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From April 11 to 14, 2024, the 25th Southern Conference on Cardiovascular Diseases was held in Guangzhou. On the afternoon of April 12, Professor Lin Jinxiu, director of the Department of Cardiology of the First Affiliated Hospital of Fujian Medical University, conducted an in-depth research and interpretation of the "Efficacy and Safety of Musk Baoxin Pill in the Treatment of Patients with Stable Coronary Heart Disease and Diabetes: A Subgroup Analysis of a Randomized Clinical Trial" (MUST-D Study), and nearly 200 experts and scholars in the cardiovascular field from all over the country listened to the conference report.
麝香保心丸的循证发展之路:MUST-A到MUST-E
In 2011, Academician Ge Junbo from Zhongshan Hospital Affiliated to Fudan University and Professor Fan Weihu from Huashan Hospital Affiliated to Fudan University conducted a large-scale evidence-based study of Musk Baoxin Pill in line with international norms, the MUST Study, which is a multicenter, randomized, double-blind, placebo-controlled phase IV trial to evaluate the clinical efficacy of Musk Baoxin Pill in combination with standard therapy in patients with stable coronary heart disease (CAD). All endpoints of this study were decided by the endpoint event review committee composed of experienced cardiovascular experts, and academician Chen Keji of Xiyuan Hospital of China Academy of Chinese Medical Sciences served as the chairman of the committee.
In January 2021, the 10-year study of Musk Baoxin Pill MUST was finally published in the Chinese Medical Journal (MUST-A). The results of the study showed that the risk of major adverse cardiovascular events (MACE) was reduced by 26.9% in the Musk Baoxin pill group compared with the placebo group, and the incidence of angina pectoris in patients with stable CAD was significantly reduced after 24 months of treatment with Musk Baoxin pill, and it had a good safety profile. In April 2021, witnessed by more than 60,000 experts and scholars across the country, the results of the MUST study were officially released (MUST-B). In June 2022, the "Expert Consensus on the Treatment of Coronary Heart Disease with Musk Baoxin Pills" was released (MUST-C). In 2023, with the in-depth excavation of the results of the MUST study, the results of the diabetes subgroup analysis (MUST-D) and pharmacoeconomic study (MUST-E) of the Musk Baoxin Pill MUST study will also be released one after another.
MUST-D: Musk Baoxin Pill provides a "new weapon" for the treatment of patients with coronary heart disease and diabetes
Professor Lin pointed out in the report that when CAD and diabetes coexist, cardiovascular lesions are more widespread and severe, and there are microangiopathies and vascular wall inflammation, which will increase the risk of myocardial infarction and death in patients. Theoretically, the combination of traditional Chinese and Western medicine in the treatment of CAD complicated with diabetes mellitus may play a multi-target and multi-role role in coronary heart disease A (antiplatelet suppressant, etc.), B (β receptor blockers, etc.), C (regulating blood lipids), D (hypoglycemia, diet), and E (exercise and patient education), combined with the multi-target and multi-effect of Musk Baoxin Pill (which plays a role in dilating coronary arteries, improving endothelial function, inhibiting vascular wall inflammation, and promoting therapeutic angiogenesis). Based on this, the MUST-D study aims to evaluate the efficacy and safety of Musk Baoxin Pill in patients with CAD and diabetes.
The MUST-D study was based on data from 97 research centers in the MUST study, and subgroup data from patients with CAD and diabetes mellitus were analyzed. The results of the study were officially published in Chinese Medical Journal in January 2023, with an impact factor of 6.133.
Based on the MUST study, MUST-D conducted subgroup analyses of patients with CAD and diabetes mellitus (with a history of diabetes or fasting blood glucose ≥7 mmol/L) and patients with diabetes mellitus with CAD with poor glycemic control (at least 4 fasting blood glucose measurements ≥7 mmol/L in 5 follow-ups), with the primary endpoint being the occurrence and improvement of the primary cardiovascular event (MACE, a composite outcome of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke), and the secondary endpoint being all-cause death, Occurrence and improvement of composite outcomes of non-fatal myocardial infarction, non-fatal stroke, hospitalization for unstable angina pectoris or heart failure, and coronary angioplasty, with the safety endpoint being the occurrence of adverse events and serious adverse events during the 24-month treatment period.
The results showed that for patients with diabetes mellitus with CAD, the incidence of MACE in the Musk Baoxin pill group was 45.8% lower than that in the placebo group at 24 months, and the incidence of secondary endpoint events was 32.3% lower than that in the placebo group (P=0.017), and for patients with diabetes 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); The incidence of various adverse events of long-term use of Musk Baoxin Pill was comparable to that of 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.
In the discussion, Professor Lin pointed out that the results of relevant basic studies have shown that Musk Baoxin Pill can increase the expression level of 20-hydroxy-eicosanetetraenoic acid (20-HETE) in patients, repair myocardial infarction area, and restore vascular endothelial function. In addition, Musk Baoxin Pill can also activate PI3K and MAPK signaling pathways to promote angiogenesis at the infarct injury site, protect microvascular endothelial cells and improve vascular endothelial function through ALDH2/AKT/mTOR signaling pathway, and inhibit inflammation of blood vessel wall and stabilize plaque. This multi-target mechanism of action may be the basis for its good efficacy.
At the same time, Professor Lin also said that there are still some limitations in the MUST-D study, such as the relatively short follow-up time of two years and the relatively insufficient number of cases, which cannot fully reflect the efficacy and safety of Musk Baoxin Pill after a longer period of time. In addition, since this study was initiated more than 10 years ago, the blood glucose monitoring indicators of diabetic patients can be optimized, and if glycosylated hemoglobin is selected, it can more objectively reflect the average level and overall trend of blood glucose. Finally, this is a subgroup analysis rather than a randomized controlled trial in patients with stable CAD and diabetes, which may be subject to selection bias and should be interpreted to account for the lack of covariate adjustments.
brief summary
Microcirculatory disorder is one of the important pathophysiological bases of diabetes, and the combination of diabetes in CAD patients will further affect the microcirculation function, aggravate myocardial dysfunction, and lead to death in severe cases. The MUST-D study confirmed the potential and effectiveness of Musk Baoxin Pill in combination with standard therapy in the treatment of patients with stable CAD and diabetes. This study not only improves our understanding of the combination of traditional Chinese and Western medicine in the treatment of coronary heart disease, but also provides important data support for future clinical application and further research directions.