Yin Jiang, Xiao-Yu Zhang, Gui-Hua Tian, Li-Jing Zhang, Ming-Xue Zhang, Hai-Tong Wan, Min Ye, Rong-Rong He, Xin Sun, Hong-Cai Shang*

1Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital affiliated to Beijing University of Chinese Medicine, Beijing, China. 2 Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Liaoning, China. 3 Zhejiang Chinese Medical University, Zhejiang, China. 4 Peking University, Beijing, China.5 Jinan University, Guangdong, China. 6 Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Sichuan, China.

Coronary heart disease (CHD) seriously endangers public health. The data ofChina Cardiovascular Disease Report 2017indicates that the number of CHD patients in China had increased to 11 million. The death rate of CHD in urban and rural residents in China was about 110/10 thousands [1]. Progressively, patients with CHD will develop angina pectoris, myocardial infarction, and ischemic heart failure. At present, Western medicine has committed itself to measures of controlling risk factors,secondary prevention, cardiac rehabilitation, as well as surgical intervention. It has played an important role in delaying disease progression and reducing morbidity and mortality. However, there are still many intricate problems in clinical practice. For example, it is hard to alleviate recurrent angina; there are microvascular dysfunction, ischemia-reperfusion injury, in-stent restenosis and thrombosis after percutaneous coronary intervention; heart failure patients have to face multiple complications, repeated hospital admission and poor quality of life, etc. For such clinically progressive cardiovascular diseases, traditional Chinese medicine(TCM) can take the advantages of multi-level regulation and acting on multiple targets. TCM can exert effects of prevention and treatment, interfering with disease progression, which has been widely used in clinical practice. Therefore, there is great potentiality to integrate traditional Chinese and Western medicine therapies to prevent and treat CHD [2]. However, the current integrated therapies still lack sufficient high-quality evidence, and the key links in how to apply are unclear. It is urgent to optimize them through evidence-based research to further improve the effectiveness.

The national key research and development project"Evidence-based optimization research of TCM therapies in prevention and treatment of CHD (angina pectoris -myocardial infarction - heart failure)" is aimed at solving the above problems. The design methods and implementation details were seriously considered. We proposed a joint research on the prevention and treatment of progressive diseases. It was supposed to preliminarily clarify the evidences of three integrated Chinese and Western medicine therapies for prevention and treatment on clinically appropriate population, the timing of intervention, and the effect of long-term prognosis. At the same time, exploring the biological basis of the TCM syndrome and the mechanism of drug action during the disease progression.

Integrated clinical trial design

In CHD, angina pectoris - myocardial infarction -ischemic heart failure can be seen as a developing process.The outcome of the last disease patients are the research objects of the next disease, establishing a master protocol framework which integrates three randomized controlled trials. Based on the master protocol design, a number of clinical trials share common research centers, and digital integration management platform with the intention to achieve resource integration and information sharing, as much as possible to save clinical research resources and improve research efficiency. The master protocol design provides methodological support for TCM clinical trials studying different diseases. It not only provides joint evidence of TCM therapies for treatment and prevention,but also fits the research purpose of studying the common TCM syndrome of various diseases, which is conducive to explore the underlying mechanism of TCM intervention and syndrome. It provides the possibility for further in-depth research [3].

Attention to the key links of taking effect

Many integrated traditional Chinese and Western medicine therapies have been applied for many years in clinical practice. However, the suitable population for application, the timing of intervention and the long-term effects are not clear enough. Most of the existing guidelines for integrated traditional Chinese and Western medicine are lack of relevant evidence and recommendations [4]. Therefore, it is necessary to further explore the suitable population, the optimal intervention timing and the impact on long-term prognosis in addition to verifying the efficacy of the treatment. For example,we use a practical randomized controlled trial design in the "evidence-based optimization study of TCM syndrome differentiation treatment on angina pectoris"project, which applies adjusted Danlou prescription to classified patients with phlegm and blood stasis syndrome.In the “evidence-based optimization of TCM treatment for myocardial infarction in perioperative period of percutaneous coronary intervention” project, the effect of Danhong loading therapy is evaluated, and the best intervention timing during perioperative period of percutaneous coronary intervention is explored [5].

Combination of clinical and basic research

The integration of traditional Chinese and Western medicine needs mutual participation of clinical and basic research. The clinical master protocol design also provides the necessary conditions for clinical basic integration research. As progressive cardiovascular disease has a common vascular pathological basis and TCM pathogenesis of “deficiency-phlegm-blood stasis”,systematic studies can be carried out using biological samples collected in clinical trials, combined with animal,cell, and molecular experiments. We can start with the whole biological process of pathological changes to clarify the scientific connotation of traditional Chinese medicine intervention for coronary heart disease,screening biomarkers of TCM syndrome, elucidating the pharmacodynamic substances and in vivo metabolic process of the TCM prescriptions, as well as the synergy mechanism of the compounds [6].

Based on the above strategies, we started the researches on the integrated traditional Chinese and Western medicine therapies to prevent and treat CHD (angina pectoris, myocardial infarction and ischemic heart failure),which are expected to be a new paradigm for the design and implementation of evidence-based optimization of integrated traditional Chinese and Western medicine therapies for prevention and treatment in the field.

1. Chen WW, Gao RL, Liu LS, et al. Summary of"China Cardiovascular Disease Report 2017". China J Circ 2018, 33: 1-8.

2. Bi YF, Mao JY, Wang XL, et al. Clinical Advantages of Traditional Chinese Medicine for Prevention and Treatment of Coronary Heart Disease and Relevant Efficacy Evaluation. J Tradi Chin Med 2015, 56:437-440.

3. Zhao C, Zhang XY, Hu JY, et al. Design method of clinical research for clinical research of syndromes in Chinese medicine. J Tradi Chin Med 2018, 59:111-115.

4. Yao L. Research on Methodology Quality of Clinical Practice Guide for Traditional Chinese Medicine D.Lanzhou University, 2016.

5. Cheng CW, Wu TX, Shang HC, et al. CONSORT Extension for Chinese Herbal Medicine Formulas 2017: Recommendations, Explanation, and Elaboration. Ann Intern Med 2017, 167: 112-121.

6. Qiao X, Guo D, Ye M. Recent Methods and Strategies for in vivo Metabolic Study of Traditional Chinese Medicines. Mod Tradi Chin Med Materia Medica-World Sci Technol 2014, 16: 532-537.