5 RCT reported the arrhythmia circumstances, there are 50 patients in the SMI treated group and 99 patients in the controlled group; All the observation indicatrixes were occurrence circumstances during duration of hospital stay.2.The results of meta-nanlyses The results of meta-nanlyses indicated that the RR and 95%CI calculated by the fixed effect model of the mortality rate was 0.55, [0.33,0.90],total effect:Z=2.39,P=0.02;myocardial failure occurrence rate was: RR=0.60,95%CI[0.45,0.80],tatal effect:Z=3.44,P=0.0006;postinfarction angina pectorisrate was 0.59,[0.34,1.03],total effect:Z=1.86,P=0.06;recanalization rate: RR=1.01,95%CI[0.93,1.10],total effect:Z=0.32,P=0.75;reperfusion arrhythmias occurrence rate:RR=0.58,95%CI[0.45,0.73],total effect:Z=4.48,P＜0.00001; The results of meta-nanlyses indicated that the RR and 95%CI calculated by the random effect model of arrhythmia rate:RR=0.53,95%CI[0.30,0.94],tatal effect:Z=2.19,P=0.03.3.Re-infarction incidence rate Owing to lacking of enough clinical research about the effect on re-infarction rate and lacking of evidence about the influence on it, so we can't utilize meta-analysis to evaluate the influence on re-infarction rate.4.Analysis of publication bias We can't analysis the publication bias because of too little study literature included.5.Security Wei Danxia 2001 reported no bleeding tendency and other side adverse reactions;the remaining studies reported no adverse reactions. Conclusions1.According to the present evidence,there are different effections of SMI on mortality rate,myocardial failure occurrence rate,postinfarction angina pectoris rate, recanalization rate,reperfusion arrhythmias occurrence rate and arrhythmia rate.The combined use of SMI with the conventional therapy of modern medicine can decrease the fatality rate,myocardial failure occurrence rate,postinfarction angina pectoris rate,reperfusion arrhythmias occurrence rate and arrhythmia rate.But the postinfarction angina pectoris rate was slightly cut down.Besides,there is nearly no difference on recanalization rate between the SMI treated group and the controlled group.2.Owing to lacking of enough clinical research about the effect on relnfarction rate,so we can't utilize meta-analysis to evaluate the influence on plain-infarction rate.3.There is no report about serious adverse effect.4.As the evidence obtained is not strong enough owing to only seven literature with a total of 901 cases of AMI and the rather poor quality of current studies enclosed,further studies with high-quality,large-scale trials are required,for identification.Subject to publication bias,study time,documentation quality and other factors,the advantage of Shenmai injection in treating AMI needs further study and explore.