According to the Global Burden of Disease Report 2021, from 1990 to 2021, ischemic heart disease has always ranked first in the global mortality rate, and the global disability-adjusted life years increased from 159.9 million to 188.3 million (GBD, 2021 Causes of Death Collaborators et al., 2024; GBD, 2021 Diseases and Injuries Collaborators, 2024). The American Heart Association’s Heart and Stroke Statistics Report 2024 shows that, based on the data from the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020, the overall prevalence of cardiovascular disease (CVD) among adults aged 20 and above in the United States is 7.1%, and the overall prevalence of angina pectoris is 3.9% (Martin et al., 2024). The China HEART study adopted the ABM (Agent-Based Model) model to predict that by 2030, the incidence rate of CVD will rise from 0.74% in 2021 to 0.97% (Wang et al., 2025), and the mortality rate is expected to increase from 0.39% in 2021 to 0.46% in 2024. CVD remain the primary burden on China’s medical and health care. Stable angina pectoris (SAP) is a symptom of chest pain caused by insufficient blood supply in the coronary arteries based on fixed stenosis of the coronary arteries. It is often manifested as a crushing pain or a feeling of suffocation, with a short duration, and can be induced by exercise, emotional fluctuations, or other stress factors, and it can be relieved by rest or taking nitrates (Joshi and de Lemos, 2021). The treatment principles of SAP in Western medicine mainly focus on improving prognosis and relieving symptoms. In clinical practice, lipid-lowering drugs and antiplatelet drugs are commonly used to prevent adverse cardiovascular events, and beta-blockers, nitrates, or calcium channel blockers are used to improve the symptoms of angina pectoris.

In the field of Traditional Chinese medicine (TCM), SAP belongs to the category of “chest paralysis and heartache”, and its pathogenesis is summarized as “yang and micro yin strings” in the “Synopsis of the Golden Chamber”, that is, the yang in the chest is sluggish, and the cold yin invades internally, resulting in heart and pulse paralysis, it reveals that this disease belongs to the pattern of deficiency in origin and excessiveness in manifestation (O’Brien and Vitetta, 2012; Zhang et al., 2014). Regarding the distribution of syndromes, some scholars have found through data mining that SAP commonly presents with syndromes such as qi deficiency and blood stasis, intermingling of phlegm and blood stasis, and qi stagnation and blood stasis. The main treatment methods are promoting blood circulation to remove blood stasis, regulating qi to relieve stagnation, resolving phlegm and lowering turbidity, and replenishing qi to dredge the meridians (Ying et al., 2021; Liu and Huang, 2016).

With the development of medicine, TCM is widely used to treat angina pectoris, effectively improving the clinical symptoms and prognosis of patients. As early as 2020, CVD was listed as one of the dominant diseases in the treatment of proprietary Chinese medicines in the Guidelines for the Clinical Application of Proprietary Chinese Medicines in the Treatment of Dominant Diseases. Yingxin pill (YXP) has the effect of nourishing the heart and pulse, removing blood stasis, and relieving pain, it can improve myocardial ischemia and alleviate the symptoms of angina. To further clarify the clinical value of YXP, this study adopted a non-inferiority design and selected Shexiang Baoxin Pill (SBP), a widely recognized agent for SAP that has been validated by large-scale clinical trials, as the positive control (Wei et al., 2022; Wang et al., 2021; Ge et al., 2021). It aimed to systematically evaluate the efficacy of YXP combined with conventional Western medicine in the treatment of stable angina pectoris and to explore its effects on inflammatory indicators and blood lipid levels. By demonstrating the non-inferiority of YXP, the findings are intended to support its potential as an alternative treatment option, thereby expanding therapeutic choices for clinicians and patients.

As the aging process of China’s population accelerates, the incidence of CVD, especially angina pectoris events, has been increasing year by year, and the corresponding disease burden has been growing heavier day by day (Qu et al., 2024; Li et al., 2023). Currently, it has become a major health problem affecting the country, society, and individuals. At present, the primary goals of the treatment for angina pectoris are to improve myocardial blood supply and prognosis and to enhance the quality of life by reducing the symptoms of angina pectoris. These goals can be achieved through improving lifestyle, using preventive medications, and selectively applying coronary revascularization (Montone et al., 2024). The preventive medications commonly used in clinical practice to reduce the incidence of angina pectoris mainly include beta-blockers, calcium channel blockers, lipid-lowering drugs, antiplatelet drugs, nitrates, and so on (Zhang et al., 2023; Grundy et al., 2019). Although there is a wide variety of existing medications for the treatment of angina pectoris, it is still nitrates that can quickly relieve the immediate symptoms of angina pectoris. The choice of medications is rather limited (Virani et al., 2023). Therefore, it is of positive significance to seek more effective ways to relieve symptoms and increase the available treatment options.

This study provides preliminary yet important clinical evidence for the use of YXP in combination with conventional Western medicine in patients with SAP. In this randomized, non-inferiority, active-controlled trial, the intervention achieved a modest but statistically significant improvement—measured primarily by the SAQ—compared with standard therapy alone. The combination treatment was well tolerated, with no serious adverse events observed during the study period. Our results align with the growing body of evidence indicating the unique advantages of TCM in the treatment of angina pectoris. By acting on multiple targets and through numerous pathways, TCM interventions may alleviate angina symptoms, improve exercise tolerance, and enhance quality of life (Tian et al., 2024). Although our study has been limited by methodological weaknesses, the available literature suggests that similar Chinese botanical drug formulas can help relieve angina symptoms, improve quality of life, and enhance prognosis, indicating that integrative approaches combining Western and traditional medicine may confer additional benefits over conventional treatment alone.

From the perspectives of clinical service and evidence-based practice, our study highlights the importance of scientifically evaluating traditional medicine based on modern clinical research standards. Incorporating proven-effective traditional therapies into modern healthcare systems could expand therapeutic options for SAP, particularly for patients who are intolerant of or have limited access to Western pharmaceuticals. However, because this was a small-scale, non-inferiority trial, the reliability of the findings may be limited, as slight biases or random variations could easily influence the results. Therefore, our study should be regarded as a pilot trial. Further randomized controlled studies with larger samples, multicenter design, double-blinding, longer follow-up, and major cardiovascular and quality-of-life endpoints are essential to confirm our findings and clarify their generalizability.

From a mechanistic perspective, the pharmacological effects of YXP are attributed to a spectrum of bioactive metabolites derived from its constituent botanical drugs, such as ginsenosides (from Panax ginseng), bufadienolides (from Bufonis Venenum), eugenol (from Syzygium aromaticum), and bile acids (from Suis Fellis Pulvis). These metabolites exhibit complex synergistic pharmacological actions, including vasodilation, improvement of endothelial function, anti-inflammatory, and antioxidative properties (Kim, 2018; Wei et al., 2023; Lee et al., 2002). Compared with SBP, the main difference in the composition of YXP lies in the fact that it contains pig bile powder. Current research suggests that the main active metabolites in pig bile (such as bile acids, taurine, etc.) have been demonstrated to possess multiple pharmacological effects, including anti-inflammatory, lipid metabolism regulation, vascular endothelial protection, and antiplatelet aggregation (Li et al., 2022; Lefebvre et al., 2009). These modern pharmacological actions are consistent with the implications of improving microcirculation and reducing inflammatory damage in the traditional Chinese medicine theory of promoting blood circulation and removing toxins. Some of these effects have been demonstrated in basic and limited clinical studies. It is noteworthy that a growing body of evidence supports inflammation as a fundamental driver of residual risk in atherosclerotic cardiovascular disease (ASCVD), with a causal relationship to its development and progression (Hansson, 2005; Libby, , 2002). In this study, despite receiving standardized conventional Western medical treatment, the median hs-CRP level of participants at enrollment remained above the clinically recognized threshold of 1.0 mg/L, which indicates persistent residual inflammatory risk. After 1 month of combined treatment with YXP or SBP, the median hs-CRP levels in both groups decreased to below 1.0 mg/L. This change suggests that the addition of these Chinese patent medicines to standard therapy may further suppress systemic inflammation. These findings not only provide clinical evidence for the anti-inflammatory effects of both drugs in patients with stable angina pectoris but also hint at their potential value in managing residual cardiovascular inflammatory risk and improving long-term prognosis (Yu et al., 2024). As this study primarily focused on the clinical efficacy of YXP, its precise pharmacodynamic mechanisms, as well as its potential interactions with standard antianginal medications, remain to be elucidated. Future investigations employing network pharmacology, omics technologies, and mechanistic studies are warranted.

The limitations of this study should be noted. First, this study is a single-center exploratory trial with a relatively small sample size, and all patients were recruited from Dongzhimen Hospital, Beijing University of Chinese Medicine. This may limit the generalizability of the findings and introduce potential selection bias. Furthermore, as an exploratory study, the observed results may be subject to type I error risk due to multiple comparisons. Any efficacy signals identified in these analyses require validation in future large-scale confirmatory trials. Therefore, larger-scale, multi-center clinical trials are warranted to provide more robust and conclusive evidence. Secondly, due to the significant differences in color, shape, and odor between the two intervention drugs, a double-blind design could not be implemented in this study. Consequently, only a single-blind design (with blinding of participants only) was adopted. This methodological limitation may introduce performance or assessment bias. Future research should explore appropriate improvement strategies, such as employing a double-dummy technique or selecting objective hard endpoints, to mitigate this limitation. Finally, the long-term prognostic impact of the intervention requires further in-depth investigation. Future studies should aim to adopt double-blind methodologies where possible and explore the sustained effects of the treatment over extended follow-up periods.

All in all, YXP can effectively improve the clinical symptoms of patients with stable angina pectoris, reduce the blood lipid level and inflammation level of patients with angina pectoris, expand the range of medication options for clinical patients with angina pectoris, and provide new feasibility for the clinical treatment of such patients.