Front. Pharmacol. Frontiers in Pharmacology Front. Pharmacol. 1663-9812 Frontiers Media S.A. 1643611 10.3389/fphar.2025.1643611 Pharmacology Systematic Review The clinical efficacy of herbal medicines containing leeches in the treatment of coronary heart disease: a systematic review and meta-analysis Ziyuan et al. 10.3389/fphar.2025.1643611 Ziyuan Zhao 1 Di Ye 1 Mei Liang 1 Yujing Jin 1 Jinghui Zheng 1 2 * 1 Graduate School, Guangxi University of Chinese Medicine, Nanning, Guangxi, China 2 Ruikang Hospital affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China

Edited by: Javier Echeverria, University of Santiago, Chile

Reviewed by: Mohammed Ahmed Akkaif, QingPu Branch of Zhongshan Hospital Affiliated to Fudan University, China

Sachinkumar Gunjal, Amrutvahini College of Pharmacy, India

 *Correspondence: Zheng Jinghui, jinghuizheng@yeah.net 17 10 2025 2025 16 1643611 10 06 2025 12 09 2025 Copyright © 2025 Ziyuan, Di, Mei, Yujing and Jinghui. 2025 Ziyuan, Di, Mei, Yujing and Jinghui

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 Background

Coronary heart disease (CHD) is a leading global cause of mortality, contributing to angina, arrhythmia, myocardial infarction, heart failure, and sudden death. Traditional treatments, including antiplatelet drugs, statins, β-blockers, and coronary stents, have notable side effects such as gastrointestinal bleeding and liver or muscle dysfunction, with post-operative stent complications. Recent studies have identified bioactive substances in leeches, particularly the natural anticoagulant hirudin, which inhibits thrombin and may help mitigate complications of coronary artery disease. Hirudin inhibits thrombin, reduces platelet aggregation, and lowers thrombosis risk. This meta-analysis evaluates the clinical efficacy and safety of Chinese herbal medicines containing leech in treating CHD, focusing on cardiovascular outcomes and adverse events.

 Methods

A systematic search of databases including PubMed, EMBASE, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), WanFang Data (Wanfang), and VIP China Science and Technology Journal Database (VIP) was conducted to identify randomized controlled trials (RCTs) involving leech-containing Chinese herbal medicines for CHD patients up until February 2025. Key efficacy outcomes analyzed were total effective rate, ECG efficacy, and hemorheological parameters, while adverse event rates assessed treatment safety. The meta-analysis used Standardized Mean Difference (SMD) and 95% confidence intervals (CI) to assess efficacy, and Odds Ratio (OR) with 95% CI for safety. Subgroup analyses examined the relationship between therapeutic effects and patient characteristics.

 Results

Sixty-five studies involving 7,221 patients were included. The results showed that leech-based treatments significantly improved the total effective rate [OR = 3.70, 95% CI (3.19, 4.31), Z = 17.05, P < 0.00001] and ECG efficacy [OR = 2.58, 95% CI (2.23, 2.99), P < 0.0001], along with significant improvements in hemorheological parameters. Subgroup analysis indicated leech treatments were particularly effective for improving the total effective rate, ECG outcomes, and hemorheological indices. Importantly, adverse event rates did not increase compared to conventional treatments.

 Conclusion

Chinese herbal medicines containing leeches provide significant clinical benefits for CHD, particularly in improving ECG outcomes and blood parameters. These findings suggest that leech-based treatments are both effective and safe, with no increase in adverse events.

 Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, Identifier CRD42024564675.

 coronary heart disease leech Chinese herbal medicine meta-analysis systematic review section-at-acceptance Ethnopharmacology 1 Introduction

Coronary heart disease is primarily caused by atherosclerosis or functional abnormalities in the coronary arteries, leading to myocardial ischemia, hypoxia, and necrosis. The disease’s primary clinical manifestations include angina pectoris, arrhythmia, and myocardial infarction (Pothineni et al., 2017). As one of the leading causes of global mortality, CHD accounts for approximately 9.31 million deaths annually, or nearly half of all cardiovascular disease-related deaths (Katta et al., 2021). The management of CHD typically involves antiplatelet agents, lipid-lowering drugs, β-blockers, and coronary stent implantation. However, these treatments are not without limitations, as prolonged use of these drugs can lead to adverse effects such as gastrointestinal bleeding, muscle and liver dysfunction, and complications from stent implantation (Passacquale et al., 2022; Mao et al., 2021; Zhang et al., 2024; Xin et al., 2023; Shan-Shan and Lu, 2022).

In light of the potential drawbacks of conventional therapies, recent research has focused on alternative treatments derived from traditional Chinese medicine (TCM) (Chunmiao et al., 2024). Substances in leeches, particularly hirudin, have garnered attention for their anticoagulant, anti-inflammatory, and fibrinolytic properties (Wu et al., 2024; Junren et al., 2021; Lemke and Vilcinskas, 2020). Hirudin directly inhibits thrombin activity, reduces platelet aggregation, and improves vascular health. Many randomized controlled trials have examined the efficacy of Chinese patent medicines containing leech components for treating CHD. However, no comprehensive comparison of the efficacy of different leech-containing medicines have been conducted. This study aims to bridge this gap by conducting a meta-analysis of RCTs to compare the efficacy and safety of these treatments.

 2 Materials and methods

This meta-analysis was conducted in accordance with the PRISMA guidelines of the Cochrane Handbook and was registered on the PROSPERO website. The registration number (CRD42024564675).

2.1 Search strategy

A systematic search was performed across multiple key medical databases, including PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, and VIP, covering publications from their inception until February 2025. Keywords such as “Leeches,” “Coronary Disease,” “Angina,” “Heart Disease,” “Acute Coronary Syndromes,” and “Randomized Controlled Trial (RCT)” were used to identify relevant studies. In addition, experts in the field were consulted to gather unpublished data and ensure a comprehensive search. Detailed search formula table is attached as an appendix.

 2.2 Study selection

The studies were screened according to the PICOS framework. Eligible studies included RCTs evaluating the efficacy of Chinese herbal medicines containing leech components in CHD patients. Studies were excluded if they did not clearly mention the use of leech components, had incomplete data, or lacked scientific rigor (Table 1).

Inclusion and exclusion criteria table.

Parameter Inclusion criteria
Population Patients with a definite diagnosis of coronary heart disease (diagnostic criteria were in accordance with relevant domestic and foreign guidelines) were enrolled
Intervention Chinese herbal medicines containing leech ingredients were used alone or in combination with conventional treatment
Comparator Conventional treatment, placebo or other Chinese medicine;
Outcome The improvement rate of angina symptoms, electrocardiogram improvement rate, hemorheology index, incidence of major cardiovascular events and adverse drug reactions were recorded.
Study design Being an RCT in either parallel or cross-over design
Exclusion criteria Non-RCT studies, those not clearly mentioning the components of leeches, incomplete data or inability to extract valid data, studies with a follow-up period shorter than 4 weeks or lacking scientific evidence, as well as low-quality studies that have been repeatedly published.

This meta-analysis aims to evaluate the efficacy and safety of traditional Chinese medicines containing leech in the treatment of CHD by including high-quality RCTs. The inclusion criteria focus on studies with clear diagnostic standards for CHD, encompassing patients of any age or sex with stable or unstable angina. The interventions include the use of leech-containing traditional Chinese medicine, either as monotherapy or combined with conventional western medicine, compared with control groups receiving standard treatments, placebo, or TCM without leech. Key outcomes are categorized into primary outcomes, such as angina relief rate and ECG improvement rate, and secondary outcomes, including hemorheology and cardiac function indexes, incidence of major cardiovascular events, and drug-related adverse reactions. To ensure reliability, included studies must provide a clear description of randomization, control settings, and intervention measures, along with complete baseline data, post-treatment results, and statistical analyses. This comprehensive approach aims to provide robust evidence for the role of leech-containing TCM in CHD management.

Studies were excluded from this analysis if they: (1) Non-rct studies (such as observational studies, case reports, reviews, etc.); (2) The leech component was not explicitly mentioned in the intervention; (3) Incomplete data or unable to extract valid data; (4) The duration of follow-up was less than 4 weeks or the intervention lacked scientific evidence; (5) Duplicate published studies, and only the versions with complete data or higher quality were included.

 2.3 Data extraction and quality assessment

Two investigators independently completed data extraction and cross-checked the extracted data. Disagreements were resolved through consultation or the intervention of third-party experts. The study authors; Time of publication; The sample size; Gender of the patient; Mean age; Type of disease; Primary outcome measures. If the data units are different for each parameter, we convert them to the most commonly used units.

The Cochrane Bias risk assessment tool was used to evaluate the quality of the included studies from the following six dimensions: 1. Random sequence generation (selection bias); 2. Allocation concealment (selection bias); 3. Blinded implementation (implementation bias and detection bias); 4. Data integrity (loss of follow-up bias); Selective reporting (reporting bias); 5. 6. Other sources of bias. According to the scoring results, the quality of the studies was divided into “high risk of bias”, “low risk of bias” and “uncertain risk of bias”.

Meta-analysis was performed using RevMan 5.4 software provided by Cochrane Collaboration. Relative risk difference (RD) and Mean difference (MD) were used as effect measures, and the point estimate of each effect size and its 95% confidence interval (95%CI) were reported. The test of heterogeneity was conducted by χ2 test (test level α = 0.1), and the degree of heterogeneity was evaluated by I2 statistic. Considering the possible statistical heterogeneity between studies, a random-effects model was used to integrate the results of various studies more accurately. In addition, funnel plots were used to assess the possibility of publication bias during the analysis of effect measures.

 3 Results 3.1 Results of literature search

A total of 1,342 studies were initially retrieved, and after removing duplicates and screening titles and abstracts, 97 studies were shortlisted for full-text review as shown in Figure 1. Ultimately, 65 studies (Wu et al., 2001; Tong et al., 2001; Zhongtian and Rihui, 2001; Jian and Xudong, 2002; Jing et al., 2002; Taojin, 2002; Xianming et al., 2002; Yuxia et al., 2002; Zehong et al., 2002; Chunjian et al., 2003; Haijie and Changshi, 2003; Jinghe, 2003; Linfeng, 2003; Yanhong et al., 2003; Junjiang et al., 2004; Shaohua, 2004; Sujuan and Haijun, 2004; Lifang and Guofeng, 2005; Shougang, 2005; Xiaoyan and Bainian, 2006; Zhi-Min et al., 2006; Chunyan, 2007; Dongsheng and Jimin, 2008; Qingfan and Hezhong, 2008; Tangheng, 2008; Rongxing and Linlin, 2009; Shugang et al., 2009; Weidong and Lihua, 2009; Yunhai, 2009; Changming, 2010; Cuixia and Cunji, 2010; Haiyan, 2010; Shiyao, 2010; Xiaojun, 2010; Yong, 2010; Jun et al., 2011; Leilei, 2011; Quanyou, 2011; Shaofeng and Xinfeng, 2011; Xiao-Mei, 2011; Yongchao et al., 2011; Haiqing, 2012; Jinbao et al., 2012; Tingguo et al., 2012; Xinnian and Lu, 2012; Jinliang and Yunyi, 2013; Wei et al., 2013; Yu, 2013; Zongsheng, 2013; Cailiang et al., 2014; Sujuan et al., 2014; Yanbo, 2014; Youjun, 2014; Xuexu et al., 2014; Hongying et al., 2015; Zhaomei and Lian, 2015; Zhijing et al., 2016; Hongying et al., 2016; Jianmin et al., 2016; Mao and Qiang, 2017; Zhixue et al., 2017; Wenhui and Shiliang, 2019; Wenhua et al., 2020; Fei, 2021; Laiqiang, 2021), involving 7,221 patients, met the inclusion criteria.

Flow chart of literature screening.

Flowchart depicting the study selection process. Identification: 867 records from database searches and 475 from other sources. Screening: 1,264 records screened, 78 duplicates removed, 1,167 records excluded. Eligibility: 97 full-text articles assessed, 32 excluded for various reasons. Inclusion: 65 studies included in qualitative synthesis and meta-analysis. 3.2 Basic characteristics of the included literature

After systematic screening and evaluation, a total of 7,221 patients were enrolled in this study, including 3,795 patients in the experimental group and 3,426 patients in the control group. All studies were RCTS.

The studies included patients with stable or unstable angina, with a mean age of 50–70 years in most studies. Of the 65 studies, 31 primarily focused on coronary heart disease (Wu et al., 2001; Jian and Xudong, 2002; Taojin, 2002; Yuxia et al., 2002; Zehong et al., 2002; Linfeng, 2003; Sujuan and Haijun, 2004; Xiaoyan and Bainian, 2006; Zhi-Min et al., 2006; Chunyan, 2007; Dongsheng and Jimin, 2008; Tangheng, 2008; Weidong and Lihua, 2009; Yunhai, 2009; Changming, 2010; Haiyan, 2010; Shiyao, 2010; Jun et al., 2011; Leilei, 2011; Xiao-Mei, 2011; Yongchao et al., 2011; Haiqing, 2012; Tingguo et al., 2012; Xinnian and Lu, 2012; Jinliang and Yunyi, 2013; Wei et al., 2013; Sujuan et al., 2014; Yanbo, 2014; Youjun, 2014; Hongying et al., 2016; Jianmin et al., 2016), 23 on unstable angina (Tong et al., 2001; Zhongtian and Rihui, 2001; Jing et al., 2002; Chunjian et al., 2003; Haijie and Changshi, 2003; Yanhong et al., 2003; Junjiang et al., 2004; Shaohua, 2004; Lifang and Guofeng, 2005; Shougang, 2005; Qingfan and Hezhong, 2008; Rongxing and Linlin, 2009; Shugang et al., 2009; Cuixia and Cunji, 2010; Xiaojun, 2010; Yong, 2010; Quanyou, 2011; Jinbao et al., 2012; Yu, 2013; Zongsheng, 2013; Hongying et al., 2015; Mao and Qiang, 2017; Wenhua et al., 2020), 9 on stable angina pectoris (Xianming et al., 2002; Jinghe, 2003; Shaofeng and Xinfeng, 2011; Cailiang et al., 2014; Xuexu et al., 2014; Zhaomei and Lian, 2015; Wenhui and Shiliang, 2019; Fei, 2021; Laiqiang, 2021) and 2 on general angina symptoms (Zhijing et al., 2016; Zhixue et al., 2017). The detailed basic characteristics of the included studies are shown in Table 2.

Evaluation table of literature quality.

Author Year Cases Male/Female Age (mean+SD) Variety of disease Outcome
T C
Xue fei 2021 T:30 C:30 17/13 16/14 T:65.21±4.42 C:65.21±4.46 Stable angina pectoris [1] [4] [5] [6]
Wang lai qiang 2021 T:50 C:50 27/23 25/25 T:63.47±5.89 C:62.56±6.57 Stable angina pectoris [1] [2] [4] [7]
Liang wen hua 2020 T:49 C:53 57/45 T+C:56.15±9.24 Unstable angina [1] [4] [5] [6] [7] [12]
Fan wen hui 2019 T:60 C:60 30/30 32/28 T:58.50±4.73 C:57.40 ±5.03 Stable angina pectoris [1] [2] [4] [14] [15] [16] [17]
Ye mao 2017 T:60 C:60 34/26 33/27 T:61.7±15.5 C:61.5±15.3 Unstable angina [1] [2] [12] [13] [14] [15] [16] [17] [5] [6]
Tian zhi xue 2017 T:40 C:40 28/12 27/13 T:60.3±5.4 C:60.8±5.7 Angina [1] [4] [5] [6] [7] [8]
Yao hong ying 2016 T:30 C:30 17/13 15/15 T:52.78±2.56 C:53.69±3.23 Coronary heart disease [1] [14] [15] [17]
Liin zhi jing 2016 T:150 C:150 79/71 76/74 T:65.2 C:64.1 Angina [1] [12] [13] [20]
Dai jian min 2016 T:37 C:36 Not mentioned Not mentioned Not mentioned Not mentioned Coronary heart disease [1] [2] [4] [14] [15] [16] [17]
Li hong ying 2015 T:52 C:54 31/21 33/21 Not mentioned Not mentioned Unstable angina [1] [2] [4]
Deng zhao mei 2015 T:30 C:30 35/25 T+C:57.7±5.91 Stable angina pectoris [1] [2]
Zhang you jun 2014 T:56 C:50 35/21 32/18 T:62 C:61 Coronary heart disease [1] [2] [3]
Yang su juan 2014 T:96 C:104 44/52 49/55 Not mentioned Not mentioned Coronary heart disease [1] [12] [13]
Su xue xu 2014 T:30 C:30 16/14 15/15 T:64.4±12.2 C:67.8±12.4 Stable angina pectoris [1] [2]
Peng cai liang 2014 T:40 C:40 Not mentioned Not mentioned Not mentioned Not mentioned Stable angina pectoris [1] [12] [13] [20]
Li yan bo 2014 T:50 C:50 28/22 24/26 T:64.5 C:66.5 Coronary heart disease [1]
Wu jin liang 2013 T:156 C:98 90/66 58/40 T:70 C:69.5 Coronary heart disease [1] [5] [6] [7] [8] [14] [15] [16]
Shang yu 2013 T:66 C:56 42/24 36/20 T:67±4.9 C:68±3.8 Unstable angina [1] [5] [6] [10] [11] [7]
Huang wei 2013 T:72 C:36 40/32 20/16 T:57±7 C:57±8 Coronary heart disease [1] [2]
Du zong sheng 2013 T:30 C:30 18/12 17/13 T:51.8±15.4 C:49.8 ±14.7 Unstable angina [1] [12] [13] [20] [23]
Yu hai qing 2012 T:103 C:48 68/35 32/16 T+C:59.2 Coronary heart disease [1] [2] [5] [6]
Shi jin bao 2012 T:35 C:32 20/15 18/14 T:58.1 C:60.2 Unstable angina [1] [2] [4]
Lu ting guo 2012 T:80 C:80 45/35 43/37 T:48.3 C:47.5 Coronary heart disease [1] [2] [12] [13]
Liu xin nian 2012 T:31 C:30 17/14 16/14 T:58.15±5.13 C:56.45±5.65 Coronary heart disease [20] [21] [22] [23]
Zhu lei lei 2011 T:23 C:23 15/8 14/9 T:58 ±3.23 C:56 ±3.29 Coronary heart disease [1] [2]
Zhang yong chao 2011 T:40 C:40 19/21 20/20 T:62.25±10.72 C:61.78±11.32 Coronary heart disease [2] [12]
Ma xiao mei 2011 T:60 C:60 36/24 38/22 T:58 C:59 Coronary heart disease [1] [2]
Li jun 2011 T:36 C:36 21/15 20/16 T:68±9 C:67±8 Coronary heart disease [1] [24] [25]
Gong quan you 2011 T:70 C:70 42/28 40/30 Not mentioned Not mentioned Unstable angina [1] [2]
Cai shao feng 2011 T:52 C:50 37/15 33/17 Not mentioned Not mentioned Stable angina pectoris [1] [2]
Lu shi yao 2010 T:43 C:42 28/15 24/18 T:62.6 C:64.1 Coronary heart disease [1]
Liu chang ming 2010 T:60 C:60 42/18 38/22 Not mentioned Not mentioned Coronary heart disease [1]
Liu cui xia 2010 T:40 C:38 28/12 29/9 T:57±8 C:56±9 Unstable angina [1]
Li xiao jun 2010 T:30 C:30 42/18 T+C:52±7 Unstable angina [1]
Jin yong 2010 T:62 C:50 40/22 36/14 T:80 C:79 Unstable angina [1] [2]
Huang hai yan 2010 T:42 C:40 22/20 21/19 T:58.2 C:56.2 Coronary heart disease [1] [2]
Yuan shu gang 2009 T:60 C:60 38/22 40/20 T:67.15 C:68.12 Unstable angina [1]
Ni wei dong 2009 T:36 C:32 42/26 T+C:52±7.5 Coronary heart disease [1]
Chen rong xing 2009 T:60 C:58 40/20 39/19 Not mentioned Not mentioned Unstable angina [2] [12] [13]
Cai yun hai 2009 T:69 C:66 35/34 31/35 T:46.39±10.17 C:45.12±8.97 Coronary heart disease [1]
Zhou tang heng 2008 T:48 C:42 30/18 29/13 T:64 C:61 Coronary heart disease [1] [2]
Zhang qing fan 2008 T:57 C:56 31/26 30/26 Not mentioned Not mentioned Unstable angina [1] [2]
Chen dong sheng 2008 T:60 C:40 44/16 30/10 T:56±1.56 C:56±1.53 Coronary heart disease [1] [2]
Yan chun yan 2007 T:60 C:60 81/39 Not mentioned Not mentioned Coronary heart disease [1] [23]
Zhang zhi min 2006 T:250 C:250 163/87 166/84 T:55.6±20.4 C:54.3±17.7 Coronary heart disease [14] [15] [16] [17]
Yang xiao yan 2006 T:40 C:40 24/16 23/17 T:55.7±4.3 C:54.9±4.9 Coronary heart disease [1] [24] [25]
Jiao shou gang 2005 T:50 C:42 28/22 24/18 T:58.6 C:56.7 Unstable angina [1] [2] [12] [14] [15] [17]
Chen li fang 2005 T:31 C:30 18/13 19/11 T:65.5 C:63.61 Unstable angina [1] [2]
Zhang shao hua 2004 T:21 C:18 17/4 15/3 T:68.7 C:68.1 Unstable angina [1] [20] [21] [22] [23]
Zhang jun jiang 2004 T:42 C:42 32/10 36/6 Not mentioned Not mentioned Unstable angina [1] [6] [10]
Yang su juan 2004 T:120 C:80 86/34 58/22 Not mentioned Not mentioned Coronary heart disease [1] [2]
Yu hai jie 2003 T:22 C:22 19/3 17/5 T:59.2 C:61.4 Unstable angina [1] [2]
Wang yan hong 2003 T:60 C:40 41/19 28/12 T:68.3±6.4 C:67.4±6.9 Unstable angina [1] [2] [5] [6] [8]
Shang jing he 2003 T:66 C:60 40/26 40/20 T:56.3 C:60.5 Stable angina pectoris [1] [2] [5] [6] [7] [14] [15] [16]
Niu chun jian 2003 T:30 C:30 16/14 15/15 T:60.7 C:61.4 Unstable angina [1] [12] [7] [14] [15] [10]
Liao lin feng 2003 T:40 C:25 27/13 14/11 T:62.43 C:61.56 Coronary heart disease [1] [2] [5] [6] [7] [8]
Zhao ze hong 2002 T:175 C:121 195/101 T+C:63.2±9.7 Coronary heart disease [1] [2] [12]
Zhao yu xia 2002 T:31 C:31 18/13 28/3 T:57±12 C:54±11 Coronary heart disease [14] [15] [16]
Xue jing 2002 T:29 C:29 16/13 15/14 T:61.2 C:60.5 Unstable angina [1] [2] [14] [15] [7] [19]
Li tao jin 2002 T:36 C:36 20/16 18/18 T:60.2±6.56 C:59.61±7.26 Coronary heart disease [1] [2] [4] [18]
Fu jian 2002 T:45 C:40 26/19 24/16 T:61±7.2 C:59±6.2 Coronary heart disease [1] [2] [3]
Fang xian ming 2002 T:30 C:30 23/7 24/6 T:56.8 C:57.2 Stable angina pectoris [1] [2] [3]
Xu zhong tian 2001 T:52 C:52 38/14 34/18 Not mentioned Not mentioned Unstable angina [1] [5] [6] [20] [9] [11]
Wang tong 2001 T:82 C:80 60/22 60/20 T+C:51.5±3.2 Unstable angina [1] [2] [5] [6] [10] [9]
Wang ling yun 2001 T:100 C:100 107/93 T+C:56.3 Coronary heart disease [1] [2]

T, experimental group, C, control group; A, Chinese patent medicine containing leech ingredients; B, conventional treatment; Efficacy evaluation indexes include; [1] Effective; [2] ECG efficacy; [3] Efficacy of main symptoms; [4] TCM symptom points; [5] Whole blood viscosity; [6] plasma viscosity (high + low); [7] Fibrinogen; [8] Hematocrit; [9] Sedimentation rate equation; [10] Platelet adhesion rate; [11] hematocrit; [12] frequency of angina attacks; [13] Duration of angina; [14] Total cholesterol; [15] Triglycerides; [16] High-density lipoprotein; [17] Low-density lipoprotein; [18] Blood glucose; [19] Prothrombin time; [20] ST-T changes; [21] Sum of ST changes; [22] systolic blood pressure; [23] heart rate; [24] Cardiac ejection fraction; [25] Left ventricular end-diastolic diameter.

 3.3 Quality evaluation of included studies

Among the 65 included studies, 56 studies were low-risk, 6 studies only mentioned randomization, but did not specify the random allocation method, rated as unclear risk, and 3 studies did not mention it. In terms of allocation concealment, 38 studies were rated as low risk, 6 studies did not give clear allocation as high risk, and the remaining 23 studies did not mention allocation concealment as unclear risk. In terms of research blinding, 25 studies mentioned it, 36 studies did not mention it, and 4 studies were rated as high risk because they could not be blinded due to different types of interventions included in the studies. In terms of completeness of outcome indicators, 17 items clearly stated that there was no loss of follow-up and were rated as low risk. Six items mentioned loss of follow-up, which was rated as high risk. The remaining 42 did not mention loss to follow-up and were rated as unclear risk. Data were reported selectively; 24 were low-risk and 41 were high-risk. Other risks of bias were only mentioned in 12 articles, and the rest were unclear. The risk of bias assessment of the included studies is shown in Figures 2, 3.

Proportion of items that generated risk of bias in the included literature.

Bar chart illustrating bias risks in research studies. Categories include random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other bias. Each bar displays proportions of low (green), unclear (yellow), and high (red) risk of bias. Most risks are primarily unclear, except random sequence generation and allocation concealment.

The proportion of items with bias risks in each literature work.

A risk of bias summary table for multiple studies is displayed. Each row represents a study identified by the author's name and year, and columns indicate different types of bias: random sequence generation, allocation concealment, blinding, incomplete outcome data, selective reporting, and other bias. Symbols are used to show bias risk: green circle with a plus for low risk, yellow circle with a question mark for unclear risk, and red circle with a minus for high risk. Most studies have mixed assessments, with variations in risks across categories. 3.4 Results 3.4.1 Total clinical effective rate

A total of 58 studies (Wu et al., 2001; Tong et al., 2001; Zhongtian and Rihui, 2001; Jian and Xudong, 2002; Jing et al., 2002; Taojin, 2002; Xianming et al., 2002; Zehong et al., 2002; Chunjian et al., 2003; Haijie and Changshi, 2003; Jinghe, 2003; Linfeng, 2003; Yanhong et al., 2003; Junjiang et al., 2004; Shaohua, 2004; Sujuan and Haijun, 2004; Lifang and Guofeng, 2005; Shougang, 2005; Xiaoyan and Bainian, 2006; Chunyan, 2007; Dongsheng and Jimin, 2008; Qingfan and Hezhong, 2008; Tangheng, 2008; Shugang et al., 2009; Weidong and Lihua, 2009; Changming, 2010; Cuixia and Cunji, 2010; Haiyan, 2010; Shiyao, 2010; Xiaojun, 2010; Yong, 2010; Jun et al., 2011; Leilei, 2011; Quanyou, 2011; Shaofeng and Xinfeng, 2011; Xiao-Mei, 2011; Haiqing, 2012; Jinbao et al., 2012; Tingguo et al., 2012; Jinliang and Yunyi, 2013; Wei et al., 2013; Yu, 2013; Zongsheng, 2013; Cailiang et al., 2014; Yanbo, 2014; Youjun, 2014; Xuexu et al., 2014; Hongying et al., 2015; Zhaomei and Lian, 2015; Zhijing et al., 2016; Hongying et al., 2016; Jianmin et al., 2016; Mao and Qiang, 2017; Zhixue et al., 2017; Wenhui and Shiliang, 2019; Wenhua et al., 2020; Fei, 2021; Laiqiang, 2021) with total clinical response rate as the outcome index, a total of 6,065 patients were included. The total response rate of 58 studies was homogeneous (P = 0.68, I2 = 0%), and a fixed effect model was set. Meta-analysis results showed that: The total effective rate of the treatment group was higher than that of the control group, and the difference was statistically significant [OR = 3.70, 95%CI (3.19, 4.31), Z = 17.05, P < 0.00001], indicating that in terms of improving the total effective rate of coronary heart disease, the combination of conventional western medicine with leech Chinese patent medicine was significantly better than the simple conventional western medicine (Figure 4).

Total effective rate.

Forest plot illustrating a meta-analysis of various studies comparing experimental and control groups. It lists study names, events, totals, weights, odds ratios, and confidence intervals. An overall odds ratio of 3.70 with a 95% confidence interval of 3.19 to 4.31 is shown, favoring the experimental group. The diamond shape at the bottom represents the overall effect size. Heterogeneity statistics include Chi-square equals 51.47, degrees of freedom equals 57, and I-squared equals 0%. 3.4.2 ECG efficacy

Thirty eight studies (Wu et al., 2001; Tong et al., 2001; Jian and Xudong, 2002; Jing et al., 2002; Taojin, 2002; Xianming et al., 2002; Zehong et al., 2002; Haijie and Changshi, 2003; Jinghe, 2003; Linfeng, 2003; Sujuan and Haijun, 2004; Lifang and Guofeng, 2005; Shougang, 2005; Dongsheng and Jimin, 2008; Qingfan and Hezhong, 2008; Tangheng, 2008; Rongxing and Linlin, 2009; Yunhai, 2009; Haiyan, 2010; Yong, 2010; Leilei, 2011; Quanyou, 2011; Shaofeng and Xinfeng, 2011; Xiao-Mei, 2011; Yongchao et al., 2011; Haiqing, 2012; Jinbao et al., 2012; Tingguo et al., 2012; Wei et al., 2013; Sujuan et al., 2014; Youjun, 2014; Xuexu et al., 2014; Hongying et al., 2015; Zhaomei and Lian, 2015; Jianmin et al., 2016; Mao and Qiang, 2017; Wenhui and Shiliang, 2019; Laiqiang, 2021) (n = 4,190) reported the ECG efficacy after treatment. The results of meta-analysis under fixed effects model (I2 = 2%, P < 0.0001) showed that the group containing leech Chinese medicine combined with conventional treatment had better ECG efficacy after treatment, and the difference was statistically significant [OR = 2.58, 95%CI (2.23, 2.99), P < 0.0001] (Figure 5).

Comparison of ECG efficacy between leech combined with conventional treatment and conventional treatment alone.

Forest plot showing a meta-analysis of multiple studies. It lists study names, experimental and control events, total participants, weight, and odds ratios with confidence intervals. Horizontal lines represent confidence intervals, and dots indicate odds ratios. The summary result at the bottom shows an overall odds ratio of 2.58, favoring experimental interventions over control. 3.4.3 TCM symptoms and efficacy

Three studies (Jinbao et al., 2012; Hongying et al., 2015; Wenhui and Shiliang, 2019) (n = 293) reported the efficacy of TCM symptoms after treatment, and the difference between the two groups was statistically significant [OR = 3.75, 95%CI (1.81, 7.73), Z = 3.57, P = 0.0004]. The Chinese patent medicine containing leech combined with conventional medicine in the treatment of CHD could improve the efficacy of TCM symptoms than conventional western medicine alone (Figure 6).

Comparison of the efficacy of leech combined with conventional treatment and conventional treatment alone for TCM symptoms.

Forest plot displaying odds ratios for three studies comparing experimental and control groups. Odds ratios for individual studies: Fanwenhui 2019 (3.67), Lihongying 2015 (3.43), Shijinbao 2012 (4.62). The overall odds ratio is 3.75, with a 95% confidence interval of 1.81 to 7.73. The heterogeneity statistic shows Chi-squared equals 0.08, and the test for overall effect shows a Z score of 3.57 and P-value of 0.0004. A diamond represents the pooled odds ratio. 3.4.4 Frequency of angina pectoris

Nine studies (Shougang, 2005; Rongxing and Linlin, 2009; Yongchao et al., 2011; Tingguo et al., 2012; Zongsheng, 2013; Cailiang et al., 2014; Zhijing et al., 2016; Mao and Qiang, 2017; Wenhua et al., 2020) (n = 1,112) reported the frequency of angina pectoris in each group after treatment. The results of Meta-analysis showed that the frequency of angina pectoris attack after treatment with leech Chinese medicine combined with conventional medication was lower than that of conventional treatment alone, and the incidence of angina pectoris was significantly reduced. The difference between the two groups was statistically significant [SMD = −1.13, 95%CI (-1.52, −0.75), Z = 5.75, P ≤ 0.00001] (Figure 7).

Comparison of frequency of angina episodes between leech combined with conventional treatment and conventional treatment alone.

Forest plot showing a meta-analysis of studies comparing experimental and control groups. Each study is listed with mean, standard deviation, and weight percentage. The plot includes standard mean differences with 95% confidence intervals. The overall effect size is -1.13 with a confidence interval of [-1.52, -0.75]. The heterogeneity measures are tau squared equals 0.30, chi squared equals 67.18, degrees of freedom equals 8, p-value less than 0.00001, and I squared equals 88%. The overall effect test is significant with Z equals 5.75 and p less than 0.00001. 3.4.5 Whole blood viscosity

Twelve studies (Tong et al., 2001; Zhongtian and Rihui, 2001; Jinghe, 2003; Linfeng, 2003; Yanhong et al., 2003; Haiqing, 2012; Jinliang and Yunyi, 2013; Yu, 2013; Mao and Qiang, 2017; Zhixue et al., 2017; Wenhua et al., 2020; Fei, 2021) (n = 1,446) reported on post-treatment whole blood viscosity levels in each group. Meta-analysis results showed that: The whole blood viscosity level was lower after the treatment of Chinese patent medicine containing leech ingredients combined with conventional medication than that of conventional treatment alone, and the difference between the two groups was statistically significant [SMD = −1.35, 95%CI (−2.10, −0.60), Z = 3.53, P = 0.0004] (Figure 8).

Comparison of whole blood viscosity between leech combined with conventional treatment and conventional treatment alone.

Forest plot showing a meta-analysis of studies comparing experimental and control groups. Studies are listed with mean, standard deviation, and total for each group. Standardized mean differences and confidence intervals are displayed with green squares and lines. The overall effect size is marked with a diamond at -1.35, favoring the experimental group. Heterogeneity statistics are provided below. 3.4.6 Plasma viscosity

Blood urea nitrogen levels 12 studies (Tong et al., 2001; Zhongtian and Rihui, 2001; Jinghe, 2003; Linfeng, 2003; Yanhong et al., 2003; Haiqing, 2012; Jinliang and Yunyi, 2013; Yu, 2013; Mao and Qiang, 2017; Zhixue et al., 2017; Wenhua et al., 2020; Fei, 2021) (n = 1,446) reported changes in plasma viscosity after treatment in each group. Meta-analysis results showed that: The plasma viscosity level after treatment with leech Chinese proprietary medicine combined with conventional medication was lower than that of conventional treatment alone, and the difference was statistically significant [SMD = −0.81, 95%CI(-1.24, −0.37), Z = 3.66, P = 0.0003] (Figure 9).

Comparison of plasma viscosity between leech combined with conventional treatment and conventional treatment alone.

Forest plot depicting a meta-analysis of studies comparing experimental and control groups. Each line represents a study with a green square, showing the standardized mean difference and the confidence interval. The diamond at the bottom indicates the overall effect size of negative point eight one, with a confidence interval from negative one point two four to negative zero point three seven, favoring the experimental group. Heterogeneity statistics and other methodological details are also included. 3.4.7 Fibrinogen

Eight studies (Chunjian et al., 2003; Jinghe, 2003; Linfeng, 2003; Jinliang and Yunyi, 2013; Yu, 2013; Zhixue et al., 2017; Wenhua et al., 2020; Laiqiang, 2021) (n = 909) reported fibrinogen levels in each group after treatment. Meta-analysis results showed that: The level of fibrinogen in the treatment group was lower than that in the control group [SMD = −0.99, 95%CI (−1.52, −0.47), Z = 3.69, P = 0.0002] (Figure 10).

Comparison of leech combined with conventional treatment and conventional treatment alone for fibrinogen.

Forest plot showing the standard mean differences with 95% confidence intervals for various studies. The plot includes studies by liangwenhua 2020 through wujinliang 2013. The overall effect size is -0.99 with a heterogeneity of 92%. The plot favors the control group. The diamond represents the pooled estimate. 3.4.8 Total cholesterol

Fifteen studies (Jing et al., 2002; Taojin, 2002; Yuxia et al., 2002; Chunjian et al., 2003; Jinghe, 2003; Lifang and Guofeng, 2005; Shougang, 2005; Zhi-Min et al., 2006; Xiao-Mei, 2011; Yongchao et al., 2011; Jinliang and Yunyi, 2013; Hongying et al., 2016; Jianmin et al., 2016; Mao and Qiang, 2017; Wenhui and Shiliang, 2019) (n = 1858) reported the serum total cholesterol levels of each group after treatment. The results of Meta-analysis showed that the serum total cholesterol level after treatment with leech Chinese medicine combined with conventional treatment was lower than that of conventional treatment alone. The difference between the two groups was statistically significant [SMD = −1.55, 95%CI (−2.11, −0.99), Z = 5.41, P ≤ 0.00001] (Figure 11).

Comparison of total cholesterol between leech combined with conventional treatment and conventional treatment alone.

Forest plot showing a meta-analysis of studies comparing experimental and control groups. Each study is listed with mean, standard deviation, total participants, and weight percentage. Green squares with horizontal lines represent the standard mean difference and ninety-five percent confidence intervals. A diamond at the bottom represents the overall effect size, favored towards the experimental group with a value of -1.55. Heterogeneity is indicated with Tau-squared equals 1.15, Chi-squared equals 388.07, degrees of freedom equals 14, and I-squared equals 96 percent. The test for overall effect is significant with a Z-score of 5.41. 3.4.9 Triglycerides

Fifteen studies (Jing et al., 2002; Taojin, 2002; Yuxia et al., 2002; Chunjian et al., 2003; Jinghe, 2003; Lifang and Guofeng, 2005; Shougang, 2005; Zhi-Min et al., 2006; Xiao-Mei, 2011; Yongchao et al., 2011; Jinliang and Yunyi, 2013; Hongying et al., 2016; Jianmin et al., 2016; Mao and Qiang, 2017; Wenhui and Shiliang, 2019) (n = 1858) reported the serum triglyceride levels of each group after treatment. The results of Meta-analysis showed that the serum triglyceride level of the treatment with leech Chinese medicine combined with conventional treatment was lower than that of conventional treatment alone. The difference between the two groups was statistically significant [SMD = −1.12, 95%CI (−1.55, −0.69), Z = 5.10, P ≤ 0.00001] (Figure 12).

Comparison of leeches combined with conventional treatment and conventional treatment alone triglyceride.

Forest plot showing standardized mean differences between experimental and control groups across multiple studies. Each study is listed with corresponding means, standard deviations, and weights. Confidence intervals for individual and overall effects are displayed with horizontal lines. The total effect size is marked by a diamond, indicating a mean difference of -1.12, favoring the experimental group. Heterogeneity statistics indicate significant variability (Tau² = 0.66; I² = 94%). 3.4.10 High density lipoprotein

Eleven studies (Taojin, 2002; Yuxia et al., 2002; Jinghe, 2003; Lifang and Guofeng, 2005; Shougang, 2005; Zhi-Min et al., 2006; Xiao-Mei, 2011; Jinliang and Yunyi, 2013; Jianmin et al., 2016; Mao and Qiang, 2017; Wenhui and Shiliang, 2019) (n = 1,600) reported changes in HDL after treatment in each group. Meta-analysis results showed that: The level of high-density lipoprotein after leech combined with conventional medication was higher than that of conventional treatment alone, but there was no statistical significance [SMD = 0.37, 95%CI (0.05, 0.69), Z = 2.25, P = 0.02] (Figure 13).

Comparison of leech combined with conventional treatment and conventional treatment alone for HDL.

Forest plot showing a meta-analysis of eleven studies comparing experimental and control groups. Each study lists mean differences and confidence intervals. The combined effect size shows a standardized mean difference of 0.37 with a confidence interval of 0.05 to 0.69, indicating a statistically significant overall effect in favor of the experimental group. Heterogeneity is high with an I-squared of 89 percent. 3.4.11 Low density lipoprotein

Nine studies (Taojin, 2002; Lifang and Guofeng, 2005; Shougang, 2005; Zhi-Min et al., 2006; Xiao-Mei, 2011; Hongying et al., 2016; Jianmin et al., 2016; Mao and Qiang, 2017; Wenhui and Shiliang, 2019) (n = 1,218) reported the levels of low-density lipoprotein in each group after treatment. The results of Meta-analysis showed that the level of low-density lipoprotein after treatment with leech Chinese medicine combined with conventional treatment was lower than that of conventional treatment alone. The difference between the two groups was statistically significant [SMD = −0.75, 95%CI (−1.29, −0.21), Z = 2.74, P < 0.006] (Figure 14).

Leech combined with conventional treatment compared with conventional treatment alone for LDL.

Forest plot showing the standardized mean differences between experimental and control groups across nine studies. Each study is represented by a square and horizontal line indicating effect size and confidence interval, respectively. The overall effect is denoted by a diamond at -0.75, with a 95% confidence interval ranging from -1.29 to -0.21. Heterogeneity statistics are provided, with a chi-squared value of 139.91, a degrees of freedom of eight, and an I-squared of 94%. 3.4.12 Adverse reactions

Twenty six studies (Wu et al., 2001; Jian and Xudong, 2002; Taojin, 2002; Xianming et al., 2002; Haijie and Changshi, 2003; Junjiang et al., 2004; Shaohua, 2004; Lifang and Guofeng, 2005; Shougang, 2005; Xiaoyan and Bainian, 2006; Dongsheng and Jimin, 2008; Qingfan and Hezhong, 2008; Rongxing and Linlin, 2009; Shugang et al., 2009; Weidong and Lihua, 2009; Jun et al., 2011; Shaofeng and Xinfeng, 2011; Xiao-Mei, 2011; Jinbao et al., 2012; Wei et al., 2013; Yu, 2013; Hongying et al., 2015; Hongying et al., 2016; Jianmin et al., 2016; Mao and Qiang, 2017; Wenhui and Shiliang, 2019) (n = 2,406) reported the adverse reactions that occurred in the patients of each group after treatment. The number of adverse reactions and their symptoms are presented in Table 3. All adverse reactions were mild and resolved spontaneously after treatment. All adverse reactions were effectively managed through regular monitoring and appropriate intervention. The study found that compared with the group that only received conventional treatment, the incidence of adverse events in the group that received combined treatment with herbal medicine from earthworms did not significantly increase. The results of the meta-analysis showed that there was no statistically significant difference in the incidence of adverse reactions between the two groups [RD = 0.00, 95%CI (−0.01, 0.01), P = 0.90] (Figure 15).

Adverse reaction symptom.

Adverse reaction
Author Year Number Symptoms
Yao hong ying 2016 1 Mild vomiting
Li hong ying 2015 1 Mild thirst
Ma xiao mei 2011 3 Slight headache
Liu cui xia 2010 2 Minor bleeding on the skin
Yuan shu gang 2009 1 Slight headache
Chen rong xing 2009 1 Gastric discomfort, relieved by eating
Yang xiao yan 2006 1 Gastric discomfort, relieved by eating
Fu jian 2002 3 Gastric discomfort, relieved by eating
Wang ling yun 2001 1 Gastrointestinal discomfort

Adverse reactions.

Forest plot showing the risk difference with 95% confidence intervals for multiple studies. Each line represents a study, with a point estimate and horizontal line indicating the confidence interval. All studies except one favor neither the experimental nor control group significantly. The overall risk difference is -0.00 with a confidence interval of [-0.01, 0.01]. Total events are 1 for experimental and 9 for control. Heterogeneity statistics show no significant variation between studies. 3.5 Subgroup analysis

Subgroup analyses were performed on specific outcomes based on two primary intervention factors: drug type and treatment duration. The results consistently demonstrated that the experimental treatment outperformed the control group. The overall pooled odds ratio for all treatment combinations across subgroups classified by drug type was 3.76 (95% CI: 3.08–4.60), indicating a robust and consistent effect of the experimental treatment across all subgroups. Similarly, the overall effect across all treatment durations in the subgroups stratified by treatment duration was 3.51 (95% CI: 3.02–4.08), suggesting that treatment duration did not significantly impact the results, with the experimental treatment remaining effective across various timeframes. Statistical significance was observed in all subgroups. The forest plots of the results are presented in Figures 16, 17.

Drug classification grouping.

Forest plot illustrating multiple studies comparing various treatments with control groups. The treatments include Leeches Capsules, Tongxinluo Capsules, Shuxuetong Injection, Blood Circulation Capsules, Leeches Three Yellows Decoction, Ginseng and Leeches Pills, Pulse Blood Health Capsules, and Astragalus Leeches Notoginseng Decoction. Each study displays odds ratios with 95% confidence intervals. Diamonds represent combined estimates, with statistical values highlighting heterogeneity and overall effects. The x-axis represents the odds ratio on a logarithmic scale, indicating whether results favor experimental or control groups.

Treatment time grouping.

Forest plot showing odds ratios of various studies comparing experimental and control groups. The studies are grouped into subcategories based on time periods: less than or equal to two weeks, greater than two weeks to less than or equal to four weeks, and greater than four weeks to less than or equal to eight weeks. Odds ratios with confidence intervals and weights are listed. Diamonds represent pooled estimates for each subgroup and overall effect, indicating an overall favor towards the experimental group. Heterogeneity statistics are provided for each group. 3.6 Publication bias analysis

The risk of publication bias was evaluated using funnel plots for the total effective rate and ECG efficacy of the primary outcome indicators, as shown in Figures 18, 19, respectively. It was observed that the scatter points of the funnel plot of the two outcome indicators were distributed above the horizontal axis, but the distribution was basically symmetrical, suggesting that there was no risk of publication bias.

Funnel plot of total clinical response rate.

Funnel plot displaying effect size as log odds ratio on the x-axis and standard error on the y-axis. Points are mostly clustered symmetrically within the funnel-shaped dashed lines, indicating low publication bias.

Funnel plot of ECG efficacy.

Funnel plot with log-transformed odds ratios on the x-axis and standard errors on the y-axis. Data points are dispersed within a triangular region formed by dashed blue lines, indicating variability in study results. 3.7 GRADE assessment

Using the GRADE approach, we conducted a certainty assessment for the primary outcome measures. For effective and ECG efficacy, the evidence was downgraded by one level due to serious concerns about risk of bias, resulting in moderate certainty of evidence (Table 4). For traditional Chinese medicine symptom efficacy, the evidence was rated as moderate certainty due to a high risk of bias. For the frequency of angina pectoris, the evidence was downgraded by two levels due to both a high risk of bias and publication bias, leading to low-certainty evidence (Table 5). For whole blood viscosity, plasma viscosity, and fibrinogen, some studies had limitations in clinical applicability, high uncertainty in results, and uncontrolled confounding factors, resulting in low-certainty evidence (Table 6). Regarding the biochemical indicator total cholesterol, although there were significant inconsistencies and precision issues, the risk of bias was low, and the evidence was rated as moderate certainty. For triglycerides, considering the substantial inconsistencies, precision issues, and the potential impact of residual confounding factors, the evidence was downgraded by two levels, ultimately rated as low certainty. For high-density lipoprotein (HDL), despite some inconsistencies and precision issues, the risk of bias was low, and the evidence was rated as moderate certainty. For low-density lipoprotein (LDL), due to severe inconsistencies, precision issues, and substantial publication bias, the evidence was downgraded by two levels, resulting in very low-certainty evidence (Table 7).

Effective and ECG efficacy assessment.

Certainty assessment No. of patients Effect Certainty Importance
No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations New comparison Placebo Relative (95% CI) Absolute (95% CI)
Effective
58 Randomised trials Serious Not serious Not serious Not serious None 2922/3218 (90.8%) 2096/2847 (73.6%) OR 3.70 (3.19 to 4.31) 175 more per 1,000 (from 163 more to 187 more) ⨁⨁⨁○ Moderate CRITICAL
Electrocardiogram efficacy
38 Randomised trials Serious Not serious Not serious Not serious None 1795/2230 (80.5%) 1224/1960 (62.4%) OR 2.58 (2.23 to 2.99) 186 more per 1,000 (from 163 more to 208 more) ⨁⨁⨁○ Moderate CRITICAL

CI, confidence interval; MD, mean difference; OR, odds ratio.

TCM symptoms and frequency of angina pectoris.

Certainty assessment No. of patients Effect Certainty Importance
No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations New comparison Placebo Relative (95% CI) Absolute (95% CI)
Traditional Chinese medicine, Symptom, Efficacy (二)
3 Randomised trials Serious Not serious Not serious Not serious None 136/147 (92.5%) 112/146 (76.7%) OR 3.75 (1.81 to 7.73) 158 more per 1,000 (from 89 more to 195 more) ⨁⨁⨁○ Moderate IMPORTANT
Frequency of angina pectoris
9 Randomised trials Serious Very serious Not serious Not serious All plausible residual confounding would reduce the demonstrated effect 559 553 - MD 1.14 lower (1.25 lower to 1.04 lower) ⨁⨁○○ Low IMPORTANT

CI, confidence interval; MD, mean difference; OR, odds ratio

Whole blood viscosity, plasma viscosity, and fibrinogen.

Certainty assessment No. of patients Effect Certainty Importance
No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations New comparison Placebo Relative (95% CI) Absolute (95% CI)
Whole blood viscosity
12 Randomised trials Not serious Serious Serious Serious All plausible residual confounding would reduce the demonstrated effect 804 642 - MD 0.69 lower (0.73 lower to 0.64 lower) ⨁⨁○○ Low IMPORTANT
Plasma viscosity
12 Randomised trials Not serious Serious Not serious Serious None 804 642 - MD 0.19 lower (0.22 lower to 0.17 lower) ⨁⨁○○ Low IMPORTANT
Fibrinogen
8 Randomised trials Not serious Serious Not serious Serious None 497 412 - MD 0.63 lower (0.7 lower to 0.55 lower) ⨁⨁○○ Low IMPORTANT

CI, confidence interval; MD, mean difference; OR, odds ratio.

Total cholesterol triglycerides HDL and LDL.

Certainty assessment No. of patients Effect Certainty Importance
No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations New comparison Placebo Relative (95% CI) Absolute (95% CI)
Total cholesterol
15 Randomised trials Not serious Serious Not serious Serious All plausible residual confounding would reduce the demonstrated effect 966 892 - MD 0.79 lower (0.84 lower to 0.75 lower) ⨁⨁⨁○ Moderate IMPORTANT
Triglycerides
15 randomised trials not serious very serious not serious serious all plausible residual confounding would reduce the demonstrated effect 966 892 - MD 0.62 lower (0.67 lower to 0.58 lower) ⨁⨁○○ Low IMPORTANT
High density lipoprotein
11 Randomised trials Not serious Serious Serious Not serious All plausible residual confounding would reduce the demonstrated effect 837 763 - MD 0.11 higher (0.09 higher to 0.14 higher) ⨁⨁⨁○ Moderate IMPORTANT
Low density lipoprotein
9 Randomised trials Not serious Very serious Not serious Serious Publication bias strongly suspected all plausible residual confounding would reduce the demonstrated effect 614 604 - MD 0.63 lower (0.71 lower to 0.54 lower) ⨁○○○ Very low IMPORTANT
4 Discussion

According to the results of this meta-analysis, Chinese patent medicine containing leech has shown clinical efficacy in the treatment of coronary heart disease, especially in improving the overall cure rate, abnormal electrocardiogram, hemorheology indexes and TCM symptom scores. The treatment group was superior to conventional western medicine in reducing the frequency of angina pectoris, improving the ischemic changes of electrocardiogram and regulating blood lipid levels. This may elucidate the effective effects of leech components on relieving angina pectoris and improving myocardial ischemia can be clarified.

The results of this meta-analysis show that leech-based treatments significantly improved the total effective rate and ECG outcomes in CHD patients. Specifically, the treatment group exhibited better clinical responses compared to those receiving only conventional treatments. This is crucial, as CHD patients typically suffer from ischemic changes reflected in abnormal ECG results (Albus et al., 2017; Su et al., 2023). The improvement in ECG outcomes suggests that hirudin play a role in mitigating myocardial ischemia. Hirudin, by inhibiting thrombin, directly reduces thrombosis and platelet aggregation, thereby enhancing coronary blood flow (Junren et al., 2021). This improvement likely contributes to the observed reduction in ischemic changes on the ECG.

Another critical finding is the significant reduction in the frequency of angina pectoris attacks in the treatment group, alongside improvements in hemorheological parameters whole blood and plasma viscosity. These results suggest that leech-based treatments contribute to better blood flow, particularly in coronary microcirculation. The reduction in blood viscosity, facilitated by hirudin’s anticoagulant properties, enhances tissue perfusion, ensuring that oxygen and nutrients reach ischemic myocardial tissue more efficiently. This is consistent with the known mechanisms of hirudin, which improves blood fluidity and prevents clot formation (Junren et al., 2021; Qiu et al., 2022), thus reducing the incidence of angina attacks and alleviating myocardial ischemia.

The meta-analysis also demonstrated significant improvements in lipid profiles, including reductions in total cholesterol, LDL, and triglycerides, along with a modest increase in HDL. These lipid changes are important for the long-term management of CHD, as they help slow the progression of atherosclerosis (Kamstrup, 2021; Shaya et al., 2022; Alloubani et al., 2021; Humm et al., 2023; Ueki et al., 2024) By improving lipid metabolism, substances in leeches may help stabilize atherosclerotic plaques, reducing the risk of plaque rupture and subsequent cardiovascular events. The observed lipid improvements may be attributed to the anti-inflammatory effects of leech components, which can reduce lipid oxidation and promote healthier vascular function.

The clinical benefits observed in this study are closely tied to the pharmacological properties ofsubstances in leeches. Hirudin, as a potent anticoagulant, plays a central role in preventing thrombus formation and improving blood flow (Junren et al., 2021). Its ability to reduce fibrinogen levels and enhance blood fluidity is crucial in alleviating myocardial ischemia. Moreover, the reduction in blood viscosity enhances coronary microcirculation, leading to better tissue perfusion and a reduction in ischemic damage to the heart (Del Buono et al., 2021).

Additionally, the improvement in lipid metabolism, evidenced by the decrease in LDL and increase in HDL, is likely due to the anti-inflammatory and antioxidant properties of leech components (Junren et al., 2021). These effects help reduce oxidative stress and inflammation, which are key factors in the progression of atherosclerosis (Kong et al., 2022; Attiq et al., 2024; Violi et al., 2024; Guo et al., 2024). Moreover, leech components’ ability to promote nitric oxide (NO) release by up-regulating endothelial nitric oxide synthase (eNOS) enhances vascular relaxation, improves coronary perfusion, and contributes to better endothelial function, all of which are essential for managing CHD (Junren et al., 2021; Jaishankar et al., 2023; Sun et al., 2025).

 5 Limitation

This study has several limitations. Firstly, the quality of some of the included studies was relatively low, particularly regarding randomization, allocation concealment, and blinding, where descriptions were unclear, potentially compromising the reliability of the results. Secondly, some studies had small sample sizes and short follow-up durations, making it difficult to assess the long-term efficacy and safety of the treatment comprehensively. Additionally, there was heterogeneity in the treatment protocols and traditional Chinese medicine formulas used, which could contribute to variations in the results and limit the ability to assess the efficacy of individual treatment plans clearly. Moreover, most of the studies included in this analysis were conducted in China, with the majority of the literature being in Chinese, which may introduce regional and cultural biases, thereby limiting the generalizability of the findings. Despite conducting a thorough literature search, there is still the possibility of publication bias, particularly with respect to the underreporting of negative results. Finally, the existing studies do not provide an in-depth exploration of the specific mechanisms of action of the leech-derived components, the mechanism by which hirudin exerts its effects through improving endothelial function, nitric oxide production, and regulating inflammatory responses is primarily based on existing pharmacological research and theoretical speculation, rather than being directly supported by the clinical data from this study, preventing a full understanding of their precise role in treating coronary heart disease. Special attention must be given to the potential interaction between bioactive components extracted from leeches and conventional anticoagulant or cardiovascular medications. While the therapeutic benefits of leech extracts are evident, combining these extracts with other medications requires careful monitoring of bleeding risks in patients. Some patients may have a history of prior medications or multiple comorbidities, which could influence treatment outcomes. Due to the design and scope of the current study, these factors were not fully accounted for. Although we evaluated several alternative biomarkers in this study, which provide valuable insights into biological effects, it is important to emphasize that these biomarkers cannot directly demonstrate clinical benefit. While they may reflect underlying biological mechanisms or the impact of therapeutic interventions, they are not equivalent to clinical endpoints, such as myocardial infarction, mortality, or quality of life, which are the critical measures for determining the clinical significance of a treatment. Therefore, although alternative biomarkers can serve as useful early predictors, they cannot fully substitute for definitive clinical outcomes. Future research should focus on further exploring these mechanisms, prioritizing clinical endpoints, validating the relationship between alternative biomarkers and actual clinical benefits, and assessing treatment efficacy across diverse patient populations and coronary artery disease subtypes to provide more precise clinical guidance.

 6 Conclusion

The results of this meta-analysis show that the Chinese patent medicine containing leech has good clinical efficacy in the treatment of coronary heart disease, which can significantly improve the symptoms, electrocardiogram performance and hemorheological indicators of patients, and has high safety. Its multi-target and synergistic mechanism provide a potentially effective TCM treatment for CHD.

Although this study has a certain clinical guiding significance, due to the low quality of some included studies, more high-quality, large sample and long-term follow-up randomized controlled trials are still needed to further verify its efficacy and safety, and clarify its mechanism of action, optimal treatment regimen and applicable population. In general, the potential of Chinese patent medicine containing leech in the comprehensive treatment of coronary heart disease is worthy of further research and application.

 Data availability statement

The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.

 Author contributions

ZZ: Data curation, Software, Writing – original draft, Writing – review and editing, Formal Analysis. DY: Investigation, Writing – review and editing, Formal Analysis, Data curation, Writing – original draft. ML: Validation, Writing – review and editing, Data curation, Investigation. YJ: Investigation, Writing – review and editing, Formal Analysis. JZ: Supervision, Funding acquisition, Resources, Writing – review and editing.

 Funding

The author(s) declare that financial support was received for the research and/or publication of this article. This work was funded by the National Natural Science Foundation of China (grant number 82160875), District Natural Science Research Fund (2022JJD140107), Zheng Jinghui - Academic Affairs Office - Fifth Batch of National Outstanding Traditional Chinese Medicine Clinical Talent Cultivation Program (grant number 06F24006) and Guangxi First-Class Discipline Construction Project (Gui Jiao Ke Yan [2022] No. 1).

Thanks to all authors for their valuable contributions to this manuscript.

 Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

 Generative AI statement

The author(s) declare that no Generative AI was used in the creation of this manuscript.

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 Supplementary material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fphar.2025.1643611/full#supplementary-material

Abbreviations

CHD, Coronary heart disease; CNKI, China National Knowledge Infrastructure; VIP, VIP China Science and Technology Journal Database; RCTs, Randomized controlled trials; SMD, Standardized Mean Difference; CI, Confidence intervals; OR, Odds Ratio; TCM, Traditional Chinese medicine; RD, Relative risk difference; MD, Mean difference.

 References Albus C. Barkhausen J. Fleck E. Haasenritter J. Lindner O. Silber S. (2017). The diagnosis of chronic coronary heart disease. Dtsch. Arzteblatt Int. 114 (42), 712–719. 10.3238/arztebl.2017.0712 29122104 Alloubani A. Nimer R. Samara R. (2021). Relationship between hyperlipidemia, cardiovascular disease and stroke: a Systematic Review. Curr. Cardiol. Rev. 17 (6), e051121189015. 10.2174/1573403x16999201210200342 33305711 Attiq A. Afzal S. Ahmad W. Kandeel M. (2024). Hegemony of inflammation in atherosclerosis and coronary artery disease. Eur. J. Pharmacol. 966, 176338. 10.1016/j.ejphar.2024.176338 38242225 Cailiang P. Songshan G. Ning J. (2014). Clinical observation on the treatment of stable angina pectoris with astragalus capsule. Heilongjiang J. Traditional Chin. Med. 43 (5), 19–20. Changming L. (2010). 120 cases of coronary heart disease treated with leech and sanhuang tang. Guangming J. Chin. Med. 25 (09), 1625–1626. 10.3969/j.issn.1003-8914.2010.09.045 Chunjian N. Xiaobing W. Tianyu G. (2003). Clinical observation on the treatment of unstable angina pectoris with blood-sparing injection solution. Nei Mongol J. Traditional Chin. Med. (S1), 4. 10.16040/j.cnki.cn15-1101.2003.s1.003 Chunmiao Y. Yuan L. Yongqing Z. Qiu J. Lingna W. (2024). Herbal textual research on hirudo. Chin. J. Mod. Appl. Pharm. 41 (19), 2648–2657. 10.13748/j.cnki.issn1007-7693.20230875 Chunyan Y. (2007). Clinical observation of Tongxinluo in the treatment of angina pectoris of coronary heart disease. Pract. J. Cardiac Cereb. Pneumal Vasc. Dis. 15 (3), 217–218. 10.3969/j.issn.1008-5971.2007.03.020 Cuixia L. Cunji F. (2010). Therapeutic efficacy of leech and blood stasis-expelling soup in the treatment of unstable angina pectoris. China Pract. Med. 5 (05), 137–138. 10.14163/j.cnki.11-5547/r.2010.05.019 Del Buono M. G. Montone R. A. Camilli M. Carbone S. Narula J. Lavie C. J. (2021). Coronary microvascular dysfunction across the spectrum of cardiovascular diseases: JACC State-of-the-Art Review. J. Am. Coll. Cardiol. 78 (13), 1352–1371. 10.1016/j.jacc.2021.07.042 34556322 Dongsheng C. Jimin M. (2008). Clinical observation on the treatment of angina pectoris in coronary heart disease by Long Hirudan. Hubei J. Traditional Chin. Med. 30 (11), 27–28. 10.3969/j.issn.1000-0704.2008.11.015 Fei X. (2021). Effect of Qizhi Sanqi Decoction on the treatment of stable angina pectoris due to coronary heart disease with Qi-deficiency and blood-stasis syndrome. China Pract. Med. 16 (30), 142–144. 10.14163/j.cnki.11-5547/r.2021.30.056 Guo Z. Yang Z. Song Z. Li Z. Xiao Y. Zhang Y. (2024). Inflammation and coronary microvascular disease: relationship, mechanism and treatment. Front. Cardiovasc. Med. 11, 1280734. 10.3389/fcvm.2024.1280734 38836066 Haijie Y. Changshi L. (2003). Observations on the efficacy of blood-sparing in the treatment of unstable angina pectoris. Pract. J. Rural Dr. 10 (04), 30. 10.3969/j.issn.1672-7185.2003.04.026 Haiqing Y. (2012). Compound leech capsule in the treatment of angina pectoris of coronary heart disease in 112 cases. Guangming J. Chin. Med. 27 (11), 2228–2229. 10.3969/j.issn.1003-8914.2012.11.038 Haiyan H. (2010). Clinical observation on the treatment of angina pectoris of coronary heart disease with self-proposed ginseng and leech soup. J. Liaoning Universtity Traditional Chin. Med. 12 (04), 154–155. 10.13194/j.jlunivtcm.2010.04.156.huanghy.064 Hongying L. Shaojun C. Jing Y. Yong C. Youhe M. (2015). Observation on the efficacy of Astragalus Ginseng and Dan Hirudin Tang in the treatment of unstable angina pectoris. J. Emerg. Traditional Chin. Med. 24 (3), 509–511. 10.3969/j.issn.1004-745X.2015.03.050 Hongying Y. Zhaoping W. Hongmin S. Fang L. Wei L. (2016). Study on the efficacy and safety of Vermicelli and Snake Tongluo Capsules in the treatment of coronary heart disease. Word Latest Med. Inf. 16 (79), 174–74. 10.3969/j.issn.1671-3141.2016.79.145 Hummelgaard S. Vilstrup J. P. Gustafsen C. Glerup S. Weyer K. (2023). Targeting PCSK9 to tackle cardiovascular disease. Pharmacol. Ther. 249, 108480. 10.1016/j.pharmthera.2023.108480 37331523 Jaishankar T. Shivasekar M. Vinodhini V. M. (2023). Endothelial nitric oxide synthase T-786C and G-894T gene polymorphisms: a risk assessment of coronary heart disease. J. Assoc. Physicians India 71 (9), 45–50. 10.59556/japi.71.0294 38700301 Jian F. Xudong L. (2002). Observation on the efficacy of Tongxinluo capsule in the treatment of angina pectoris of coronary heart disease. Acta Acad. Med. Jiangxi 42 (6), 55. 10.3969/j.issn.1000-2294.2002.06.033 Jianmin D. Rong Y. F. Yurong X. Jinghua F. Sui X. Zhe Y. (2016). Effect analysis of Qizhi Tongmai granule in the treatment of coronary heart disease in a multicenter trail. World Clin. Drugs 37 (5), 324–327. 10.13683/j.wph.2016.05.008 Jinbao S. Fang L. Huikang H. (2012). Clinical efficacy observation on the treatment of unstable angina pectoris by blood circulation and pulse circulation capsule. Chin. J. Geriatric Care 10 (4), 23–25. 10.3969/j.issn.1672-4860.2012.04.009 Jing X. Ming G. Dan C. Xin L. (2002). Clinical observation on the treatment of unstable angina pectoris with blood-sparing injection solution. Clin. Focus 17 (06), 338–339. 10.3969/j.issn.1004-583X.2002.06.022 Jinghe S. (2003). Clinical observations on effect of Qishen Capsules on angina pectoris. Chin. Tradit. Pat. Med. 25 (4), 303–304. 10.3969/j.issn.1001-1528.2003.04.014 Jinliang W. Yunyi Z. (2013). Observations on the clinical application of Ginseng Hirudo Pill in the treatment of 156 cases of coronary heart disease angina pectoris of the silt-blood paralysis-obstruction type. Chin. Foreign Med. Res. 11 (3), 39. 10.14033/j.cnki.cfmr.2013.03.008 Jun L. Xiangyun L. Lei Z. (2011). Analysis of the efficacy of Tongxinluo capsule in the treatment of coronary heart disease chronic heart failure. Hebei Med. J. 33 (12), 1892–1893. 10.3969/j.issn.1002-7386.2011.12.085 Junjiang Z. Qingxiang D. Aiqing L. (2004). Clinical observation of coronary heart disease unstable angina pectoris treated by Shu-xue-tong Injection. Pract. Clin. J. Integr. Traditional Chin. West. Med. 04 (06), 15–16. 10.3969/j.issn.1671-4040.2004.06.010 Junren C. Xiaofang X. Huiqiong Z. Gangmin L. Yanpeng Y. Xiaoyu C. (2021). Pharmacological activities and mechanisms of hirudin and its derivatives - a Review. Front. Pharmacol. 12, 660757. 10.3389/fphar.2021.660757 33935784 Kamstrup P. R. (2021). Lipoprotein(a) and cardiovascular disease. Clin. Chem. 67 (1), 154–166. 10.1093/clinchem/hvaa247 33236085 Katta N. Loethen T. Lavie C. J. Alpert M. A. (2021). Obesity and coronary heart disease: epidemiology, pathology, and coronary artery imaging. Curr. Problems Cardiol. 46 (3), 100655. 10.1016/j.cpcardiol.2020.100655 32843206 Kong P. Cui Z. Y. Huang X. F. Zhang D. D. Guo R. J. Han M. (2022). Inflammation and atherosclerosis: signaling pathways and therapeutic intervention. Signal Transduct. Target. Ther. 7 (1), 131. 10.1038/s41392-022-00955-7 35459215 Laiqiang W. (2021). Efficacy of astragalus vermicularis and panax ginseng soup in the treatment of qi deficiency and blood stasis in stable angina pectoris of coronary heart disease. Psychol. Mag. 16 (12), 80–176. 10.19738/j.cnki.psy.2021.12.039 Leilei Z. (2011). Clinical observation on the treatment of angina pectoris of coronary heart disease by compound hirudin essence capsule. J. Guiyang Coll. Traditional Chin. Med. 33 (06), 86–87. 10.3969/j.issn.1002-1108.2011.06.44 Lemke S. Vilcinskas A. (2020). European medicinal leeches-new roles in modern medicine. Biomedicines 8 (5), 99. 10.3390/biomedicines8050099 32349294 Lifang C. Guofeng J. (2005). Clinical observation on the treatment of unstable angina pectoris by leech Ding Yu Si Shen San. J. Emerg. Traditional Chin. Med. 14 (09), 817–818. 10.3969/j.issn.1004-745X.2005.09.005 Linfeng L. (2003). Observation on the efficacy of blood circulation and blood circulation capsule in the treatment of angina pectoris of coronary heart disease. J. Emerg. Traditional Chin. Med. 12 (04), 298–299. 10.3969/j.issn.1004-745X.2003.04.006 Mao Y. Qiang Z. (2017). Clinical analysis of red hirudin in the treatment of unstable angina pectoris. J. Pract. Traditional Chin. Med. 33 (10), 1116–1118. 10.3969/j.issn.1004-2814.2017.10.002 Mao P. Liu X. Weng Y. Tang L. Tang Y. (2021). Clinical efficacy of aspirin combination treatment in the treatment of coronary heart disease and its effect on inflammatory factors: a systematic review and meta-analysis. Ann. Palliat. Med. 10 (8), 8858–8868. 10.21037/apm-21-1648 34488373 Passacquale G. Sharma P. Perera D. Ferro A. (2022). Antiplatelet therapy in cardiovascular disease: current status and future directions. Br. J. Clin. Pharmacol. 88 (6), 2686–2699. 10.1111/bcp.15221 35001413 Pothineni N. V. K. Subramany S. Kuriakose K. Shirazi L. F. Romeo F. Shah P. K. (2017). Infections, atherosclerosis, and coronary heart disease. Eur. heart J. 38 (43), 3195–3201. 10.1093/eurheartj/ehx362 29020241 Qingfan Z. Hezhong X. (2008). Therapeutic efficacy of blood-sparing in the treatment of unstable angina pectoris observed. J. Med. Forum 29 (11), 74–75. 10.3969/j.issn.1672-3422.2008.11.045 Qiu J. Ling-Na W. Qian L. Chun-Miao Y. Yong-Qing Z. (2022). Research progress on processing history evolution, chemical constituents, and pharmacological effects of hirudo. China J. Chin. Materia Medica 47 (21), 5806–5816. 10.19540/j.cnki.cjcmm.20220411.201 Quanyou G. (2011). Observations on the clinical effect of blood-sparing in the treatment of unstable angina pectoris. Contemp. Med. 17 (06), 61–62. 10.3969/j.issn.1009-4393.2011.6.044 Rongxing C. Linlin L. (2009). Interventional effect of Tongxinluo capsule on unstable angina pectoris. Guizhou Med. J. 33 (10), 923–924. 10.3969/j.issn.1000-744X.2009.10.030 Shan-Shan L. Lu H. (2022). Pharmaceutical care for a patient with statin intolerant familial hypercholesterolemia by lipid-lowering strategy. Cent. South Pharm. 20 (01), 209–213. Shaofeng C. Xinfeng Z. (2011). Clinical observation on the treatment of stable angina pectoris with ginseng descending soup. Shanxi Med. J. 40 (10), 1012–1013. 10.3969/j.issn.0253-9926-B.2011.10.030 Shaohua Z. (2004). Clinical study on the treatment of unstable angina pectoris with leech capsule. J. Sichuan Traditional Chin. Med. 22 (04), 34–35. 10.3969/j.issn.1000-3649.2004.04.020 Shaya G. E. Leucker T. M. Jones S. R. Martin S. S. Toth P. P. (2022). Coronary heart disease risk: low-density lipoprotein and beyond. Trends Cardiovasc. Med. 32 (4), 181–194. 10.1016/j.tcm.2021.04.002 33872757 Shiyao L. (2010). Treatment of coronary heart disease with leech and sanshuang tang. China Pract. Med. 5 (25), 148–149. 10.3969/j.issn.1673-7555.2010.25.118 Shougang J. (2005). Clinical observation on the treatment of 50 cases of lability angina pectoris of coronary heart disease with ShenzhiHuoxue Decoction. Guid. J. TCM 11 (5), 8–10. 10.3969/j.issn.1672-951X.2005.05.004 Shugang Y. Yingxuan G. Guohua Y. (2009). Observation of effect of Shuxuetong Injection in treatment of unstable angina pectoris. Med. World 11 (10), 590–591. Su W. Song S. Dong H. Wu H. Meng Z. (2023). Identifying and comparing low-value care recommendations for coronary heart disease prevention, diagnosis, and treatment in the US and China. Int. J. Cardiol. 374, 1–5. 10.1016/j.ijcard.2022.12.031 36566783 Sujuan Y. Haijun G. (2004). 120 cases of coronary heart disease angina pectoris treated with Shu Xin Tong Paralysis Tang. Shaanxi J. Traditional Chin. Med. 25 (07), 586–587. 10.3969/j.issn.1000-7369.2004.07.006 Sujuan Y. Wang F. Lu H. Guofang D. Yinna W. (2014). Observation on the therapeutic effect of 200 cases of angina pectoris in coronary heart disease treated with cardiac pain relief capsule. Chin. J. Integr. Med. Cardio/Cerebrovascular Dis. 2 (13), 190–191. 10.16282/j.cnki.cn11-9336/r.2014.13.005 Sun W. T. Du J. Y. Wang J. Wang Y. L. Dong E. D. (2025). Potential preservative mechanisms of cardiac rehabilitation pathways on endothelial function in coronary heart disease. Sci. China. Life Sci. 68 (1), 158–175. 10.1007/s11427-024-2656-6 39395086 Tangheng Z. (2008). Observation on the therapeutic effect of fu zheng resolving phlegm and dispelling blood stasis soup in the treatment of angina pectoris of coronary heart disease. Chin. Med. Mod. Distance Educ. China 06 (07), 679–680. 10.3969/j.issn.1672-2779.2008.07.034 Taojin L. (2002). Clinical observation on treatment of angina pectoris in coronary heart disease with chrysanthemum and leech soup. Chin. J. Inf. Traditional Chin. Med. 9 (08), 7–10. 10.3969/j.issn.1005-5304.2002.08.004 Tingguo L. Jun C. Junxiang L. (2012). Observation on the clinical efficacy of Yiqi, Blood-breaking and Vein-passing Soup in the treatment of angina pectoris of coronary heart disease. Chin. Community Dr. 14 (18), 245–246. 10.3969/j.issn.1007-614x.2012.18.223 Tong W. Ying S. Guojie H. Liyan L. Hua G. Qingkai W. (2001). Therapeutic effect of leech capsule with compound danshen and astragalus in the treatment of unstable angina pectoris observed. Bull. Med. Res. 30 (03), 56–57. 10.3969/j.issn.1673-548X.2001.03.031 Ueki Y. Itagaki T. Kuwahara K. (2024). Lipid-lowering therapy and coronary plaque regression. J. Atheroscler. Thrombosis. 31 (11), 1479–1495. 10.5551/jat.RV22024 39111840 Violi F. Pignatelli P. Valeriani E. (2024). Oxidative stress and atherosclerosis: basic and clinical open issues. Kardiologia Pol. 82 (7-8), 689–691. 10.33963/v.phj.100994 38845438 Wei H. Bihua Z. Suqiang G. (2013). The clinical effects of Maixuekang capsule on coronary heart disease angina pectoris. China Med. 8 (8), 1051–1052. 10.3760/cma.j.issn.1673-4777.2013.08.005 Weidong N. Lihua G. (2009). Observation of effect of Shuxuetong Injection in treatment of angina pectoris. Med. World 11 (12), 790–791. Wenhua L. Wei Z. Gaoqiao S. Shasha X. Yang Z. (2020). Study on the effect and mechanism of Astragalus membranaceus-leech-pseudo ginseng soup on unstable angina pectoris patients with qi deficiency and phlegm stasis type. Prog. Mod. Biomed. 20 (12), 2396–2400. 10.13241/j.cnki.pmb.2020.12.043 Wenhui F. Shiliang Z. (2019). Clinical efficacy of ginseng vermiculite heart capsule in the adjuvant treatment of stable angina pectoris with qi deficiency and blood stasis and its mechanism. Shandong Med. J. 59 (14), 65–68. 10.3969/j.issn.1002-266X.2019.14.019 Wu L. Gong Y. Wang X. (2001). Clinical observation on the treatment of angina pectoris in coronary heart disease with thrombus cardiac venous capsule. Heilongjiang Yixue 25 (11), 827. Wu S. Zhou Y. Wang Y. Zhang Z. (2024). Therapeutic potentials of medicinal leech in Chinese Medicine. Am. J. Chin. Med. 52 (4), 1027–1051. 10.1142/s0192415x24500423 38879745 Xianming F. Liuhua X. Jianshe Y. (2002). Treatment of coronary heart disease stabilized angina pectoris in 30 cases with Yixinwei granules. Shaanxi J. Traditional Chin. Med. 23 (12), 1092–1093. 10.3969/j.issn.1000-7369.2002.12.029 Xiao-Mei M. (2011). Efficacy observation of zhidan xiaozhi decoction in 60 cases of coronary heart disease of qi and blood stagnation pattern and internal retention of phlegm damp pattern. World J. Integr. Traditional West. Med. 6 (7), 590–597. 10.3969/j.issn.1673-6613.2011.07.014 Xiaojun L. (2010). Analysis of 30 cases of unstable angina pectoris treated with blood-sparing injection. Chin. J. Coal Industry Med. 13 (03), 423. Xiaoyan Y. Bainian G. (2006). Observation on the therapeutic effect of 40 cases of coronary heart disease treated with blood circulation and blood circulation capsule. Tianjin Med. J. 34 (5), 347–348. 10.3969/j.issn.0253-9896.2006.05.028 Xin L. Xinyi O. Yanhong W. Yang L. Haoxuan Z. Li Z. (2023). Effects of different lipid-lowering treatments on ischemic stroke patients with statin intolerance. J. Med. Res. and Combat Trauma Care 36 (05), 473–478. 10.16571/j.cnki.2097-2768.2023.05.005 Xinnian L. Lu L. (2012). Treatment of coronary heart disease and angina pectoris with senxiong hirubai granules in 31 cases. Chin. Med. Mod. Distance Educ. China 10 (7), 27–28. 10.3969/j.issn.1672-2779.2012.07.015 Xuexu S. Li C. Xiuyan Z. (2014). Clinical efficacy of Astragalus Vermiculosus Sanqi Tang in the treatment of stable angina pectoris. China Health Care Nutr. (4), 104–105. Yanbo L. (2014). Observation on the therapeutic effect of Pulse Blood Kang Capsules in treating coronary heart disease angina in middle-aged and old-aged people. Chin. J. Integr. Med. Cardio/Cerebrovascular Dis. 12 (03), 302. 10.3969/j.issn.1672-1349.2014.03.025 Yanhong W. Huixia J. Xiaodong L. (2003). Coronary heart disease of unstable type treated by Tongxinluo Capsule. Shaanxi J. Traditional Chin. Med. 24 (08), 676–678. 10.3969/j.issn.1000-7369.2003.08.002 Yong J. (2010). Analysis of therapeutic efficacy of shuoxiantong in treating unstable angina pectoris in the elderly. Chin. J. Misdiagnostics 10 (25), 6083–83. Yongchao Z. Chunyi Y. Guoxing G. (2011). Treatment of angina pectoris of coronary heart disease with Shen hirudo pill in 40 cases. Chin. Med. Mod. Distance Educ. China 9 (22), 13–14. 10.3969/j.issn.1672-2779.2011.22.007 Youjun Z. (2014). Clinical observation of Shu Xue Tong injection in the treatment of 56 patients with coronary heart disease. Chin. Community Dr. 30 (32), 82–84. 10.3969/j.issn.1007-614x.2014.32.49 Yu S. (2013). Clinical observation on the treatment of unstable angina pectoris in the elderly with blood-sparing injection solution. Contin. Med. Educ. 27 (03), 51–52+65. 10.3969/J.ISSN.1004-6763.2013.03.016 Yunhai C. (2009). Treatment of coronary heart disease with leech and sanshuang tang. Guangming J. Chin. Med. 24 (06), 1081–1083. 10.3969/j.issn.1003-8914.2009.06.054 Yuxia Z. Jing Y. Zhonghua C. (2002). Effects of quyu xiaoban Capsule on blood lipid Level and platelet activity in coronary heart disease. J. Guangzhou Univ. Traditional Chin. Med. 19 (3), 172–174. 10.3969/j.issn.1007-3213.2002.03.003 Zehong Z. Zuyun Z. Linxiang F. Mingxiang H. Jingyuan L. Weidong O. (2002). Effect of buxin huoluo capsule for coronary heart disease and its anti-lipid-peroxidation mechanism. J. Guangzhou Univ. Traditional Chin. Med. 19 (2), 85–87. 10.3969/j.issn.1007-3213.2002.02.001 Zhang X. Yan Q. Jiang J. Luo H. Ren Y. (2024). Safety and efficacy of aspirin and indobufen in the treatment of coronary heart disease: a systematic review and meta-analysis. Front. Cardiovasc. Med. 11, 1412944. 10.3389/fcvm.2024.1412944 39211768 Zhaomei D. Lian X. (2015). Clinical study on the treatment of stable angina pectoris with qi deficiency and blood stasis by astragalus vermicularis and saffron soup. Chin. J. Integr. Med. Cardio/Cerebrovascular Dis. 13 (1), 95–96. 10.3969/j.issn.16721349.2015.01.035 Zhi-Min Z. Yan-Xia G. Huai-Lin L. Yi-Qiang Y. Li Y. (2006). Wentongjian in prevented coronary restenosis of percutaneous coronary intervention. Chin. J. Arteriosclerosis 14 (7), 610–612. 10.3969/j.issn.1007-3949.2006.07.016 Zhijing L. Shufeng H. Yingchun L. Xiaojuan S. Ruiling M. Jinchun S. (2016). Dialectical treatment of angina pectoris in coronary heart disease by Shandan Guanxin group formulae. Word Latest Med. Inf. 16 (41), 152–153. 10.3969/j.issn.1671-3141.2016.41.121 Zhixue T. Baicheng Q. Baoliang W. (2017). Clinical study of yiqi huayu decoction in treatment of coronary heart disease angina pectoris with phlegm and blood stasis syndrome China. J. Chin. Med. 32 (7), 1251–1253. 10.16368/j.issn.1674-8999.2017.07.329 Zhongtian X. Rihui D. (2001). Efficacy observation of 52 cases of unstable angina pectoris treated with self-proposed piper betel vermicompost soup. Clin. J. Traditional Chin. Med. 13 (1), 34–35. 10.3969/j.issn.1672-7134.2001.01.018 Zongsheng D. (2013). Clinical observation on the treatment of unstable angina pectoris with blood stasis and paralysis closure by leech and safflower soup. Hubei J. Traditional Chin. Med. 35 (03), 37–38. 10.3969/j.issn.1000-0704.2013.03.017