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

Current Status and Evaluation of Randomized Clinical Trials of Traditional Chinese Medicine in the Treatment of Cardiovascular Diseases

“…Shexiang Baoxin pill (MUSKARDIA), as an additional medicine on the basis of standard treatment for patients with stable CAD, can safely reduce the frequency of angina in patients with stable CAD. In addition, MUSKARDIA has a potential effect of decreasing incidence of MACE (major adverse cardiovascular event) in patients with stable CAD [ 20 ]. A total of 2674 participants with stable CAD from 97 hospitals in China were divided into a MUSKARDIA or placebo group and observed for 24 months.…”

Protective Effect of Shexiang Baoxin Pill on Myocardial Ischemia/Reperfusion Injury in Patients With STEMI

“…Myocardial I/R injury has a multimodal pathogenesis and thus treatment of I/R injury may require targeting a variety of factors to achieve better results (Davidson et al, 2019;Li et al, 2019). SBP is a traditional compound preparation composed of a variety of Chinese herbs Tian et al (2018), diminishes the level of cardiac troponin T (cTNT) and cardiac troponin I (cTNI) in STEMI patients (Lu et al (2018), significantly decreases the frequency of angina in patients with stable CAD Ge et al (2021), and lower the MACCE in patients with NSTE-ACS (Zhou et al, 2016). However, we confirmed that SBP was able to reduce the myocardial infarction area and relieve I/R injury assessed by SPECT that accurately assessed I/R injury and myocardial infarction area (Bøtker et al, 2010).…”

“…The pathogenesis of I/R injury is diverse Hausenloy et al (2017) , and cooperative treatment through different mechanisms may be a new approach for I/R injury treatment ( Davidson et al, 2019 ). Shexiang Baoxin Pill (SBP) is a traditional Chinese medicine compound preparation, it is mainly composed of artificial moschus, radix ginseng, calculus bovis artifactus, cortex cinnamomi, styrax, venenum bufonis, and borneolum syntheticum, and is mainly used to treat CHD ( Lu et al, 2018 ; Ge et al, 2021 ). The extract of the components of SBP reduces I/R injury, myocardial remodeling, and myocardial infarction area in animals through multiple mechanisms.…”

Efficacy and Safety of Shexiang Baoxin Pill for Coronary Heart Disease after Percutaneous Coronary Intervention: A Systematic Review and Meta-analysis

“…Modern pharmacological studies have shown that SBP and its active ingredients have pleiotropic effects in protecting the circulatory system, such as promoting therapeutic angiogenesis, restoring myocardial function, reducing inflammation, and improving endothelial dysfunction, which may be necessary for the curative effect of CHD after PCI. At the same time, evidencebased clinical studies have shown that SBP is advantageous as an adjuvant treatment in numerous cardiovascular diseases, such as stable angina, myocardial infarction, and heart failure [7][8][9]. However, the clinical evidence regarding the efficacy of SBP in the treatment of CHD after PCI has not been well summarized yet.…”