| Objectives:Recently several studies demostrated more rapid pulmonary clot resolution and improved hemodynamic disorder than heparin,but significant effect of thrombolytic therapy on important clinical outcomes have maintained unclear.This study mainly systematically assess whether intravenous thrombolysis may reduce the clinical outcomes in patients with acute pulmonary thromboembolism comparing with intravenous heparin,including mortality,recurrent of pulmonary embolism and risk of haemorrhages.Methods:We widely serch English datebase of MDELINE,EMBASE, CENTRAL (the Cochrane Central Register Of Controlled Trails),using Enlish term "pulmonary embolism"or"pulmonary thromboembolism", combined with "thrombolytic drugs","thrombolytic therapy","clot-dissolving medication",as well as all approved thrombolytic drugs:streptokinase,urokinase (Abbokinase),tissue plaminogen activator(TPA) or recombinant tissue-type plasminogen activator(rt-PA),alteplase,prourokinase(Umbralina),tenecteplase. controlled trails or comparative study/or placebo or controlled or clinical or randomised trails are served as limited condition.The published year of database ranges from1953to2012,and language is unrestricted.Search strategy of MeSH headsubject,free text word,and Boolean logical operators are adopted by us.All rearched literatures are imported in the document management of Endnote X4sofeware.To establish inclusion and exclsion criterion so that we may rearch the reference of included documents again.we utilize the revised Jadad scale marking system to evalute the quality of inclued databases,then formulate the assessment sheet of study quality and risk bias form. Revman5.1statistical softwave provided by Cochrane collabration analyzes the extracted related information from included studies through Meta analysis, relative ratio (RR) is set dichotomous variable,and95%confidence interval (CI) is seen as estimated value of each effect size,using x2value as well as in accordence with P value to judge the heterogeneity among studies:If significant heterogeneity (P＜0.1) among studies,is assessed by the chi-square test and and vice versa. Heterogeneity which is I2no more than50%is acceptable in the cochrane database of systematical review,thus applying for fixed effect model to implement the Meta analysis.When I2is more than50%, heterogeneity should be elimited by according methods,such as subgroup analysis,sensitivity analysis,etc.If it still remains significant heterogeneity using professional and statistical knowledges,at present apply radomized effect model to carry out Meta analysis.Finally,meta results are demostrated by drawing the forest map and funnel plot.Results:We preliminarily identified3801documents.Of these,3757studies,such as retrospective studies,reviews,case reports,were exclued through carefully reading articals’headings and abstracts,then removed33uncorrelated ramomized controlled trails(RCT),lastly11RCTs participated in this Meta analysis,which were all English literatures.Only one RCT scored for3in the light of Jadad scale,remained10trails’ scores waved from4to7,which are high quality researchs. We included in all817patients of acute pulmonary thromboembolism(APTE),of these,408patients were assigned to thrombolytic therapy group,the other409patients were allocated to intravenous heparin alone.The results of Meta analysis demostrated that,mortality was reported in all eleven trails, the outcome of heterogeneity test be Chi2=8.41,df=10,P=0.59,I2=0%,so fixed effect model was applied,the benefit of throbolytic therapy reach statistically significant(RR0.57,95%CI [0.32,0.99], Z=1.98, P=0.05),the mean mortality rates in the thrombolytic and heparin group were3.7%and6.7%;There were nine trails reporting recurrent of PE, the outcome of heterogeneity test meaned Chi2=5.43,df=5,P=0.37,I2=8%,fixed effect model was using,this outcome difference was not statistically significant(RR0.61,95%CI[0.31,1.19], Z=1.44, P=0.15),the mean rate of recurrent PE was3.1%、5.3%in the thrombolytic and heparin group respectively; The event of major haemorrage was reported in ten trails,the outcome of heterogeneity test was Chi2=4.22,df=8,P=0.84,I2=0%,fixed effect model was utilized,but thrombolytic therapy increased risk of major bleeding comparing with heparin group(RR1.49,95%CI[1.03,2.15], Z=2.10, P=0.04,13.4%vs8.4%); The incidence of minor haemorrage was reported in four trails, heterogeneity test was Chi2=6.15,df=3,P=0.10,I2=51%, so radomized effect model was used, thrombolytic therapy notably increased risk of minor bleeding (RR3.91,95%CI[1.46,10.48], Z=2.71, P=0.007,40.7%vs9.4%).The clinical endpoints of sensitivity analysis were different from overall effect size,thrombolytic therapy did not redeced patients’ mortality of APE comparing with heparin (Heterogeneity:Chi2=5.73,df=6,P=0.45,I2=0%, fixed effect model,RR0.64,95%CI[0.2951.40], Z=1.11,P=0.27), however,it did not increase risk of major haemorrag(Chi2=3.61,df=5,P=0.61,I2=0%, fixed effect model,RR1.16,95%CI[0.51,2.60], Z=0.35, P=0.73),remained outcomes were in accordence with overall effect size.Conclusions:Compared with intravenous heparin,thrombolytic therapy appear to have clinical benefit of mortality redction,but it does not demonstrate the reduction of recurrent of PE,and it is associated with an increased risk of hemorrhage. Conversely, sensitivity analysis does not reveal a significant difference in mortality between treatments when rt-PA is considered,but is not associated with an increased risk of major hemorrhage. |
PDF Full Text Request