Dataset Information

Efficacy and safety of Shexiang Baoxin pill (MUSKARDIA) in patients with stable coronary artery disease: a multicenter, double-blind, placebo-controlled phase IV randomized clinical trial.

ABSTRACT:

Background

The Shexiang Baoxin Pill (MUSKARDIA) has been used for treating coronary artery disease (CAD) and angina for more than 30 years in China. Nevertheless, methodologically sound trials on the use of MUSKARDIA in CAD patients are scarce. The aim of the study is to determine the effects of MUSKARDIA as an add-on to optimal medical therapy (OMT) in patients with stable CAD.

Methods

A total of 2674 participants with stable CAD from 97 hospitals in China were randomized 1:1 to a MUSKARDIA or placebo group for 24 months. Both groups received OMT according to local tertiary hospital protocols. The primary outcome was the occurrence of a major adverse cardiovascular event (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction (MI), or non-fatal stroke. Secondary outcomes included all-cause mortality, non-fatal MI, non-fatal stroke, hospitalization for unstable angina or heart failure, peripheral revascularization, angina stability and angina frequency.

Results

In all, 99.7% of the patients were treated with aspirin and 93.0% with statin. After 2 years of treatment, the occurrence of MACEs was reduced by 26.9% in the MUSKARDIA group (MUSKARDIA: 1.9% vs. placebo: 2.6%; odds ratio?=?0.80; 95% confidence interval: 0.45-1.07; P? =?0.2869). Angina frequency was significantly reduced in the MUSKARDIA group at 18 months (P?=?0.0362). Other secondary endpoints were similar between the two groups. The rates of adverse events were also similar between the two groups (MUSKARDIA: 17.7% vs. placebo: 17.4%, P?=?0.8785).

Conclusions

As an add-on to OMT, MUSKARDIA is safe and significantly reduces angina frequency in patients with stable CAD. Moreover, the use of MUSKARDIA is associated with a trend toward reduced MACEs in patients with stable CAD. The results suggest that MUSKARDIA can be used to manage patients with CAD.

Trial registration

chictr.org.cn, No. ChiCTR-TRC-12003513.

SUBMITTER: Ge JB

PROVIDER: S-EPMC7817287 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Efficacy and safety of Shexiang Baoxin pill (MUSKARDIA) in patients with stable coronary artery disease: a multicenter, double-blind, placebo-controlled phase IV randomized clinical trial.

Ge Jun-Bo JB Fan Wei-Hu WH Zhou Jing-Min JM Shi Hai-Ming HM Ji Fu-Sui FS Wu Yang Y Zhao Yu-Lan YL Qian Jun J Jin Yuan-Zhe YZ Liu Ying-Wu YW Wang Sheng-Huang SH He Sheng-Hu SH Yang Ping P Wu Jie J Lu Feng F Hou Zi-Shan ZS

Chinese medical journal 20210101 2

<h4>Background</h4>The Shexiang Baoxin Pill (MUSKARDIA) has been used for treating coronary artery disease (CAD) and angina for more than 30 years in China. Nevertheless, methodologically sound trials on the use of MUSKARDIA in CAD patients are scarce. The aim of the study is to determine the effects of MUSKARDIA as an add-on to optimal medical therapy (OMT) in patients with stable CAD.<h4>Methods</h4>A total of 2674 participants with stable CAD from 97 hospitals in China were randomized 1:1 to ...[more]

PMID: 33273369

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Project description:BackgroundRecent evidence indicates that Shexiang Baoxin Pill (MUSKARDIA), as an add-on treatment to standard therapy for stable coronary artery disease (CAD), is effective. Nevertheless, the cost-effectiveness of introducing the Shexiang Baoxin Pill (Abbreviation SBP) to the current standard treatment for patients with CAD in China remains unknown.ObjectiveThe objective of this study was to assess the cost-effectiveness of introducing SBP into the current standard treatment in China for patients with CAD.MethodThe effects of two treatment strategies-the SBP group (SBP combined with standard therapy) and the standard therapy group (placebo combined with standard therapy)-were simulated using a long-term Markov model. The simulation subjects might experience non-fatal MI and/or stroke or vascular or non-vascular death events. The study parameters were primarily derived from the MUSKARDIA trial, which was a multicenter, double-blind, placebo-controlled phase IV randomized clinical trial. Furthermore, age-related change, event costs, and event utilities were drawn from publicly available sources. Both costs and health outcomes were discounted at 5.0% per annum. One-way and probabilistic sensitivity analyses were conducted to verify the robustness of the model. Based on the MUSKARDIA trial results, the risk with the events of major adverse cardiovascular events (MACE) was decreased (P < 0.05) in the female subgroup treated with SBP therapy compared with standard therapy. Consequently, a scenario analysis based on subgroups of Chinese females was conducted for this study. Incremental cost-effectiveness ratios (ICERs) were assessed for each strategy for costs per quality-adjusted life-year (QALY) saved.ResultsAfter 30 years of simulation, the SBP group has added 0.32 QALYs, and the cost has been saved 841.00 CNY. Compared with the standard therapy, the ICER for the SBP therapy was -2628.13 CNY per QALY. Scenario analyses of Chinese females showed that, after 30 years of simulation, the SBP therapy has been increased by 0.82 QALYs, and the cost has been reduced by 19474.00 CNY. Compared with the standard therapy, the ICER for the SBP therapy was -26569.51 CNY per QALY. Similar results were obtained in various extensive sensitivity analyses.ConclusionsThis is the first study to evaluate the cost-effectiveness of SBP in the treatment of CAD. In conclusion, SBP as an add-on treatment to standard therapy appears to be a cost-effective strategy for CAD in Chinese patients.

Project description:Background: The coronary microvascular dysfunction has attracted more and more attention in recent years, but there is still a lack of effective treatment. Shexiang Baoxin Pill is one of the commonly used drugs for the treatment of coronary artery disease in China. More recently, some studies found that it has the effect of improving coronary microvascular function. Objective: To evaluate the effects of Shexiang Baoxin Pill for coronary microvascular function. Methods: Databases including MEDLINE, Web of Science, CNKI, Wanfang, The Cochrane Library, EMbase, VIP and CBM were searched from inception to June 2021 to screen out relevant clinical studies. The 2019 version 2 of the Cochrane risk of bias tool (RoB2) were used to assess the methodological quality of the included studies. RevMan 5.3 software was used for meta-analysis. Results: Eleven studies meeting the criteria were included, with a total of 1,075 patients. The results of meta-analysis showed that compared with conventional treatment alone, combination of Shexiang Baoxin Pill and conventional treatment can further increase the coronary flow reserve (CFR) [mean difference (MD) = 0.43, 95%CI (0.28, 0.58), p < 0.000 01], decrease the index of microvascular resistance (IMR) [MD = -4.23, 95%CI (-5.49, -2.97), p < 0.000 01], increase serum nitric oxide (NO) [MD = 11.96, 95%CI (2.74, 21.18), p = 0.001] and decrease serum hypersensitive C-reactive protein (hs-CRP) [MD = -2.49, 95%CI (-3.08, -1.90), p < 0.000 01], but did not increase the time of duration on the exercise testing (TET) [MD = 3.64, 95%CI (-1.17, 8.45), p = 0.14]. In terms of safety, a total of 10 patients developed adverse reactions in the intervention group and 17 patients developed adverse reactions in the control group. Conclusion: Current evidence suggests that Shexiang Baoxin Pill may be effective in the improvement of coronary microvascular function when used in combination with conventional treatment. However, due to the low quality of the included studies, lack of placebo control and high heterogeneity among different studies, we should take a cautious attitude towards this conclusion. Moreover, the safety of Shexiang Baoxin Pill remains uncertain, more high-quality clinical studies are needed to verify the efficacy and safety of this drug in the future. Systematic Review Registration: [website], identifier [registration number: CRD42021265113].

Project description:IntroductionCoronary artery disease (CAD) not amenable to revascularisation indicates that the coronary arteries have severe diffuse lesions or calcifications, or that CAD is complicated with severe multiple-organ disease. Currently, Western medicines available for the treatment of CAD not amenable to revascularisation are limited. Shexiang Baoxin Pill (SBP), a type of Chinese patent medicine, has been widely used to treat CAD in China for many years. Previous studies have shown that long-term administration of SBP (1-2 pills three times daily, for at least 6 months) for treatment of CAD is effective and safe, with a significant, long-term effect. This study aims to evaluate the efficacy and safety of SBP in patients with CAD not amenable to revascularisation.Methods and analysisThis is a multicentre, randomised, double-blinded, placebo-controlled clinical trial. A total of 440 participants will be randomly allocated to two groups: the intervention group and the placebo group. Based on conventional treatment with Western medicine, the intervention group will be treated with SBP and the placebo group will be treated with SBP placebo. The primary outcomes include major adverse cardiovascular events (including angina, acute myocardial infarction, pulmonary embolism and aortic dissection). The secondary outcomes include C reactive protein, B-type natriuretic peptide, ECG, echocardiographic parameters (ejection fraction percentage and the E/A ratio) and hospital readmission rates due to CAD. Assessments will be performed at baseline (before randomisation) and at 24 weeks after randomisation.Ethics and disseminationThe protocol has been approved by the Research Ethics Committee of Guang'anmen Hospital, China Academy of Chinese Medical Sciences in Beijing, China (reference: 2016-129-KY-01). The results of this study will be published in a peer-reviewed journal and will be used as a basis for a multisite trial.Trial registration numberNCT03072121; Pre-results.

Project description:Aim: The Shexiang Baoxin Pill (SBP) has been extensively used to treat cardiovascular diseases in China for four decades, and its clinical efficacy has been widely approved. However, the mechanism by which this is achieved remains largely unexplored. Research attempting to understand the underlying mechanism is ongoing, but the findings are controversial. Here, we aimed to explore the possible mechanism of SBP in myocardial ischemia-reperfusion (I/R) injury using heart single-nucleus and spatial ribonucleic acid (RNA) sequencing. Methods: We established a murine myocardial I/R injury model in C57BL/6 mice by ligating and recanalizing the left coronary artery anterior descending branch. Subsequently, single-nucleus RNA-seq and spatial transcriptomics were performed on mice cardiac tissue. We initially assessed the status of cell types and subsets in the model administered with or without SBP. Results: We used single-nucleus RNA sequencing to comprehensively analyze cell types in the cardiac tissue of sham, I/R, and SBP mice. Nine samples from nine individuals were analyzed, and 75,546 cells were obtained. We classified the cells into 28 clusters based on their expression characteristics and annotated them into seven cell types: cardiomyocytes, endothelial cells, fibroblasts, myeloid cells, smooth muscle cells, B cells, and T cells. The SBP group had distinct cellular compositions and features than the I/R group. Furthermore, SBP-induced cardioprotection against I/R was associated with enhanced cardiac contractility, reduced endocardial cell injury, increased endocardial-mediated angiogenesis, and inhibited fibroblast proliferation. In addition, macrophages had active properties. Conclusion: SBP improves the early LVEF of I/R mice and has a cardioprotective effect. Through sequencing analysis, we observed that SBP can increase the gene expression of Nppb and Npr3 in the infarct area of the heart. Npr3 is related to vascular generation mediated by endocardial cells and requires further research. In addition, SBP increases the number of fibroblasts, inhibits the expression of genes related to fibroblast activation and proliferation, and increases the transformation of endothelial cells into fibroblasts. These findings will help to indicate directions for further research.

Dataset Information

Efficacy and safety of Shexiang Baoxin pill (MUSKARDIA) in patients with stable coronary artery disease: a multicenter, double-blind, placebo-controlled phase IV randomized clinical trial.

Background

Methods

Results

Conclusions

Trial registration

Publications

Efficacy and safety of Shexiang Baoxin pill (MUSKARDIA) in patients with stable coronary artery disease: a multicenter, double-blind, placebo-controlled phase IV randomized clinical trial.

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