Efficacy and Safety of Traditional Chinese Medicine Injections for Heart Failure With Reduced Ejection Fraction: A Bayesian Network Meta-Analysis of Randomized Controlled Trials

Abstract

Background: Heart failure as an important issue in global public health, has brought a heavy economic burden. Traditional Chinese medicine injections (TCMIs) have significant effects on heart failure with reduced ejection fraction (HFrEF). However, it is difficult for clinicians to identify the differences in clinical efficacy and safety of various TCMIs. The purpose of this study is to compare the efficacy and safety of various TCMIs for treating HFrEF by conducting a Bayesian network meta-analysis (NMA) and to further provide references for clinical decision-making. Methods: The clinical randomized controlled trials of TCMIs for treating HFrEF were searched in seven database from inception to August 3rd, 2021. The Cochrane collaboration's tool was used to assess the risk of bias. NMA was performed in a Bayesian hierarchical framework. The surface under the cumulative ranking curve (SUCRA), the multi-dimensional efficacy analysis, the comparison-adjusted funnel plot, and the node-splitting analysis were conducted using R software. Results: A total of 107 eligible RCTs involving 9,073 HFrEF patients and 6 TCMIs were included. TCMIs include Huangqi injection (HQ) also called Astragalus injection, Shenfu injection (SF), Shengmai injection (SGM), Shenmai injection (SM), Xinmailong injection (XML), and Yiqifumai lyophilized injection (YQFM). The results of NMA and SUCRA showed that with conventional treatment (CT) as a common control, in terms of clinical efficacy, CT + XML was most effective in New York Heart Association cardiac functional classification efficiency, brain natriuretic peptide, and N-terminal pro-brain natriuretic peptide; the CT + SM was most effective in 6-min walking test, left ventricular end-diastolic diameter, left ventricular end-systolic diameter and cardiac output; the CT + YQFM was most effective in left ventricular ejection fraction; the CT + HQ was most effective in stroke volume; the CT + SF was most effective in Minnesota Living with Heart Failure Questionnaire. In terms of safety, there was no significant difference between CT + TCMIs and CT. Conclusion: This Bayesian network meta-analysis results show that the combination of qualified TCMIs and CT is more effective for HFrEF patients than CT alone, and CT + XML and CT + SM may be one of the potential optimal treatments. Also, the safety of these TCMIs needs to be further observed. However, due to some limitations, the conclusions need to be verified by more large-sample, double-blind, multi-center RCTs.

Keywords: bayesian model; heart failure; network meta-analysis; randomized controlled trial; traditional chinese medicine; traditional chinese medicine injection.

FIGURE 1

Flowchart of the literature screening process. CBM, Chinese BioMedical Literature Database; CNKI, China National Knowledge Infrastructure; VIP, VIP Chinese Science and Technology Journal Database; LVEF, left ventricular ejection fraction; RCT, randomized controlled trial; n, the number of articles.

FIGURE 2

Network diagrams for different outcomes. (A) New York Heart Association cardiac functional classification efficiency; (B) 6-min walking test; (C) left ventricular ejection fraction; (D) left ventricular end-diastolic diameter; (E) left ventricular end-systolic diameter; (F) cardiac output; (G) stroke volume; (H) brain natriuretic peptide; (I) N-terminal pro-brain natriuretic peptide; (J) Minnesota Living with Heart Failure Questionnaire. CT, conventional treatment; HQ, Huangqi injection; SF, Shenfu injection; SGM, Shengmai injection; SM, Shenmai injection; XML, Xinmailong injection; YQFM, Yiqifumai lyophilized injection.

FIGURE 3

Risk of bias graph of the included RCTs. The vertical axis represents the risk of bias items, and the horizontal axis represents the percentage of the number of RCTs. For the outcome whose evaluation process is objective, the “unclear risk of bias” should be regarded as “low risk of bias”.

FIGURE 4

Surface under the cumulative ranking curve (SUCRA) plots for different outcomes. The vertical axis represents cumulative probabilities and the horizontal axis represents rank. NYHA, New York Heart Association cardiac functional classification efficiency; 6WMT, 6-min walking test; LVEF, left ventricular ejection fraction; LVEDD, left ventricular end-diastolic diameter; LVESD, left ventricular end-systolic diameter; CO, cardiac output; SV, stroke volume; BNP, brain natriuretic peptide; NT-proBNP, N-terminal pro-brain natriuretic peptide; MLHFQ, Minnesota Living with Heart Failure Questionnaire; CT, conventional treatment; HQ, Huangqi injection; SF, Shenfu injection; SGM, Shengmai injection; SM, Shenmai injection; XML, Xinmailong injection; YQFM, Yiqifumai lyophilized injection.

FIGURE 5

Multi-dimensional efficacy analysis results. (A) NYHA and 6WMT; (B) NYHA and LVEF; (C) NYHA and BNP. Interventions located in the upper right corner indicate optimal therapy for two different outcomes. NYHA, New York Heart Association cardiac functional classification efficiency; 6WMT, 6-min walking test; LVEF, left ventricular ejection fraction; BNP, brain natriuretic peptide; CT, conventional treatment; HQ, Huangqi injection; SF, Shenfu injection; SGM, Shengmai injection; SM, Shenmai injection; XML, Xinmailong injection; YQFM, Yiqifumai lyophilized injection.

FIGURE 6

Funnel plot of left ventricular ejection fraction. CT, conventional treatment; HQ, Huangqi injection; SF, Shenfu injection; SGM, Shengmai injection; SM, Shenmai injection; XML, Xinmailong injection; YQFM, Yiqifumai lyophilized injection.

FIGURE 7

Consistency test for the New York Heart Association cardiac functional classification efficiency. CT, conventional treatment; SM, Shenmai injection; XML, Xinmailong injection.