From June 27 to 30, 2024, the 18th Eastern Cardiology Conference was held in Shanghai. On the afternoon of June 29, at the forum on the integration of traditional Chinese and Western medicine, Professor Shi Haiming from Huashan Hospital affiliated to Fudan University introduced the MUST research series of Musk Baoxin Pills, including MUST-A (main study), MUST-D (diabetes subgroup analysis), MUST-E (pharmacoeconomic research) and MUST-F (female subgroup analysis) and other research results, and more than 100 experts and scholars in the cardiovascular field from all over the country listened to the conference report.
At the beginning of the report, Professor Shi introduced the research background of the Musk Baoxin Pill MUST study, and pointed out that for a long time, patients with coronary heart disease still have a greater cardiovascular risk after receiving standard treatments such as aspirin and statins. For this reason, traditional Chinese medicine, which is widely used in the treatment of coronary heart disease in clinical practice, is a very good supplement, but there is still a lack of large-scale randomized controlled trials in traditional Chinese medicine research, and there is a lack of hard endpoint indicators.
MUST-A Study: Master Study
In order to verify its long-term efficacy and safety, in 2011, Academician Ge Junbo from Zhongshan Hospital Affiliated to Fudan University and Professor Fan Weihu from Huashan Hospital Affiliated to Fudan University led a large-scale evidence-based study of Musk Baoxin Pill in line with international norms - MUST Study, which is a multicenter, randomized, double-blind, placebo-controlled phase IV trial. Finally, 2673 patients with stable coronary heart disease (CAD) in 97 hospitals were enrolled, and the clinical efficacy of Musk Baoxin Pill combined with standard therapy in the treatment of CAD patients was evaluated. All endpoint events of the MUST study will be adjudicated by the endpoint event review committee led by Academician Chen Keji.
In 2021, the results of the 10-year MUST research were finally published in Chinese Medical Journal (English version of Chinese Medical Journal, impact factor 6.133). The results showed that in terms of the incidence of cardiovascular adverse events (MACE) at the primary efficacy endpoint (hard endpoint), the K-M survival curves of the two groups gradually separated after 18 months, and the incidence of MACE in the Musk Baoxin Pill group was 26.9% lower than that in the placebo group at 24 months, suggesting the characteristics of long-term effect of Musk Baoxin Pill and good safety.
Professor Shi pointed out that the MUST study confirmed with high-quality evidence-based research evidence that the combination of Musk Baoxin Pill in the treatment of chronic stable coronary heart disease has long-term effectiveness and safety, and significantly improves the stability and attack frequency score of angina, which can effectively alleviate patients' symptoms and significantly improve their quality of life, providing theoretical support for the long-term treatment of coronary heart disease with Musk Baoxin Pill.
MUST-D研究：糖尿病亚组分析
The MUST-D study (full name is "Efficacy and Safety of Musk Baoxin Pill in Patients with Stable Coronary Heart Disease and Diabetes Mellitus: A Subgroup Analysis of a Randomized Clinical Trial") conducted a subgroup analysis of 716 patients with coronary heart disease and diabetes mellitus based on data from 97 research centers in the MUST study.
The findings were published in Chinese Medical Journal in January 2023. The results showed that for patients with coronary heart disease and diabetes mellitus, the incidence of MACE in the Musk Baoxin pill group was 45.8% lower than that in the placebo group, and the incidence of secondary endpoint events was 32.3% lower than that in the placebo group (P=0.017). For patients with poor glycemic control, the incidence of MACE in the Musk Baoxin pill group was 45.5% lower than that in the placebo group, and the incidence of secondary endpoint events was 63.6% lower than that in the placebo group (P=0.04). Long-term use of Musk Baoxin Pill has a similar incidence of various adverse events as placebo.
The results of the MUST-D study showed that Musk Baoxin Pill showed good efficacy in patients with coronary heart disease with diabetes, reducing the incidence of major adverse cardiovascular events, as well as reducing the incidence of all-cause death, cardiovascular events, hospitalizations and coronary angioplasty in this population, in which patients with poor glycemic control were able to benefit more and have a good drug safety profile.
The MUST-E study: a pharmacoeconomic study
The MUST-E study (full name is "Pharmacoeconomic Analysis of Musk Baoxin Pill in Patients with Chronic Stable Coronary Heart Disease") is a cost-effectiveness study on the use of proprietary Chinese medicines in patients with coronary heart disease in China, by extracting the data of the MUST study, establishing a Markov model, and conducting the pharmacoeconomic evaluation of Musk Baoxin Pill in the treatment of coronary heart disease, and using sensitivity analysis to verify the robustness of the model. The findings were published in the journal PLOS ONE (Impact Factor: 3.752).
The results of the study showed that compared with placebo combined with standard drugs, the incremental cost-effect ratio (ICER) for the whole population with coronary heart disease was -2,628.13 yuan/QALY (quality-adjusted life years), that is, the treatment cost of Musk Baoxin Pill was lower and the health output was higher. The results of the analysis of the subgroup of women with coronary heart disease showed that the combination of musk baoxin pills and standard drugs had more benefits for women, and the ICER of the female subgroup was -26,569.51 yuan/QALY.
Overall, compared with placebo combined with standard drugs, Musk Baoxin Pill combined with standard drugs has lower long-term costs and higher health outcomes in the treatment of coronary heart disease, and is a treatment option with pharmacoeconomic advantages.
MUST-F study: subgroup of female patients
The MUST-F study (full name is "Efficacy and Safety of Musk Baoxin Pill in Women with Chronic Stable Coronary Heart Disease: A Subgroup Analysis of RCTs") conducted a subgroup analysis of data from 776 women in the MUST study. The results showed that at 24 months, among the female subgroup of CAD patients, the Musk Baoxin pill group significantly reduced the incidence of MACE with a good safety profile.
In response to the results of the MUST study series, Professor Shi pointed out that in clinical practice, the concept of "patient-centered" has been paid more and more attention, and the length and quality of life of patients should be fully considered in the design of future clinical research endpoints, taking into account the hard endpoints and soft endpoints that reflect patients' feelings. As the largest multi-center, randomized, double-blind, placebo parallel-controlled, international standard clinical study of TCM, the first clinical efficacy study of TCM with cardiac and cerebrovascular events as the primary endpoint, and the first clinical safety study of TCM with placebo control and 24-month follow-up, the MUST study can be regarded as a milestone in evidence-based research in TCM. Taking the MUST study as a starting point, it is expected that more proprietary Chinese medicines will be able to carry out evidence-based studies with larger sample sizes, longer follow-up time and more complete endpoint indicators, so as to open the road to the evidence-based development of the modernization and internationalization of traditional Chinese medicine in mainland China.
brief summary
Legal security
Professor Wu Zonggui of the Second Affiliated Hospital of the Naval Medical University (Shanghai Changzheng Hospital) pointed out in his comments that the research of Musk Baoxin Pill MUST "sharpened a sword in ten years", which not only proved to the world the important role of Musk Baoxin Pill in the treatment of cardiovascular diseases from the perspective of modern evidence-based medicine, but also contributed an important force to the development of promoting the modernization of traditional Chinese medicine. From A to F, the MUST research series of Musk Baoxin Pill has not stopped, and we look forward to the advent of more research results in the future weight subgroup and non-obstructive coronary heart disease, so as to better guide the standardized use of Musk Baoxin Pill in clinical practice.