Efficacy and safety of Shexiang Baoxin Pill (MUSKARDIA) in patients with stable coronary artery disease across different weight subgroups

ETHNOPHARMACOLOGICAL RELEVANCE: Shexiang Baoxin Pill (MUSKARDIA), a traditional Chinese patent medicine, plays a crucial role in both preventing and treating diverse cardiovascular diseases, including coronary heart disease, myocardial infarction (MI), and heart failure. Preclinical research has demonstrated that the cardioprotective effects of MUSKARDIA are achieved through multiple pathways, such as enhancing coronary artery dilation, fostering new blood vessel growth, reducing inflammation and oxidative stress, improving lipid metabolism, and protecting vascular endothelium. AIM OF THE STUDY: This subgroup analysis aimed to evaluate the efficacy and safety of Shexiang Baoxin Pill (MUSKARDIA) plus optimal medical therapy (OMT) across different weight categories in treating stable coronary artery disease (CAD). METHODS: This investigation was a subgroup analysis of a multicenter, randomized, double-blind, placebo-controlled phase IV clinical study. Patients receiving OMT were randomly assigned to either MUSKARDIA or placebo group for a 24-month period. This analysis focused on body weight as a distinguishing factor, using 65 kg as the cutoff. The primary efficacy endpoint was the composite of major adverse cardiovascular events (MACEs), including cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal stroke. Secondary efficacy endpoint comprised a composite of all-cause mortality, non-fatal MI, non-fatal stroke, hospitalizations for unstable angina or heart failure, and coronary revascularization procedures. RESULTS: A total of 2646 patients were included in the analysis, with 916 patients weighing less than 65 kg and 1730 patients weighing 65 kg or more. The median ages were 68 (range: 35-90) years and 62 (range: 29-90) in these two subgroups, respectively. For patients weighing less than 65 kg, the MUSKARDIA group exhibited a significantly lower incidence of the primary efficacy endpoint (0.65%) compared to the placebo group (2.64%) (P = 0.018), with a reduced risk of MACEs (HR = 0.241, 95%CI: 0.068-0.856; P = 0.0168). Conversely, in patients weighing 65 kg or more, no significant differences were observed in the incidence rates or risks of primary or secondary efficacy endpoints between the MUSKARDIA and placebo groups (All P > 0.05). Adverse events were similar between two groups across both weight subgroups. CONCLUSIONS: MUSKARDIA plus OMT demonstrated promising efficacy and acceptable safety in CAD patients weighing less than 65 kg, potentially reducing the risk of MACEs. For patients weighing 65 kg or more, further investigation is needed to optimize dosing strategies.