Effects of adjuvant Chinese patent medicine therapy on major adverse cardiovascular events in patients with coronary heart disease angina pectoris: a population-based retrospective cohort study

Abstract

Objective: This study aimed to explore the effects of Chinese patent medicine (CPM) in reducing the incidence of major adverse cardiovascular events (MACE) in patients with coronary heart disease (CHD) angina pectoris and improving clinical effectiveness and provide evidence for its use as clinical adjuvant therapy.
Methods: Twenty-eight thousand five hundred and seventeen patients hospitalized with CHD angina pectoris from 6 hospitals were divided into CPM group (n = 11,374) and non-CPM group (n = 17,143) to evaluate the incidence of MACE, including myocardial infarction, percutaneous coronary intervention, and coronary artery bypass grafting.
Results: The incidence of MACE in the CPM group was lower than that in the non-CPM group. CPM therapy was an independent protective factor that reduced the overall risk of MACE [adjusted hazard ratio = 0.40, 95% confidence interval (0.33; 0.49)]. Patients in the CPM group who received one, two, or three types of CPM could benefit from adjuvant treatment with CPM, and taking more types of CPM was associated with a lower risk of MACE. In addition, the male population was better than the female population in taking CPM, and middle-aged people aged 55 to 64 were more suited to take CPM based on Western medicine.
Conclusions: The use of CPM as adjuvant therapy can decrease the occurrence of MACE in patients with CHD angina pectoris, especially in men and middle-aged people, and the drug treatment plan should be optimized accordingly. However, this conclusion needs further verification by prospective cohort studies in the future.

Keywords

Chinese patent medicine / Coronary heart disease angina pectoris / Major adverse cardiovascular events / Retrospective cohort study

Conflict of interest statement

The authors declare no conflict of interest.

Funding

This work was supported by the National Basic Research Program of China (973 project, grant number: 2014CB542902) and Tianjin Hongrentang Pharmaceutical Co., Ltd., Tianjin, China (grant number: HX2020-16).

Author contributions

Thanks for the conceptualization and methodology of Mingchi Luo and Yijia Liu, the data curation of Rongrong Yang, Yijia Liu, Zhu Li, Xu Wang, Mei Ma, Yuanyuan He, and Tongyao Ni, the investigation of Yijia Liu, Zhu Li, Xu Wang, the writing-original draft preparation and visualization of Yijia Liu, the writing – reviewing and editing of Rongrong Yang and Mingchi Luo.

Ethical approval of studies and informed consent

This study was approved by the Ethics Committee of Tianjin University of Traditional Chinese Medicine (Lot Number: TJUTCM-EC20190008), and the requirement for informed consent was waived. It has been registered in the Clinical Trials.gov (registration number: NCT04026724) and the Chinese Clinical Trial Registry (registration number: ChiCTR1900024535).

Acknowledgements

We would like to thank Professor Kaijun Niu of Tianjin Medical University for his guidance on this study, as well as Director Xianliang Wang of First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Director Qiang Xu of Second Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Director Chunjie Li of Tianjin Chest Hospital, Director Sheng Gao of Nankai Hospital: Tianjin Hospital of Integrated Traditional Chinese and Western Medicine, Director Hongmei Zheng of Tianjin Medical University General Hospital and Director Ruihong Fan of Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital provided case data for this study.

References

[1] Arnett DK, Blumenthal RS, Albert MA, et al.2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2019;140(11):e596-e646.

[2] Yang S, Li X, Yang F, et al.Gut microbiota-dependent marker TMAO in promoting cardiovascular disease: inflammation mechanism, clinical prognostic, and potential as a therapeutic target. Front Pharmacol 2019;10:1360.

[3] GBD 2017 Causes of Death CollaboratorsGlobal, regional, national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017.BD 2017 Causes of Death CollaboratorsGlobal, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018;392(10159):1736-1788.

[4] Cavus E, Karakas M, Ojeda FM, et al.Association of circulating metabolites with risk of coronary heart disease in a European population: results from the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) Consortium. JAMA Cardiol 2019;4(12):1270-1279.

[5] Anderson JL, Adams CD, Antam EM, et al.ACC/AHA 2007 guidelines for the management of patients with unstable angina/ non-ST-Elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction): developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons: endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. Circulation 2007;116(7):e148-e304.

[6] Zhang Y, Xie Y, Liao X, et al.A Chinese patent medicine Salvia miltiorrhiza depside salts for infusion combined with conventional treatment for patients with angina pectoris: a systematic review and meta-analysis of randomized controlled trials. Phytomedicine 2017;25:100-117.

[7] Balla C, Pavasini R, Ferrari R.Treatment of angina: where are we? Cardiology 2018;140(1):52-67.

[8] Joshi PH, de Lemos JA. Diagnosis and management of stable angina: a review. JAMA 2021;325(17):1765-1778.

[9] Liu X, Li M, Wang X, et al.Effects of adjuvant traditional Chinese medicine therapy on long-term survival in patients with hepatocellular carcinoma. Phytomedicine 2019;62:152930.

[10] Yang J, Tian S, Zhao J, et al.Exploring the mechanism of TCM formulae in the treatment of different types of coronary heart disease by network pharmacology and machining learning. Pharmacol Res 2020;159:105034.

[11] The Ministry of Health released the 2012 edition of the Chinese National Essential Drug. Available from: the 2012 edition of the Chinese National Essential Drug. Available from: . Available from: the 2012 edition of the Chinese National Essential Drug. Available from: Updated March 15, 2013. Accessed February 11, 2022.

[12] Chinese Pharmacopoeia CommissionPharmacopoeia of People's Republic of China[S] Chinese Pharmacopoeia CommissionPharmacopoeia of People's Republic of China[S]. Part 1. Beijing: China Medical Science Press; 2020.

[13] Hu Z, Wang H, Fan G, et al.Danhong injection mobilizes endothelial progenitor cells to repair vascular endothelium injury via upregulating the expression of Akt, eNOS and MMP-9. Phytomedicine 2019;61:152850.

[14] Cao H, Wang P, Li N, et al.Practice of comparative effectiveness research to identify treatment characteristics of similar chinese patent medicine for angina pectoris. Evid Based Complement Alternat Med 2017;2017:7062714.

[15] Thivalapill N, Lockman S, Powis K, et al.Are morbidity and mortality estimates from randomized controlled trials externally valid? A comparison of outcomes among infants enrolled into an RCT or a cohort study in Botswana. BMC Med Res Methodol 2021;21(1):212.

[16] Pan A, Lin X, Hemler E, Hu FB.Diet and cardiovascular disease: advances and challenges in population-based studies. Cell Metab 2018;27(3):489-496.

[17] Hao P, Jiang F, Cheng J, et al.Traditional Chinese medicine for cardiovascular disease: evidence and potential mechanisms. J Am Coll Cardiol 2017;69(24):2952-2966.

[18] Jia Q, Wang L, Zhang X, et al.Prevention and treatment of chronic heart failure through traditional Chinese medicine: role of the gut microbiota. Pharmacol Res 2020;151:104552.

[19] Spatz ES, Wang Y, Beckman AL, et al.Traditional Chinese medicine for acute myocardial infarction in Western medicine hospitals in China. Circ Cardiovasc Qual Outcomes 2018;11(3): e004190.

[20] Li J, Cao GY, Zhang XF, et al.Chinese medicine She-Xiang-Xin- Tong-Ning, containing Moschus, Corydalis and Ginseng, protects from myocardial ischemia injury via angiogenesis. Am J Chin Med 2020;48(1):107-126.

[21] Huang J, Tang X, Ye F, et al.Clinical therapeutic effects of aspirin in combination with Fufang Danshen Diwan, a traditional Chinese medicine formula, on coronary heart disease: a systematic review and meta-analysis. Cell Physiol Biochem 2016;39(5):1955-1963.

[22] Zhang GX, Zhang YY, Zhang XX, et al.Different network pharmacology mechanisms of Danshen-based Fangjis in the treatment of stable angina. Acta Pharmacol Sin 2018;39(6):952-960.

[23] Hua Z, Zhai FT, Tian J, et al.Effectiveness and safety of oral Chinese patent medicines as adjuvant treatment for unstable angina pectoris on the national essential drugs list of China: a protocol for a systematic review and network meta-analysis. BMJ Open 2019;9(9):e026136.

[24] Wang D, Li C, Xu X, et al.Effect of Yugengtongyu granules in patients with stable coronary artery disease on reducing adverse cardiovascular events: a double-blind controlled trial. J Altern Complement Med 2021;27(2):142-149.

[25] Li W, Wu Y, Wan M, et al.Simultaneous determination of three saponins in human plasma after oral administration of compound danshen dripping pills by LC-MS/MS and its application in a pharmacokinetic study. J Pharm Biomed Anal 2019;169:254-259.

[26] Wu X, Han X, Li L, et al.iTRAQ-based quantitative proteomics and target-fishing strategies reveal molecular signatures on vasodilation of Compound Danshen Dripping Pills. Chem Biol Interact 2020;316:108923.

[27] Han JY, Li Q, Ma ZZ, et al.Effects and mechanisms of compound Chinese medicine and major ingredients on microcirculatory dysfunction and organ injury induced by ischemia/reperfusion. Pharmacol Ther 2017;177:146-173.

[28] Long F, Yang H, Xu Y, et al.A strategy for the identification of combinatorial bioactive compounds contributing to the holistic effect of herbal medicines. Sci Rep 2015;5:12361.

[29] Liao W, Ma X, Li J, et al.A review of the mechanism of action of Dantonic^®for the treatment of chronic stable angina. Biomed Pharmacother 2019;109:690-700.

[30] Fan Y, Liu J, Miao J, et al.Anti-inflammatory activity of the Tongmai Yangxin pill in the treatment of coronary heart disease is associated with estrogen receptor and NF-kB signaling pathway. J Ethnopharmacol 2021;276:114106.

[31] Chen R, Chen T, Wang T, et al.Tongmai Yangxin pill reduces myocardial No-reflow via endothelium-dependent NO-cGMP signaling by activation of the cAMP/PKA pathway. J Ethnopharmacol 2021;267:113462.

[32] Chen R, Chen T, Wang T, et al.Tongmai Yangxin pill reduces myocardial no-reflow by regulating apoptosis and activating PI3K/ Akt/eNOS pathway. J Ethnopharmacol 2020;261:113069.

[33] Cui Y, Li C, Zeng C, et al.Tongmai Yangxin pills anti-oxidative stress alleviates cisplatin-induced cardiotoxicity: network pharmacology analysis and experimental evidence. Biomed Pharmacother 2018;108:1081-1089.

[34] Cai X, Du J, Li L, et al. Clinical metabolomics analysis of therapeutic mechanism of Tongmai Yangxin pill on stable angina. J Chromatogr B Analyt Technol Biomed Life Sci 2018; 1100-1101:106-112.

[35] Zhang T, He WT, Zi MJ, et al.Cohort study on prognosis of patients with metastatic colorectal cancer treated with integrated Chinese and western medicine. Chin J Integr Med 2018;24(8):573-578.

[36] Peters SAE, Colantonio LD, Dai Y, et al.Trends in recurrent coronary heart disease after myocardial infarction among US women and men between 2008 and 2017. Circulation 2021;143(7):650-660.

[37] Diaz-Canestro C, Pentz B, Sehgal A, et al.Sex differences in cardiorespiratory fitness are explained by blood volume and oxygen carrying capacity. Cardiovasc Res 2022;118(1):334-343.

[38] Connelly PJ, Azizi Z, Alipour P, et al.The importance of gender to understand sex differences in cardiovascular disease. Can J Cardiol 2021;37(5):699-710.

[39] Rawshani A, Sattar N, Franzén S, et al.Excess mortality and cardiovascular disease in young adults with type 1 diabetes in relation to age at onset: a nationwide, register-based cohort study. Lancet 2018;392(10146):477-486.

[40] Jeon YW, Bang HW, Suh YJ, et al.The long-term effect of age on cardiovascular disease in patients with breast cancer who received chemotherapy. Breast Cancer Res Treat 2020;180(3):665-674.

[41] Lind L, Ingelsson E, Sundström J, et al.Methylation-based estimated biological age and cardiovascular disease. Eur J Clin Invest 2018;48(2):e12872.