Efficacy and Safety of Fuzi Formulae on the Treatment of Heart Failure as Complementary Therapy: A Systematic Review and Meta-Analysis of High-Quality Randomized Controlled Trials

Abstract

Objective. Heart failure is a major public health problem worldwide nowadays. However, the morbidity, mortality, and awareness of heart failure are not satisfied as well as the status of current treatments. According to the standard treatment for chronic heart failure (CHFST), Fuzi (the seminal root of Aconitum carmichaelii Debx.) formulae are widely used as a complementary treatment for heart failure in clinical practice for a long time. We are aiming to assess the efficacy and safety of Fuzi formulae (FZF) on the treatment of heart failure according to high-quality randomized controlled trials (RCTs). Methods. RCTs in PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), and Wanfang Database were searched from their inception until June 2019. In addition, the U.S. National Library of Medicine (clinicaltrials.gov) and the Chinese Clinical Trial Registry (http://www.chictr.org.cn) were also searched. We included RCTs that test the efficacy and safety of FZF for the treatment of heart failure, compared with placebo, CHFST, or placebo plus CHFST. The methodological quality of included studies were evaluated by the Cochrane Collaboration’s tool for assessing risk of bias. RCTs with Cochrane risk of bias (RoB) score ≥4 were included in the analysis. The meta-analysis was conducted through RevMan 5.2 software. The GRADE approach was used to assess the quality of the evidence. Results. Twelve RCTs with 1490 participants were identified. The studies investigated the efficacy and safety of FZF, such as FZF plus the CHFST vs placebo plus CHFST (n = 4), FZF plus CHFST vs CHFST (n = 6), FZF plus digoxin tablets (DT) plus CHFST vs placebo plus DT plus CHFST (n = 1), and FZF plus placebo plus CHFST vs placebo plus DT plus CHFST (n = 1). Meta-analysis indicated that FZF have additional benefits based on the CHFST in reducing plasma NT-proBNP level, MLHFQ scores, Lee’s heart failure scores (LHFs), and composite cardiac events (CCEs). Meanwhile, it also improved the efficacy on TCM symptoms (TCMs), NYHA functional classification (NYHAfc), 6MWD, and LVEF. Adverse events were reported in 6 out of 12 studies without significant statistical difference. However, after assessing the strength of evidence, it was found that only the quality of evidence for CCEs was high, and the others were either moderate or low or very low. So we could not draw confirmative conclusions on its additional benefits except CCEs. Further clinical trials should be well designed to avoid the issues that were identified in this study. Conclusion. The efficacy and additional benefits of FZF for CCEs were certain according to the high-quality evidence assessed through GRADE. However, the efficacy and additional benefits for the other outcomes were uncertain judging from current studies. In addition, the safety assessment has a great room for improvement. Thus, further research studies are needed to find more convincing proofs.

Clinical Efficacy of Qili Qiangxin Capsule Combined with Western Medicine in the Treatment of Chronic Heart Failure: A Systematic Review and Meta-Analysis

“…Complementary and alternative medicine therapies have become increasingly popular and are used regularly by patients with chronic disorders [9]. Currently, the combination of traditional Chinese medicine (TCM) and western medicine has been widely used for the CHF treatment [10][11][12]. According to the perspective of TCM, the etiology of CHF is the yang deficiency of heart which is the result of the inadequacy of Qi and blood, blood stasis, and phlegm-dampness.…”

Preliminary investigation on the analysis of the whole components of Pogejiuxin decoction and its formulation pattern based on ultrahigh‐performance liquid chromatography with quadrupole time‐of‐flight mass spectrometry

“…Research on PGJXD has generally focused more on assessing its cardiac function and studying classic drug pairs in the formula, but the investigation of the material basis of the entire PGJXD formula and the development of dosage rules have not been reported in the literature 16,17 . With the goal of establishing an efficient quality control and compositional analysis system for PGJXD, and to explore comprehensively the scientific connotations of the rules of compounding, this article comprehensively reveals the impact of each ingredient compatibility on its overall chemical composition from the “point” of single drugs, drug pairs and split formula group research to the “surface” of compound formula research, in order to reveal the theoretical underpinnings and potential mechanism of action of PGJXD compatibility.…”

“…PGJXD is made up of processed A. carmichaelii (PAC, 150 g), Zingiber officinale (Zor, 60 g), Glycyrrhiza uralensis (Gly, 60 g), Cornus officinalis (Cor, 120 g), keel (30 g), oyster powder (30 g), live magnet (30 g), ginseng (30 g, separately decocted in thick juice) and musk (0.5 g, divided into two doses) 16 . The current research on this formula is primarily focused on the assessment of cardiac function and the composition of the monarch A. carmichaelii 17 . However, greatly lacking is the analysis of the chemical compositions and rules of this formula.…”

“…16 The current research on this formula is primarily focused on the assessment of cardiac function and the composition of the monarch A. carmichaelii. 17 However, greatly lacking is the analysis of the chemical compositions and rules of this formula. It is important to clarify the chemical constituents of the compound formula in order to elucidate the material basis of the medicinal effect, set quality standards and guide clinical use.…”

Yang-xin-xue keli exerts therapeutic effects via regulating mitochondrial homeostasis and function in doxorubicin-induced rat heart failure

“…It has been reported that Shensong Yangxin capsules, a combined herbal formulation widely used in China for the treatment of arrhythmias, have the benefits of suppressing ventricular premature complexes (VPCs) and improving cardiac function ( Wang X. et al, 2017 ). Yang et al (2019 ) assessed the efficacy and safety of Fuzi formulae (FZF) in treating CHF, and they demonstrated that FZF exerts efficacy and additional benefits on CHF. It has also been reported that gallic acid improves cardiac dysfunction and fibrosis in pressure overload-induced heart failure ( Jin et al, 2018 ), and it can produce benefits for vascular calcification ( Kee et al, 2014 ), cardiac hypertrophy, and fibrosis ( Ryu et al, 2016 ), hypertension ( Jin et al, 2017a ), and oxidative stress ( Jin et al, 2017b ).…”