Clinical Evaluation Of Danshen Injection Based On Bayesian Mesh Meta-analysis For Cardiovascular And Cerebrovascular Diseases

BackgroundAccording to the statistic of WHO,the incidence of cardiovascular and cerebrovascular diseases is increasing year by year,which is a major cause of mortality.Recently,Traditional Chinese medicine injection has played an important role in the treatment of cardiovascular and cerebrovascular diseases,especially salvia miltiorrhiza injection classes(SMICs),which is with good economic and social benefits.However,in clinical practice,medical staffs often need to choose better varieties from SMICs.However,the comparative efficacy of SMIC with each other is unknown,mainly because of the restrictions of limited available comparisons and the problem of lumping together different interventions.Therefore,exploring the new method to evaluate the clinical effectiveness and safety of SMICs has great academic significance and clinical value.Based on the speculativesm,this study selected SMIC for treating acute cerebral infarction(ACI)and unstable angina pectoris(UAP)as breakthrough point,and using Meta-analysis and Network Meta analysis(NMA)to comprehensively evaluate the effectiveness and safety of SMIC,and promote safe and reasonable medication.Objective:To assess the clinical effectiveness and safety of SMICs for ACI and UAP.Methods1.Network Meta analysisWe performed data syntheses through Stata and WinBUGS based on the Bayesian statistical model.The results are reported as OR and MD with 95%credible intervals(CrIs).To evaluate the inconsistency between direct and indirect effect estimates for the same comparison,we evaluated each closed loop in the network.In a closed loop,we employed the inconsistency factor(IF)to evaluate heterogeneity among the included studies.To rank the treatments,we used the surface under the cumulative ranking probabilities(SUCRA).2.Meta analysisA systematic literature search was performed in the domestic and foreign database,collect related randomized controlled trials(RCTs).We used Cochrane risk of bias method to evaluate the quality of the included studies.Meta-analysis was used to analyze the included data by RevMan 5.2 software and Stata software.3.Literature reviewBy literature review,we analysed the retrieved literature,including the basic function and safety of SMICs and the published systematic reviews.Results(1)The result of salvia miltiorrhiza injection classes in the treatment of acute cerebral infarctionFor ACI,the 157 RCTs included 15570 patients are two-arm.All patients were diagnosed with acute cerebral infarction.A total of eight SMICs were identified,including injections of Danshen(DS),Fufangdanshen(FFDS),Danhong(DH),Danshenchuanxiongqin,Tanshinone ?A Sulfonate Injection(STS),Salvianolate(SI),Danshenduofensuan(DSDFS),Guanxinning(GXN).All included trials mentioned "random allocation";only 29 trials described random sequence generation method:random number table.11 trials mentioned"blinding".2 trials have incomplete outcome data.All included trials did not gain trial protocol,may lead to selective reporting bias.133 trials reported the total effective rates,112 trials reported the neurological impairment,31 trials reported score of daily activity ability,24 trials reported high blood viscosity,24 trials reported low blood viscosity,25 trials reported plasma viscosity,and 27 trials reported fibrinogen.The Meta-analysis showed that SMICs auxiliary western medicine(WM)has significantly effect in improving the total effective rates,the neurological impairment,and the hemorheology indexes.The Network Meta-analysis indicated that Guanxinning injection had best effect on the total effective rate,however,only one trial included,the results cannot be confirmed.Tanshinone IIA injection had best effect on the neurological impairment,daily activity ability,high blood viscosity,low blood viscosity.Danhong injection had best effect on the plasma viscosity.Danshenduofensuan injection had best effect on fibrinogen.25 trials reported 70 adverse drug reactions/adverse drug events(ADRs/ADEs),major included studies reported headache,rash,sicchasia,emesia and so on.(2)The result of salvia miltiorrhiza injection classes in the treatment of unstable angina pectorisFor UAP,the 172 RCTs included 16306 patients are two-arm.All patients ware diagnosed with unstable angina pectoris.A total of eight SMICs were identified,including injections of Danshen(DS),Fufangdanshen(FFDS),Danhong(DH),Danshenchuanxiongqin,Tanshinone ?A Sulfonate Injection(STS),Salvianolate(SI),Danshenduofensuan(DSDFS),Guanxinning(GXN).All included trials mentioned "random allocation";olny 20 trials described random sequence generation method:random number table.7 trials mentioned"blinding".All included trials did not gain trial protocol,may lead to selective reporting bias.5 trials reported cardiovascular events,8 trials reported nitroglycerin dosage,18 trials reported angina frequency,and 15 trials reported duration of angina attack.172 trials reported the angina curative effect,108 trials reported the electrocardiogram curative effect,32 trials reported total cholesterol(TC),31 trials reported triglycerides(TG),23 trials reported high density lipoprotein cholesterol(HDL-C),and 27 trials reported low density lipoprotein cholesterol(LDL-C).The Meta-analysis showed that SMIC auxiliary western medicine(WM)have significantly effect in improving the total effective rates,reducing cardiovascular events,nitroglycerin dosage,angina frequency,duration of angina attack,and improving blood lipid indicators.Due to the lack of literature quantity,we just performed NMA on the angina curative effect,electrocardiogram curative effect,TC,TQ HDL-C,and LDL-C.The Network Meta-analysis indicated that TST had best effect on the angina curative effect and electrocardiogram curative effect.Salvianolate injection had best effect on TC and LDL-C.Danhong injection had best effect on TG.Danshen injection had best effect on HDL-C.32 trials reported 117 ADRs/ADEs;major included studies reported headache,sicchasia,emesia,stomachache,skin flake bleeder,pruritus and so on.ConclusionThe results showed that SMIC auxiliary WM can improve the efficacy of treating acute cerebral infarction and unstable angina pectoris.NMA indicated that GXN had best effect on clinical curative effect for ACI.STS had best effect on neurologic impairment,activities of daily living,high blood viscosity,low blood viscosity,angina curative effect,and electrocardiogram curative effect.DH had best effect on plasma viscosity and TG;SI had best effect on TC and LDL-C;DSDFS had best effect on fibrinogen.From the literature review of included studies,the safety of SMIC combined with WM was varies,the ADRs still need further study.Based on the limitation of the study,future trials are suggested to pay more attention to the information about patients' life quality and prognosis.And large samples,multi-center,double-blind,randomized,controlled clinical trials are still further needed to confirms the clinical effectiveness and safety of SMIC.