Journal Logo

Research Article: Study Protocol Systematic Review

Efficacy of Shenmai injection for the treatment of chronic heart failure

A protocol of systematic review

Gao, Peng MBa; Wu, Xian MBa; Zhang, Fu-hua MBa; Qiao, Zhi-li MMa; Yang, Li-jie MBb,∗

Author Information
doi: 10.1097/MD.0000000000020663
  • Open

Abstract

1 Introduction

Chronic heart failure (CHF) is a progressive clinical syndrome that results from insufficient blood supply from cardiac output to the metabolic need and accommodating venous return.[1–3] Epidemiological studies showed that the prevalence of CHF is about 1% to 2% among general population,[4,5] which results in high rate of mortality, hospitalization, poor quality of life, and poor prognosis.[4,6,7] Thus, it is very important to prevent and treat patients with CHF.

Shenmai injection (SMI) has been widely utilized for the treatment of patients with CHF.[8–12] Currently, there have been some clinical trials about the efficacy and safety of SMI therapy on CHF. However, most of these studies have low methodological quality [13–25] and no systematic review has conducted on this topic. Hence, this study aims to evaluate the efficacy and safety of SMI in patients with CHF systematically.

2 Methods

2.1 Study registration

This protocol has been registered at INPLASY202050029. This study will follow the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol statement.[26,27]

2.2 Inclusion criteria for study selection

2.2.1 Types of study

This study will include randomized controlled trials (RCTs) in which SMI was used for the treatment of patients with CHF. Nonclinical studies and non-RCTs will be excluded.

2.2.2 Types of participants

This study will include participants who were diagnosed as CHF irrespective sex, age, duration, and severity of CHF.

2.2.3 Types of interventions

In the experimental group, all patients who underwent SMI will be included.

In the control group, there are no limitations to the comparators. However, we will exclude any forms of SMI as control interventions.

2.2.4 Types of outcome measurements

Outcome measurements are all-cause mortality, urine output, serum sodium, and all expected and unexpected adverse events.

2.3 Strategy of literature retrievals

This study will retrieve the electronic bibliographic databases from inception to the March 25, 2020: MEDLINE, PUBMED, Cochrane Library, Web of Science, Scopus, WANGFANG, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. We will search above electronic databases without restrictions of language and publication time. We will consider all potential RCTs for inclusion that explored the efficacy and safety of SMI for patients with CHF. We will create a sample of search strategy for MEDLINE (Table 1). We will adapt similar search strategies for other electronic databases.

Table 1
Table 1:
Search strategy of MEDLINE.

2.4 Data extraction and study quality assessment

2.4.1 Study selection

Two independent reviewers will check titles/abstracts of all potential literatures, and will remove irrelevant studies. We will read full-text of potential trials to determine if they fulfill all inclusion criteria. Excluded studies will be listed with specific reasons in a table. Any divergences will be solved by consulting a third reviewer. The procedure of study selection is demonstrated in a flow chart.

2.4.2 Data extraction and management

Two independent reviewers will extract essential data from all eligible trials using a predefined, pilot-tested extraction sheet. Any dissenting opinions will be resolved by a third reviewer. The essential information includes title, first author, country, time of publication, trial setting, trial design, diagnosed criteria, eligibility criteria, sample size, details of treatments and controls, outcome indicators, and adverse events. We will obtain any insufficient or missing data by email or fax from primary studies.

2.4.3 Methodological study quality assessment

We will assess methodological study quality of each trial by 2 independent reviewers using Cochrane Risk of Bias Tool. If there are conflicts between both of them, we will invite a third reviewer to solve those issues through discussion.

2.4.4 Measurements of treatment effect

In this study, we will estimate continuous data as weighted mean difference or standardized mean difference and 95% confidence intervals (CIs), and we will calculate dichotomous data as risk ratio and 95% CIs.

2.5 Statistical analysis

This study will use RevMan 5.3 software to pool and analyze extracted data. We will use I2 test to identify heterogeneity across trials. We defined it as follows: I2 ≤50% means acceptable heterogeneity, while I2 >50% suggests obvious heterogeneity. If I2 ≤50%, we will pool the data using a fixed-effects model. If minor heterogeneity is identified across trials, we will conduct a meta-analysis based on the sufficient similarity in study and patient characteristics, treatment and controls, and outcome indicators. If I2 >50%, we will pool the data using a random-effects model, and we will perform a subgroup analysis to examine the sources of obvious heterogeneity according to the different study characteristics, types of treatments and controls, and outcome measurements.

In addition, a sensitivity analysis will be performed to verify the stability and robustness of study findings by removing studies with low quality. We will examine the reporting bias by using funnel plot[28] and Egg regression,[29] if this study includes over 10 trials.

3 Discussion

CHF is a rising major cardiovascular disease globally. Although a variety of treatments are available for the treatment of CHF, the efficacy is still limited. SMI is reported to manage cardiovascular disease, especially for CHF. A large number of clinical trials reported that SMI can benefit patients with SMI. However, most of them have poor methodological quality, and their results are inconsistent. Therefore, it is very essential to critically assess the efficacy and safety of SMI for CHF. This study will systematically and comprehensively appraise the efficacy and safety of SMI for the treatment of patients with CHF. The results of this study may provide convinced evidence that can help to determine whether SMI is really effective and safe for the treatment of CHF.

3.1 Ethics and dissemination

This study will not require ethic approval, since no individual patient will be harvested. This study will be published on a peer-reviewed journal.

Author contributions

Conceptualization: Peng Gao, Fu-hua Zhang, Zhi-li Qiao, Li-jie Yang.

Data curation: Xian Wu, Zhi-li Qiao, Li-jie Yang.

Formal analysis: Peng Gao, Zhi-li Qiao.

Investigation: Li-jie Yang.

Methodology: Peng Gao, Xian Wu, Fu-hua Zhang.

Project administration: Li-jie Yang.

Resources: Peng Gao, Xian Wu, Fu-hua Zhang, Zhi-li Qiao.

Software: Peng Gao, Xian Wu, Fu-hua Zhang.

Supervision: Li-jie Yang.

Validation: Peng Gao, Xian Wu, Fu-hua Zhang, Li-jie Yang.

Visualization: Peng Gao, Fu-hua Zhang, Li-jie Yang.

Writing – original draft: Peng Gao, Xian Wu, Zhi-li Qiao, Li-jie Yang.

Writing – review & editing: Peng Gao, Xian Wu, Fu-hua Zhang, Zhi-li Qiao, Li-jie Yang.

References

[1]. Hoffman TM. Chronic heart failure. Pediatr Crit Care Med 2016;17: (8 suppl 1): S119–23.
[2]. Casado Cerrada J, Gómez del Olmo V, Manzano L. Update of treatment in chronic heart failure. Med Clin (Barc) 2015;145:545–50.
[3]. Ewen S, Mahfoud F, Böhm M. Chronic heart failure: current guideline recommendations and innovations. Internist (Berl) 2015;56:791–802.
[4]. Mosterd A, Hoes AW. Clinical epidemiology of heart failure. Heart 2007;93:1137–46.
[5]. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 2016;18:891–975.
[6]. Jones NR, Roalfe AK, Adoki I, et al. Survival of patients with chronic heart failure in the community: a systematic review and meta-analysis protocol. Syst Rev 2018;7:151.
[7]. Cook C, Cole G, Asaria P, et al. The annual global economic burden of heart failure. Int J Cardiol 2014;171:368–76.
[8]. Lu LY, Zheng GQ, Wang Y. An overview of systematic reviews of Shenmai injection for healthcare. Evid Based Complement Alternat Med 2014;2014:840650.
[9]. Chen HD, Xie YM, Wang LX, et al. Systematic review of efficacy and safety of Shenmai injection for chronic heart failure. Zhongguo Zhong Yao Za Zhi 2014;39:3650–61.
[10]. Shi L, Xie Y, Liao X, et al. Shenmai injection as an adjuvant treatment for chronic cor pulmonale heart failure: a systematic review and meta-analysis of randomized controlled trials. BMC Complement Altern Med 2015;15:418.
[11]. Li JS, Wang HF, Li SY, et al. Shenmai injection for chronic pulmonary heart disease: a systematic review and meta-analysis. J Altern Complement Med 2011;17:579–87.
[12]. Zhang L, Hu J, Xiao L, et al. Adverse drug reactions of Shenmai injection: a systematic review. J Evid Based Med 2010;3:177–82.
[13]. Chen J. Clinical efficacy of Shenmai injection in treating elderly patients with chronic heart failure. Contemp Med 2017;23:90–1.
[14]. Yang SZ. Clinical efficacy analysis of Shenmai injection in the treatment of chronic heart failure. Chin Primary Health Care 2016;30:65–6.
[15]. Shi XY. The clinical efficacy of Shenmai injection on elderly patients with chronic congestive heart failure. Inner Mongolian Traditional Chin Med 2016;35:12.
[16]. Dong GR. Systematic review of the efficacy and safety of Shenmai injection in the treatment of chronic heart failure. J Cardiology Integr Chin Western Med 2016;4:161.
[17]. Wu QB. Observation of the therapeutic effect of Shenmai injection on chronic heart failure. Hubei J Traditional Chin Med 2016;38:39–40.
[18]. Duan SP. Observation of the clinical efficacy of Shenmai injection in the treatment of chronic heart failure. Primary Med Forum 2016;20:2388–9.
[19]. Guo HY, Zhang H. 34 cases of chronic heart failure treated with Shenmai injection. Mod Distance Educ Chin Med 2015;13:36–7.
[20]. Wang LM. Observation on the therapeutic effect of Shenmai injection on chronic heart failure. Chin Med Guide 2015;13:218.
[21]. Xian S, Yang Z, Lee J, et al. A randomized, double-blind, multicenter, placebo-controlled clinical study on the efficacy and safety of Shenmai injection in patients with chronic heart failure. J Ethnopharmacol 2016;186:136–42.
[22]. Ma RG, Wang CX, Shen YH, et al. Effect of Shenmai Injection on ventricular diastolic function in patients with chronic heart failure: an assessment by tissue Doppler imaging. Chin J Integr Med 2010;16:173–5.
[23]. Luo L. The effect of Shenmai injection on BNP level and cardiac function in patients with chronic heart failure. J Cardiovasc Cerebrovasc Dis Integr Chin Western Med 2018;16:3643–5.
[24]. Luo H, Mu W, Zhang JH, et al. Observation of clinical efficacy of Shenmai injection in the treatment of chronic heart failure with deficiency of both qi and yin. World Latest Med Inform Dig 2018;18:27–8.
[25]. Chen YB. Observation of the therapeutic effect of Shenmai injection on patients with chronic heart failure. Electron J Clin Med Literature 2017;4:6689–92.
[26]. Shamseer L, Moher D, Clarke M, et al. PRISMA-P Group. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ 2015;349:g7647.
[27]. Moher D, Shamseer L, Clarke M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 2015;4:1.
[28]. Sutton AJ, Duval SJ, Tweedie RL, et al. Empirical assessment of effect of publication bias on meta-analyses. BMJ 2000;320:1574–7.
[29]. Egger M, Davey Smith G, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629–34.
Keywords:

chronic heart failure; efficacy; safety; Shenmai injection

Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.