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Journal of Traditional Chinese Medicine logoLink to Journal of Traditional Chinese Medicine
. 2023 May 6;43(4):640–649. doi: 10.19852/j.cnki.jtcm.20230506.001

Effect of Traditional Chinese Medicine combined with Western Medicine on blood lipid levels and inflammatory factors in patients with angina pectoris in coronary heart disease identified as intermingled phlegm and blood stasis syndrome: a network Meta-analysis

Chao WANG 1,2, Qiong WU 3, Ping LI 4, Zhigang WANG 5, Xusheng LOU 4, Yuanyuan LI 4, Lin ZHANG 6,✉
PMCID: PMC10320448  PMID: 37454248

Abstract

OBJECTIVE

To evaluate the clinical efficacy of Traditional Chinese Medicine prescriptions for resolving phlegm in the treatment of angina pectoris of phlegm-stasis coronary heart disease by a network Meta-analysis.

METHODS

Randomized controlled trials (RCTs) on clinical efficacy of CHD angina pectoris with interaction of phlegm and blood stasis were searched in PubMed, Springer, the Cochrane Library and Chinese-language databases China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Data from their inception to December 2021. Literature was screened and literature bias risk was assessed by RevMan5.4 software. The overall response rate, the duration of angina attack, the levels of serum lipids such as total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C), and expression of hypersensitive C-reactive protein (hs-CRP) were selected as outcome indicators for network Meta-analysis and mapped using Stata15.1 software.

RESULTS

Totally, 26 RCTs were included, involving 2098 participants. There were 6 TCM formulas with the effects of dispelling phlegm and removing blood stasis. Taking conventional Western Medicine as the common intervention measures, the results showed that the overall response improvement rate from high to low was displayed as modified Xiaoxianxiong decoction (小陷胸汤, MXD), Danlou tablet (丹蒌片, DT), modified Gualou Xiebai Banxia decoction (瓜蒌薤白半夏汤, MGXBD), modified Wendan decoction (温胆汤, MWD), modified Zhishi Xiebai Guizhi decoction (枳实薤白桂枝汤, MZXGD), and modified Erchen decoction (二陈汤, MED). The sequence of angina attack duration improvement from high to low was MZXGD, MGXBD, DT, MWD, MXD. The sequence of TC improvement from high to low was MZXGD, MED, DT, and MGXBD. Sequence of improving TG from high to low was MED, MZXGD, MGXBD, and DT. For LDL-C improvement, the effect from good to poor was MZXGD, MGXBD, DT, and MED. With regard to HDL-C improvement, the effect was ranked as MED, MZXGD, MGXBD, and DT from good to poor. hs-CRP expression from high to low was MZXGD, MXD, MED, MWD, and MGXBD.

CONCLUSION

TCM formula with the effects of dispelling phlegm and removing blood stasis combined with conventional Western Medicine has obvious advantages in treating CHD angina pectoris with interaction of phlegm and blood stasis. MZXGD has great potential in increasing the overall response rate, reducing Duration of angina attack improving blood lipids, and reducing inflammatory factors. However, due to the limitations of extant studies, the conclusions of this study need to be confirmed by numerous reasonably-designed RCTs.

Keywords: coronary disease; angina pectoris; phlegm and blood stasis interaction; blood lipid; inflammatory factors; medicine, traditional Chinese; network Meta-analysis; randomized controlled trial

1. INTRODUCTION

Coronary heart disease (CHD) angina pectoris is a clinical syndrome mainly manifested by paroxysmal chest pain caused by myocardial ischemia and hypoxia due to insufficient coronary artery blood supply.1 It belongs to the category of Xiong Bi and heartache in Traditional Chinese Medicine (TCM). The pathogenesis is the deficiency of the root and excess of the biao. For example, the deficiency of heart Qi, blood, Yin, Yang or both heart Qi and Yin deficiency with the excess of blood stasis, phlegm, Qi stagnation or cold coagulation are the main leading causes.2 Clinical epidemiological investigation of TCM syndromes of CHD revealed that phlegm and blood stasis were one of the most common syndromes.3 Research shows that phlegm and blood stasis are the etiology and pathogenesis of CHD.4 Blood stasis exists in the whole process of the occurrence and development of CHD. Blood stasis can lead to abnormal metabolism of water, resulting in water and fluid retention and phlegm ensues. Studies have found that the incidence of phlegm turbidity and blood stasis syndrome in CHD is positively correlated with the increase of serum concentrations of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and triglyceride (TG).5 Dyslipidemia may be an important pathological basis of phlegm-turbid blood-stasis CHD. TCM plays an irreplaceable role in the prevention and treatment of phlegm and stasis. Increased hypersensitive C-reactive protein (hs-CRP) is one of the serological markers of inflammation, and hs-CRP can also directly gets involved in the formation and progression of atherosclerosis through various mechanisms. Therefore, its level can be used as the basis of diagnosis and condition judgment of CHD.6

There are nearly dozens of TCM prescriptions to treat CHD angina pectoris with phlegm and blood stasis. Most of the studies were randomized controlled trials (RCTs), perhaps with Chinese herbal formula alone compared to conventional Western Medicine in a double arm design. Comparative studies between different TCM prescriptions are lacking. The sample size is usually small for this kind of clinical studies. To overcome the shortcoming, network Meta-analysis was used by ranking the effects of different interventions after direct and indirect evidence comparisons.7 Therefore, in this study, we conducted a network Meta-analysis on the efficacy of TCM prescriptions in the treatment of CHD angina pectoris by dispelling phlegm and removing blood stasis, and ranked them in order to provide evidence for clinical medication. In addition, there are few Chinese patent medicines treating CHD angina pectoris with the focus on simultaneous of removing phlegm and blood stasis. This study may provide reference and evidence-based medical evidence for CHD with phlegm and blood stasis.

2. METHODS

2.1. Search strategy

We systematically searched English-language databases (PubMed, Springer, the Cochrane Library) and Chinese- language databases China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Data. The retrieval period was from their inception to December 2021. The PubMed search strategy was as follows:

#1 CHD [MeSH Terms] “OR” Coronary heart disease [Title/Abstract] “OR” Coronary heart disease angina pectoris [Title/Abstract]"

#2 Wendan decoction [Title/Abstract] “OR” Erchen decoction [Title/Abstract] “OR” Zhishi Xiebai Guizhi decoction [Title/Abstract] “OR” Gualou Xiebai Banxia decoction [Title/Abstract] “OR” Xiaoxianxiong decoction [Title/Abstract] “OR” Danlou Tablet [Title/Abstract] "OR" Phlegm and blood stasis “OR” Phlegm and stasis treatment [Abstract/Title]"

#3 Randomized controlled trial [Publication Type] “OR” Controlled Clinical Trial [Publication Type] “OR” random [All Fields]

#4 #1 AND #2 AND #3

2.2. Selection criteria

The inclusion criteria were as follows: (a) Study type: RCT of TCM in the treatment of CHD angina pectoris without language or blinding restrictions. (b) Subjects: patients diagnosed with CHD angina pectoris according to clinical standards. In addition, it conforms to the criteria of Naming and Diagnosis of Ischemic Heart Disease8 and Guiding Principles of Clinical Research of Traditional Chinese Medicine New Drugs9 for the diagnosis of CHD angina pectoris identified as phlegm turbidity obstruction manifested as chest tightness or pain, overweight or obesity, fatigue, loose stools, greasy tongue coating or slippery pulse. No age, sex, or race restrictions. (c) Intervention measures: all subjects were given secondary preventive drugs for CHD (mainly including anti-platelet aggregation drugs, nitrates, β-receptor blockers, and calcium channel blockers.). In the experimental group, on the basis of conventional Western Medicine, the classical formula based on phlegm and blood stasis was adopted. The control group received conventional Western Medicine alone. (d) Outcome indicators: any outcome indicators would be included in the network Meta-analysis.

The exclusion criteria included (a) Review, conference paper, theoretical discussion, experience introduction, doctoral and master thesis, and repeated thesis. (b) In the experimental group, other therapies were used in addition to the same treatment of phlegm and blood stasis. (c) The original literature reports were unclear, and the sample number was less than 30 cases. (d) To ensure the literature quality of the study, Chinese literature sources other than Statistical Source Journal of Chinese Science and Technology Papers (CSTPCD), Chinese Social Sciences Citation Index (CSSCI), Peking University Core and China Core Journal Selection database are not included.

2.3. Outcome indicators

We abided by the symposium on the treatment of CHD angina pectoris and arrhythmia by integrated Traditional Chinese and Western Medicine, the evaluation standard of CHD angina pectoris and electrocardiogram,10 and guiding principles of clinical research on the treatment of CHD angina pectoris by Chinese medicine new drugs.11 The outcome indicators include the overall response rate, duration of angina attack, TC, TG, LDL-C, high density lipoprotein cholesterol (HDL-C), and expression of hs-CRP.

2.4. Literature screening and information extraction

Two researchers (WANG Chao and WU Qiong) searched the literature independently. Read the full text of literature that may meet the inclusion criteria. If there is any disagreement, it can be resolved through discussion or contact the original author and consult relevant experts. All the selected literature were input into e-study software for electronic duplicate checking. The information included in Excel was extracted: title, first author, publication time, sample size, average age, male/female ratio, course of disease, comorbidities, diagnostic criteria, interventions, courses of treatment, trials related to literature quality evaluation, and outcome indicators.

2.5. Risk of bias assessment

The included literature was evaluated fairly and impartially using the risk of bias tool recommended by the Cochrane Collaboration. Evaluation contents include: (a) random sequence generation; (b) distribution hidden; (c) study and subject blindness; (d) results evaluator blind method; (e) incomplete outcome; (f) selective reporting; (g) bias from other sources.12 The quality of each study was assessed independently by two researchers (WANG Chao and LI Yuanyuan), and differences were discussed by a third party (WANG Zhigang). Finally, RevMan 5.4 software was used to represent the bias risk graph.

2.6. Data analysis

A network Meta-analysis was conducted using frequency theory in a multivariate framework. Stata15.1 software (StataCorp LLC., College Station, TX, USA) was used to perform statistical analysis on network and mvmeta, which were developed based on multiple regression theory. Odd ratio (OR) and mean difference (MD) were used as effect analysis statistics for dichotomous variables OR continuous variables, respectively. 95% confidence intervals (CIs) were provided by each effect. Among them, 95% CIs of OR value excluding effect line 1 or 95% CIs of MD excluding effect line 0 were considered statistically significant.13 Stata 15.1 software was used to draw a network diagram for comparison between interventions. The size of the dot represents the sample size, and the thickness of the line represents the number of studies included. A comparative-correction funnel plot was drawn to evaluate publication bias. If all points in the figure are evenly and symmetrically distributed and concentrated in the middle and upper parts, it indicates that publication bias or small sample effect is small. The ranking results of various interventions were obtained by calculation, and the cumulative probability ranking chart was drawn. The area value under the curve was obtained, and cluster analysis of the outcome index was conducted based on surface under the cumulative ranking curve (SUCRA) value to obtain the relatively best intervention among the two cluster indicators.14

3. RESULTS

3.1. Characteristics of the included studies

A total of 907 related records were preliminarily searched, and 26 texts were finally included after gradually screening based on the inclusion and exclusion criteria, all of which were Chinese literatures. The literature search and selection are shown in Figure 1.

Figure 1. Literature search and selection.

Figure 1

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CNKI: China National Knowledge Infrastructure; VIP: China Science and Technology Journal Database.

Six formulas for phlegm and blood stasis treatment were used in 32 articles. There were 26 RCTs all in double-arm design15-40 involving 2098 patients. Among them, there were 1047 cases in the control group and 1051 cases in the treatment group. Among these formulas for simultaneous treatment of phlegm and blood stasis, the main formula of modified Wendan decoction (温胆汤, MWD) was in 4 trails,15,⇓,⇓-18 modified Xiaoxianxiong decoction (小陷胸汤, MXD) in 2,19,20 modified Gualou Xiebai Banxia decoction (瓜蒌薤白半夏汤, MGXBD) in 7,21,⇓,⇓,⇓,⇓,⇓,⇓- 28 modified Erchen decoction (二陈汤, MED) in 3,29,⇓-31 modified Zhishi Xiebai Guizhi decoction (枳实薤白桂枝汤, MZXGD) in 5,32,⇓,⇓,⇓- 36 and Danlou tablet (丹蒌片, DT) in 4.37,⇓,⇓-40 The control group was treated with conventional Western Medicine (CWM). Basic characteristics of the included literatures are shown in Table 1.

Table 1.

Basic characteristics of included studies

Included study Sample size (n) Follow-up time (weeks) Intervention Measures number Outcome indicator
T (Male/Female) C (Male/Female) T C T C
Diao YJ et al 202015 35 (19/16) 35 (17/18) 4 MWD+CWM CWM 2 1 ①②
Wang ZG et al 201716 40 (24/16) 40 (22/18) 4 MWD+CWM CWM 2 1 ①
Li FG et al 201717 40 (21/19) 40 (17/23) 12 MWD+CWM CWM 2 1 ①
Luo G,Ye HL 201718 30- 30- 4 MWD+CWM CWM 2 1 ②⑦
Hou BS et al 201819 30 (18/12) 30 (19/11) 2 MXD+CWM CWM 3 1 ①
Guan F et al 201820 50 (29/21) 50 (34/16) 4 MXD+CWM CWM 3 1 ②⑦
Ou XX et al 202121 82 (43/39) 80 (41/39) 2 MGXBD+CWM CWM 4 1 ③④⑤⑥
Qiu WF, Luo JQ 202122 42 (23/19) 42 (21/21) 4 MGXBD+CWM CWM 4 1 ②
Tian PP et al 202123 40 (24/16) 40 (26/14) 4 MGXBD+CWM CWM 4 1 ①③④⑤⑥⑦
Gong XT et al 202124 35 (23/12) 35 (24/11) 4 MGXBD+CWM CWM 4 1 ①③④⑤⑥
Hu XQ 202025 57 (35/22) 57 (39/18) 4 MGXBD+CWM CWM 4 1 ①③④⑤⑥⑦
Wang M et al 202026 80 (44/36) 80 (42/38) 4 MGXBD+CWM CWM 4 1 ①③④⑤⑥
Zhu R et al 202027 42 (25/17) 42 (26/16) 4 MGXBD+CWM CWM 4 1 ①⑦
Xu JJ et al 201728 48 (26/22) 48 (24/24) 4 MGXBD+CWM CWM 4 1 ①②③④⑤⑥⑦
Dong LG et al 202129 48 (23/25) 48 (22/26) 16 MED+CWM CWM 5 1 ②③④⑤⑥
Hu F et al 202130 38 (20/18) 38 (21/17) 12 MED+CWM CWM 5 1 ①②③④⑤⑥
Bai YM,
Huang L 201931 		40 (22/18) 40 (22/19) 4 MED+CWM CWM 5 1 ③④⑤⑥
Yuan QY et al 202132 81 (48/33) 80 (46/34) 2 MZXGD+CWM CWM 6 1 ①⑦
Li FT et al 202133 34 (19/15) 34 (18/16) 8 MZXGD+CWM CWM 6 1 ①②
Li M et al 202134 35- 35- 4 MZXGD+CWM CWM 6 1 ①③④⑤⑥
Tan XD et al 201935 51 (32/19) 51 (34/17) 4 MZXGD+CWM CWM 6 1 ①③④⑤
Liu Y et al 201836 73 - 72- 4 MZXGD+CWM CWM 6 1 ①③④⑤⑥
Zhai H et al 201937 52 (33/19) 52 (32/20) 6 DT+CWM CWM 7 1 ①
Yang K 201938 33 (19/14) 33 (17/16) 52 DT+CWM CWM 7 1 ①⑦
Zhang JH et al 201839 45 (22/23) 45 (24/21) 6 DT+CWM CWM 7 1 ③④⑤⑥
Chen JF et al 201840 98 (57/42) 99 (54/44) 4 DT+CWM CWM 7 1 ①
Diao YJ et al 202041 35 (19/16) 35 (17/18) 4 MWD+CWM CWM 2 1 ②
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Notes: -: unclear; T: treatment group; C: control group. MXD: modified Xiaoxianxiong decoction; DT: Danlou tablet; MGXBD: modified Gualou Xiebai Banxia decoction; MWD: modified Wendan decoction; MZXGD: modified Zhishi Xiebai Guizhi decoction; MED: modified Erchen decoction; CWM: Conventional Western Medicine. ①overall response rate; ② hypersensitive C-reactive protein; ③total cholesterol; ④triglyceride; ⑤low-density lipoprotein cholesterol; ⑥high-density lipoprotein cholesterol; ⑦duration of angina attack.

3.2. Risk of bias

For random sequence generation, randomness was mentioned in all 26 RCTs. Among them, random number table method was used in 20 trials,15,⇓,⇓-18,21,⇓,⇓,⇓,⇓-26,28,29,32,⇓,⇓-35,38 computer random grouping software was used in 1 trial,27 and lottery method was used for 1 trial30 which was rated as low risk. One trial was assigned the order of admission or outpatient service,36 and was rated as high risk of bias. The rest were only described as random and rated as unclear risk. Randomly assigned hidden study, subject blind method and results evaluator blind method which are not described in details in the articles were rated as unclear risk. All articles with complete data and no selective reports were rated as low risk. Unable to judge other sources of bias, it is judged as unclear risk. Supplementary Figure 1 illustrate the risk bias assessment for included studies.

3.3. Results of network Meta-analysis

The overall response rate evidence network diagram shows that 19 included studies15-17,19,23-28,30,32-38,40 reported the overall response rate of TCM prescriptions for removing phlegm and blood stasis in the treatment of CHD angina pectoris. There are six primary Chinese medicine prescriptions. The network relationship between interventions is shown in Figure 2A. The size of the dot represents the sample size, and the thickness of the line represents the number of studies included. The outcome indexes were all reflected in the star structure formed with Western Medicine as the center, without forming a triangular closed ring, which required no consistency test. Results of network Meta-analysis showed that compared to the control group, MWD [OR = 0.29, 95% CI (0.13, 0.65)], MGXBD [OR = 0.27, 95% CI (0.17, 0.45)], MED [OR = 0.29, 95% CI (0.09, 0.92)], MZXGD [OR = 0.28, 95% CI (0.17, 0.47)] and DT [OR = 0.25, 95% CI (0.13, 0.49)] combined with conventional Western Medicine were better than the control group with statistical significance (P < 0.05; Table 2). The overall response rate (SUCRA value) of the six TCM prescriptions was as follows: MXD (70.2%) > DT (61.5%) > MGXBD (56.4%) > MWD (54%) > MZXGD (53.8%) > MED (53.4%) (Figure 3A).

Figure 2. Network evidence results.

Figure 2

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A: overall response rate; B: hs-CRP expression; C: TC; D: TG; E: LDL-C; F: HDL-C; G: duration of angina attack. MXD: modified Xiaoxianxiong decoction; DT: Danlou tablet; MGXBD: modified Gualou Xiebai Banxia decoction; MWD: modified Wendan decoction; MZXGD: modified Zhishi Xiebai Guizhi decoction; MED: modified Erchen decoction; CWM: Conventional Western Medicine. hs-CRP: hypersensitive C-reactive protein; TC: total cholesterol; TG: triglyceride; LDL-C: low density lipoprotein cholesterol; HDL-C: high density lipoprotein cholesterol.

Table 2.

Network Meta-analysis comparisons of overall response rate (lower left) vs hs-CRP (upper right) (OR/MD value vs 95% CI)

CWM 0.66 (0.10, 1.22)a 1.98 (1.26, 2.70)a 0.43 (0.06, 0.79)a 1.89 (1.46, 2.33)a 3.02 (2.32, 3.72)a —
0.29 (0.13, 0.65)a MWD 1.32 (0.41, 2.23)a -0.23 (-0.90, 0.44) 1.23 (0.52, 1.94)a 2.36 (1.46, 3.26)a —
0.20 (0.04, 1.02) 0.69 (0.11, 4.34) MXD -1.55 (-2.36, -0.75)a -0.09 (-0.93, 0.75) 1.04 (0.04, 2.04)a —
0.27 (0.17, 0.45)a 0.96 (0.37, 2.49) 1.39 (0.25, 7.74) MGXBD 1.46 (0.90, 2.03)a 2.59 (1.80, 3.38)a —
0.29 (0.09, 0.92)a 1.02 (0.25, 4.22) 1.48 (0.20, 11.09) 1.07 (0.30, 3.75) MED 1.13 (0.30, 1.95)a —
0.28 (0.17, 0.47)a 0.99 (0.37, 2.61) 1.43 (0.26, 8.06) 1.03 (0.51, 2.11) 0.97 (0.27, 3.42) MZXGD —
0.25 (0.13, 0.49)a 0.89 (0.31, 2.56) 1.29 (0.22, 7.63) 0.93 (0.41, 2.13) 0.87 (0.23, 3.30) 0.90 (0.39, 2.08) DT
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Notes: MXD: modified Xiaoxianxiong decoction; DT: Danlou tablet; MGXBD: modified Gualou Xiebai Banxia decoction; MWD: modified Wendan decoction; MZXGD: modified Zhishi Xiebai Guizhi decoction; MED: modified Erchen decoction; CWM: Conventional Western Medicine. hs-CRP: hypersensitive C-reactive protein; OR: odd ratio; MD: mean difference; CI: confidence interval. aP < 0.05.

Figure 3. Area under the curve ranking results.

Figure 3

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A: overall response rate; B: hs-CRP expression; C: TC; D: TG; E: LDL-C; F: HDL-C; G: duration of angina attack. MXD: modified Xiaoxianxiong decoction; DT: Danlou tablet; MGXBD: modified Gualou Xiebai Banxia decoction; MWD: modified Wendan decoction; MZXGD: modified Zhishi Xiebai Guizhi decoction; MED: modified Erchen decoction; CWM: Conventional Western Medicine. hs-CRP: hypersensitive C-reactive protein; TC: total cholesterol; TG: triglyceride; LDL-C: low density lipoprotein cholesterol; HDL-C: high density lipoprotein cholesterol.

The hs-CRP expression evidence network diagram shows that 8 studies15,18,20,22,28-30,33 reported the expression of hs-CRP in patients with CHD angina pectoris before and after treatment with 5 TCM prescriptions of removing phlegm and blood stasis. The network relationship between interventions is shown in Figure 2B. The results of network Meta-analysis shows that compared with the control group, MWD [MD = 0.66, 95% CI (0.10, 1.22)], MXD [MD = 1.98, 95% CI (1.26, 2.7)], MGXBD [MD = 0.43, 95% CI (0.06, 0.79)], MED [MD = 1.89, 95% CI (1.46, 2.33)] and MZXGD [MD = 3.02, 95% CI (2.32, 3.72)] combined with conventional Western Medicine were better than the control group with statistical significance (P < 0.05). In addition, on the different TCM prescriptions to improve the expression of hs-CRP, MWD compared with MXD [MD = 1.32, 95% CI (0.41, 2.23)], MED [MD = 1.23, 95% CI (0.52, 1.94)], MZXGD [MD = 2.36, 95% CI (1.46, 3.26)], MXD compared with MGXBD [MD = —1.55, 95% CI (—2.36, —0.75)], MZXGD [MD = 1.04, 95% CI (0.04, 2.04)], MGXBD compared with MED [MD = 1.46, 95% CI (0.9, 2.03)], MZXGD [MD = 2.59, 95% CI (1.8, 3.38)], MED compared with MZXGD [MD = 1.13, 95% CI (0.30, 1.95)] with statistical significance (P < 0.05; Table 2).The sequence of hs-CRP expression (SUCRA value) was as follows: MZXGD (99.6%) > MXD (71.9%) > MED (68.4%) > MWD (34.7%) > MGXBD (24.9%) (Figure 3B).

The improvement of TC evidence network diagram shows that the 14 studies21,23-26,28-31,34-37,39 reported the TC improvement of 4 TCM prescriptions of removing phlegm and blood-stasis on patients with CHD angina pectoris. The network relationship between interventions is shown in Figure 2C. Results of network Meta-analysis showed that compared with the control group, MGXBD [MD = 0.73, 95% CI (0.21, 1.24)], MED [MD = 0.89, 95% CI (0.18, 1.61)], MZXGD [MD = 1.41, 95% CI (0.68, 2.14)] combined with conventional Western Medicine were better than the control group with statistical differences (P < 0.05; Table 3). The order of TC improvement (SUCRA value) was modified ZXGD (89.8%) > MED (59.3%) > DT (49.6%) > MGXBD (47.7%) (Figure 3C).

Table 3.

Network Meta—analysis comparisons of TC (lower left) vs TG (upper right) (MD value vs 95% CI)

CWM 0.49 (0.12, 0.86)a 1.23 (0.72, 1.75)a 1.16 (0.62, 1.71)a 0.33 (—0.55, 1.21)
0.73 (0.21, 1.24)a MGXBD 0.74 (0.11, 1.38)a 0.68 (0.02, 1.33)a —0.16 (—1.11, 0.80)
0.89 (0.18, 1.61)a 0.17 (—0.72, 1.05) MED —0.07 (—0.82, 0.68) —0.90 (—1.92, 0.12)
1.41 (0.68, 2.14)a 0.68 (—0.21, 1.58) 0.52 (—0.51, 1.54) MZXGD —0.83 (—1.87, 0.20)
0.76 (—0.48, 2.00) 0.03 (—1.31, 1.38) —0.13 (—1.57, 1.30) —0.65 (—2.10, 0.79) DT
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Notes: DT: Danlou tablet; MGXBD: modified Gualou Xiebai Banxia decoction; MZXGD: modified Zhishi Xiebai Guizhi decoction; MED: modified Erchen decoction; CWM: Conventional Western Medicine; TC: total cholesterol; TG: triglyceride; MD: mean difference; CI: confidence interval. aP < 0.05.

The improvement of TG evidence network diagram shows that the 13 studies21,23-26,28-31,34-36,39 reported the improvement of TG in patients with CHD angina pectoris by 4 TCM prescriptions of removing phlegm and blood stasis. The network relationship between interventions is shown in Figure 2D. Results of network Meta-analysis showed that compared with the control group, MGXBD [MD = 0.49, 95% CI (0.12, 0.86)], MED [MD = 1.23, 95% CI (0.72, 1.75)], MZXGD [MD = 1.16, 95% CI (0.62, 1.71)] combined with conventional Western Medicine were better than the control group with statistical significance (P < 0.05). In addition, on the different TCM prescriptions to improve the TG, MGXBD compared with MED [MD = 0.74, 95% CI (0.11, 1.38)] and MZXGD [MD = 0.68, 95% CI (0.02, 1.33)], and there were statistically significant differences (P < 0.05; Table 3). The sequence of TG improvement (SUCRA value) was MED (87.9%) > MZXGD (83.9%) > MGXBD (41.4%) > DT (30.8%) (Figure 3D).

The improvement of LDL-C evidence network diagram shows that the 13 studies21,23-26,28-31,34-36,39 reported the improvement of LDL-C in patients with CHD angina pectoris with 4 kinds of TCM prescriptions for removing phlegm and blood stasis. The network relationship between interventions is shown in Figure 2E. Results of network Meta-analysis showed that compared with the control group, MGXBD [MD = 0.66, 95% CI (0.34, 0.98)], MED [MD = 0.51, 95% CI (0.06, 0.96)], MZXGD [MD = 1.00, 95% CI (0.52, 1.48)] combined with conventional Western Medicine were better than the control group with statistical significance (P < 0.05; Table 4).The order of LDL-C improvement (SUCRA value) was MZXGD (89.5%) > MGXBD (57.8%) > DT (57.4%) > MED (43.7%) (Figure 3E).

Table 4.

Network Meta—analysis comparisons of LDL—C (lower left) vs HDL—C (upper right) (MD value vs 95% CI)

CWM —0.17 (—0.27, —0.07)a —0.47 (—0.60, —0.34)a —0.23 (—0.46, —0.01)a —0.05 (—0.25, 0.15)
0.66 (0.34, 0.98)a MGXBD —0.30 (—0.47, —0.14)a —0.06 (—0.31, 0.18) 0.12 (—0.10, 0.35)
0.51 (0.06, 0.96)a —0.14 (—0.69, 0.41) MED 0.24 (—0.02, 0.50) 0.42 (0.19, 0.66)a
1.00 (0.52, 1.48)a 0.34 (—0.24, 0.92) 0.49 (—0.17, 1.15) MZXGD 0.18 (—0.12, 0.48)
0.66 (—0.10, 1.42) 0.00 (—0.82, 0.83) 0.15 (—0.73, 1.03) —0.34 (—1.24, 0.56) DT
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Notes: DT: Danlou tablet; MGXBD: modified Gualou Xiebai Banxia decoction; MZXGD: modified Zhishi Xiebai Guizhi decoction; MED: modified Erchen decoction; CWM: Conventional Western Medicine. LDL-C: low density lipoprotein cholesterol; HDL-C: high density lipoprotein cholesterol; MD: mean difference; CI: confidence interval. aP < 0.05.

The improvement of HDL-C evidence network diagram shows that the 13 studies21,23-26,28-31,34-36,39 reported the improvement of HDL-C in patients with CHD angina pectoris by 4 kinds of TCM prescriptions with the effect of removing phlegm and blood stasis. The network relationship between interventions is shown in Figure 2F. Results of network Meta-analysis showed that compared with the control group, MGXBD [MD = — 0.17, 95% CI (— 0.27, — 0.07)], MED [MD = — 0.47, 95% CI (— 0.60, — 0.34)], MZXGD [MD = — 0.23, 95% CI (— 0.46, — 0.01)] combined with conventional Western Medicine were better than the control group with statistical significance (P < 0.05). In addition, on the different TCM prescriptions to improve the HDL-C, MGXBD compared with MED [MD = — 0.30, 95% CI (— 0.47, — 0.14)], and MED compared with DT [MD = 0.42, 95% CI (0.19, 0.66)], and there were statistically significant differences (P < 0.05; Table 4).The improvement of HDL-C (SUCRA value) was as follows: MED (99.2%) > MZXGD (64.6%) > MGXBD (54%) > DT(24.1%) (Figure 3F).

The evidence network diagram shows that the eight included studies18,20,23,25,27-28,32,38 reported the duration of the onset of angina attack in the treatment of coronary heart disease with phlegm dissolving and stasis removing herbal prescriptions. There were five main Chinese medicine prescriptions, and the network relationship between the interventions was shown in Figure 2G. The results of network Meta-analysis showed that MGXBD [MD = 1.54, 95% CI (1.00, 2.07)] and MZXGD [MD = 2.14, 95% CI (1.09, 3.19)] combined with conventional western medicine were better than those of the control group. The difference was statistically significant (P < 0.05). In addition, in terms of improving the duration of angina attack, MXD was compared with MGXBD [MD = 2.03, 95% CI (0.44, 3.62)] and MZXGD [MD = 2.63, 95% CI (0.80, 4.46)] (P < 0.05; Table 5). The sequence of duration of angina attack (SUCRA value) was as follows: MZXGD (94.3%) > MGXBD (77.2%) > DT (54.3%) > MWD (49.5%) > MXD (7.6%) (Figure 3G).

Table 5.

Network Meta—analysis comparisons of duration of angina attack (MD value vs 95% CI)

CWM
0.85 (—0.18, 1.88) MWD
—0.49 (—1.98, 1.00) —1.34 (—3.16, 0.48) MXD
1.54 (1.00, 2.07)a 0.69 (—0.48, 1.85) 2.03 (0.44, 3.62)a MGXBD
2.14 (1.09, 3.19)a 1.29 (—0.18, 2.76) 2.63 (0.80, 4.46)a 0.60 (—0.58, 1.78) MZXGD
0.97 (—0.11, 2.05) 0.12 (—1.38, 1.62) 1.46 (—0.38, 3.30) —0.57 (—1.78, 0.64) —1.17 (—2.68, 0.34) DT
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Notes: MXD: modified Xiaoxianxiong decoction; DT: Danlou tablet; MGXBD: modified Gualou Xiebai Banxia decoction; MWD: modified Wendan decoction; MZXGD: modified Zhishi Xiebai Guizhi decoction; CWM: Conventional Western Medicine; MD: mean difference; CI: confidence interval. aP < 0.05.

3.4. Publication bias and small sample effect

A comparative-corrected funnel plot was drawn using the number of studies included and the overall response rate and TC with more interventions as outcome indicators. As shown in Figure 4, dots in different colors in the figure represent direct comparison of different two interventions. The distribution of funnel plot is roughly symmetrical, and there is a certain angle between the calibration auxiliary line and the center line, indicating publication bias or small sample events.

Figure 4. Comparison-correction funnel plot of clinical effects.

Figure 4

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3.5. Cluster analysis

The overall response rate was analyzed by clustering with TC, TG, LDL-C, hs-CRP and duration of angina attack. Cluster analysis was performed on TC and LDL-C (supplementary Figure 2). In the included studies, TCM with the effects of removing phlegm and blood stasis combined with conventional Western Medicines were dominant in the ranking of various outcome indicators. Among them, MZXGD showed the best performance in improving the overall response rate, TC, LDL-C, hs-CRP and duration of angina attack simultaneously. Both MED and MZXGD improved the overall response rate and TG expression. MZXGD had the best effect on improving TC and LDL-C simultaneously.

4. DISCUSSION

The pathogenesis of CHD angina pectoris is the occurrence of atherosclerosis in coronary arteries caused by various factors, resulting in vascular obstruction, which further affects the blood supply of myocardium of the body, showing symptoms of myocardial ischemia such as angina pectoris. If the condition is not controlled in time, it may lead to serious diseases such as myocardial infarction. Western Medicine believes that abnormal metabolism of blood lipids, increased blood viscosity, changes in hemorheology, formation of coronary atherosclerotic plaque and myocardial ischemia are the basic pathological changes of CHD. This is also the embodiment of understanding of the pathological products of phlegm and blood stasis in CHD from ther perspective of TCM. Abnormal metabolism of blood lipids and the formation of atherosclerotic plaque are the manifestations of phlegm caused by abnormal metabolism of body fluids. Hemorheological changes and myocardial ischemia are the manifestations of stagnation caused by abnormal blood movement of the body. So that phlegm and blood stasis exists throughout the whole process of the disease. Although Western Medicine has a quick effect on CHD angina pectoris, the duration of effect is relatively short. Although it can improve the symptoms of phlegm and blood stasis interaction, it cannot target on the root cause. However, the combination of Traditional Chinese and Western Medicine in the treatment of CHD with phlegm and blood stasis interaction can overcome many limitations of Western Medicine alone. This study compared the effectiveness of six TCMs combined with Western Medicines in treating CHD angina pectoris by network Meta-analysis. The efficacy of different outcome indicators was ranked. The results showed that, for the overall response rate, MZXGD was the best, followed by MED and DT. For duration of angina attack, MZXGD was the best, followed by MGXBD and DT. In the improvement of hs-CRP, MZXGD was the best, followed by MXD and MED. MZXGD was the best in improving TC, followed by MED and DT. In improving TG, MED was the best, followed by MZXGD and MGXBD. MZXGD was the best in improving LDL-C, followed by MGXBD and DT. MED was the best in improving HDL-C, followed by MZXGD and MGXBD. In this study, through cluster analysis, MZXGD combined with blood-activating and stasis-removing drugs showed the best performance in simultaneously improving the overall response rate, duration of angina attack, TC, LDL-C, and hs-CRP. The results showed that the serum TC, TG, and LDL-C levels in patients with phlegm-turbidity constitution were higher than those in healthy subjects.41 It is suggested that hyperlipidemia is the material basis of blood and phlegm turbidity. Inflammatory mediators are closely related to coronary atherosclerosis. hs-CRP is a sensitive inflammatory index.42,⇓-44 Li et al 33 showed that MZXGD can effectively relieve chronic inflammatory response in patients with CHD, inhibit the progression of atherosclerosis, enhance the body’s ability to remove oxides, which is conducive to increasing plaque stability and reducing the risk of adverse cardiovascular events. Modern pharmacological study also showed that Gualou (Fructus et Semen Trichosanthis) could dilate coronary vessels, improve coronary perfusion volume, and myocardial anti-hypoxia ability.45 Xiebai (Bulbus Allii Macrostemonis) supports anti-platelet aggregation, prevents thrombosis, and inhibits atherosclerosis. Houpu (Cortex Magnoliae Officinalis) can inhibit the centrum, reduce myocardial contractility, and fight inflammation. Guizhi (Ramulus Cinnamomi) has the effects of sedation and diuresis. Since there are few Chinese patent medicines in the market for the treatment of CHD angina pectoris with phlegm and blood stasis interaction, MZXGD has great potential in the research and development of Chinese patent medicines for the treatment of CHD angina pectoris with phlegm and blood stasis interaction.

Network Meta-analysis can make up for the lack of direct comparative evidence and selection of “optimal” interventions in traditional Meta-analysis.46 In this study, indirect comparison between different TCMs was achieved through network Meta-analysis, which greatly enhanced the value of a single study by making full use of research data. However, the Meta-analysis of TCM has some limitations: there are only a few literature on individual interventions or outcome indicators included in the study, which may have publication bias; in terms of literature quality evaluation, all studies were single center and in Chinese-language. The random number table method was adopted in most random methods, but the assignment hiding and the blind method of subjects and result evaluators were not mentioned. Other sources of bias cannot be determined. None of the included studies considered the placebo effect. The above may affect the reliability of the overall research conclusions.

In conclusion, TCM with the effects of removing stasis and phlegm combined with conventional Western Medicine has obvious advantages in the treatment of CHD angina pectoris and can be used as one of the clinical options. Chinese patent medicine with phlegm and blood stasis treatment as the main curative effect needs to be further developed. It is suggested to carry out RCTs with large samples, multi-centers and high methodological quality in the future to provide more robust and reliable evidence support for clinical drug use.

5. SUPPORTING INFORMATION

Supporting data to this article can be found online at http://journaltcm.com.

REFERENCES

  • 1. Yang YJ, Hua W. . Fuwai hand book of cardiovascular medicine. Beijing: Ren Min Wei Sheng Chu Ban She 2006; 117-32. [Google Scholar]
  • 2. Liang XF. . Observation of treating 82 cases of angina pectoris with phlegm and Stasis. Shi Yong Zhong Yi Nei Ke Za Zhi 2007; 21: 73. [Google Scholar]
  • 3. Li XT. . Understanding of clinical syndrome differentiation of coronary heart disease with phlegm and blood stasis syndrome (chest obstruction and heartache). Liaoning Zhong Yi Za Zhi 2016; 43: 10-2. [Google Scholar]
  • 4. Cao HX, Zhang HM. . Interaction of phlegm and blood stasis and identification of pathogenesis of coronary heart disease. Zhong Hua Zhong Yi Yao Xue Kan 2001; 19: 544-6. [Google Scholar]
  • 5. Jia LQ, Zhang N, Song N, Zhang HY, Yang GL. . Modern biological basis on coronary heart disease (CHD) of phlegm turbidity and blood stasis syndrome from unsmoothness of vessels. Zunyi Yi Xue Yuan Xue Bao 2015; 38: 337-40. [Google Scholar]
  • 6. Chen GQ, Wu JX, Chen XL, Huang AW. . Correlation between serum homocysteine and hypersensitive C-reactive protein levels and coronary artery disease in patients with coronary heart disease. Guangdong Yi Ke Da Xue Xue Bao 2019; 3: 461-3. [Google Scholar]
  • 7. Duan XJ, Wu JR, Huang XY, et al. Comparative efficacy of Chinese herbal injections for treating acute exacerbation of chronic obstructive pulmonary disease: a Bayesian network Meta-analysis of randomized controlled trials. Evid Based Complement Alternat Med 2018; 2018: 7942936. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8. Joint task Group of international Cardiology Societies and associations and the World Health Organization on Clinical Nomenclature Standards. Nomenclature and diagnostic criteria for ischemic heart disease. Zhong Hua Xin Xue Guan Bing Za Zhi 1981; 9: 75-7. [Google Scholar]
  • 9. Ministry of Health, PRC. Guiding principles for clinical research of new Chinese medicine. Beijing: Zhong Guo Yi Yao Ke Ji Chu Ban She, 2002: 41-5. [Google Scholar]
  • 10. Discussion on treatment of angina pectoris and arrhythmia of coronary heart disease by integrated Chinese and Western Medicine. Evaluation standard of coronary heart disease angina pectoris and electrocardiogram. Zhong Guo Yao Shi 1987; 1: 71. [Google Scholar]
  • 11. Zheng XY. . Clinical research guidelines of new Chinese medicine in treating angina pectoris of coronary heart disease. Beijing: Zhong Guo Yi Yao Ke Ji Chu Ban She, 2002: 68-73. [Google Scholar]
  • 12. Higgins JP, Altman DG, Gøtzsche PC, et al. The Cochrane collaboration's tool for assessing risk of bias in randomised trials. BMJ 2011; 343: d5928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13. Bangalore S, Toklu B, Stone GW. . Meta-analysis of culprit-only versus multivessel percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction and multivessel coronary disease. Am J Cardiol 2018; 121: 529-36. [DOI] [PubMed] [Google Scholar]
  • 14. Zhang TS. . Practical evidence-based medicine methodology. Hunan: Zhong Nan Da Xue Chu Ban She, 2014: 228-37. [Google Scholar]
  • 15. Diao YJ, Sun SM, Liang N, Zhao F, Song LC, Dong J. . Effect of Wendan decoction on clinical efficacy and hs-CRP in patients with coronary heart disease complicated with phlegm-heat and blood stasis syndrome. Jilin Zhong Yi Yao 2020; 40: 193-6. [Google Scholar]
  • 16. Wang ZG, Wen XF, Zhao H. . Clinical observation of Wendan decoction and Sijunzi decoction in treating Qi deficiency and phlegm stasis syndrome of stable angina pectoris of coronary heart disease. Xin Zhong Yi 2017; 49: 20-2. [Google Scholar]
  • 17. Li FE, Qiang LX, Sun CY, Wang QX. . Liu Yujie use clinical observation of 40 cases of coronary heart disease with depression after PCI treated with Wendan decoction. Zhong Xi Yi Jie He Xin Nao Xue Guan Bing Za Zhi 2017; 15: 2766-8. [Google Scholar]
  • 18. Luo G, Ye SL. . Observation on curative effect of Huanglian Wendan decoction in treating patients with stable angina pectoris of coronary heart disease. Zhong Guo Zhong Yi Ji Zheng 2017; 26: 520-2. [Google Scholar]
  • 19. Hou BS, Li XH, Liu X, Song YQ, Zhan WY, Wang HF. . Clinical study on treatment of Angina pectoris with phlegm-heat and blood stasis type coronary heart disease by Xiaoxianxiong decoction. Henan Zhong Yi 2018; 38: 201-5. [Google Scholar]
  • 20. Guan F, Guo X. . Clinical observation on treating angina pectoris with phlegm-heat interaction after coronary stenting with Xiao xianxiong decoction. Zhong Yi Yao Dao Bao 2018; 24: 110-2. [Google Scholar]
  • 21. Ou XX, Long Y, Wang YA. . Effect of Gualou Xiebai Banxia decoction on 2D-STE and IVUS indexes in patients with phlegm turbidity syndrome of coronary heart disease. Jilin Zhong Yi Yao 2021; 41: 1600-4. [Google Scholar]
  • 22. Qiu WF, Lao JQ. . Effect of Gualou Xiebai Banxia decoction combined with atorvastatin on angina pectoris of coronary heart disease and its effect on micro-inflammatory response of patients. Hainan Yi Xue 2021; 32: 2197-200. [Google Scholar]
  • 23. Tian PP, Li J, Chen HW, Wu QJ, Zhao W, Tan YQ. . Clinical study of Gualou Xiebai Banxia decoction and Danshen decoction in the treatment of phlegm and blood stasis syndrome of unstable angina pectoris. Hainan Yi Xue Yuan Xue Bao 2021; 27: 1059-1063. [Google Scholar]
  • 24. Gong XT, Chen LM, Li ZC, He ZH. . Clinical study of Gualou Xiebai Banxia decoction combined with Shixiao San in treatment of coronary heart disease angina pectoris. Shanxi Zhong Yi 2021; 42: 886-9. [Google Scholar]
  • 25. Hu XQ. . Buyang Huanwu decoction and Gualou Xiebai Banxia decoction for coronary atherosclerotic heart disease angina pectoris treatment. Henan Zhong Yi 2020; 40: 225-8. [Google Scholar]
  • 26. Wang M, Yu XH, Zhang JQ. . Clinical study of Gualou Xiebai Banxia decoction combined with atorvastatin in the treatment of patients with phlegm and turbidity obstruction of coronary heart disease. Shi Jie Zhong Xi Yi Jie He Za Zhi 2020; 15: 147-50. [Google Scholar]
  • 27. Zhu R, Han Y, He Y. Zhang J. . Clinical study of Gualou Xiebai Banxia decoction and modified Xuefu Zhuyu decoction combined with Western Medicine in treating chest pain. Sichuan Zhong Yi 2020; 38: 95-8. [Google Scholar]
  • 28. Xu JJ, Qiu J, Zhang GH. Guo HJ. . Clinical analysis of Gualou Xiebai Banxia decoction combined with Xuefu Zhuyu decoction in treating angina pectoris of coronary heart disease. Zhong Xi Yi Jie He Xin Nao Xue Guan Bing Za Zhi 2017; 15: 2277-80. [Google Scholar]
  • 29. Dong LG, Wang FM, Mao PA, Huang FB. . Effects of Erchen decoction plus statins on blood lipid, hs-CRP, TNF-α and IL-18 in elderly patients with coronary heart disease complicated with hyperlipidemia. Zhong Guo Zhong Yi Yao Ke Ji 2021; 28: 702-4, 68. [Google Scholar]
  • 30. Hu F, Shen JF, Liu ZY. . Effects of Liujunzi decoction and Erchen decoction on Hcy, NO and hs-CRP in patients with coronary heart disease. Zhong Guo Shi Yan Fang Ji Xue Za Zhi 2020; 26: 24-9. [Google Scholar]
  • 31. Bai YM, Huang L. . Clinical effect of Erchen decoction and Xuefu Zhuyu decoction on angina pectoris of phlegm-stasis inter-junction coronary atherosclerotic heart disease. Zhong Guo Yi Yao 2019; 14: 659-63. [Google Scholar]
  • 32. Yuan QY, Gan X, Bao HG, Li ZW, Liu XX, Li L. . Effects of Zhishi Xiebai Guizhi decoction on serum inflammatory factors and vascular endothelial function in patients with unstable angina pectoris of phlegm interaction coronary heart disease. Zhong Hua Zhong Yi Yao Za Zhi 2021; 36: 6893-7. [Google Scholar]
  • 33. Li FT, Liu DD. . Clinical study of modified Zhishi Xiebai Guizhi decoction in treating stable coronary heart disease with phlegm blocking heart vessel syndrom. Henan Zhong Yi 2021; 41: 1003-6. [Google Scholar]
  • 34. Li M, Zhu H, Mei L, Liu P. . The secondary prevention effect of Zhishi Xiebaiguzhi decoction and statins on stable angina pectoris complicated with hyperlipidemia of coronary heart disease. Guangzhou Zhong Yi Yao Da Xue Xue Bao 2021; 38: 1583-7. [Google Scholar]
  • 35. Tan XD, Su W, Gao F, Lu S. . Observation on the curative effect of Zhishi Xiebai Guizhi decoction on phlegm turbidity type coronary heart disease. Sichuan Zhong Yi 2019; 37: 79-82. [Google Scholar]
  • 36. Liu Y, Shao JB, Guo LZ. . Effect of Zhishi Xiebai Guizhi decoction on coronary heart disease complicated with hyperlipidemia and its effect on endothelial function and lipid metabolism. Zhong Yao Cai 2018; 41: 476-8. [Google Scholar]
  • 37. Zhai H, Li T, Wang Y, Liu YW, Li X. . Clinical study of Danlou tablet combined with Bisoprolol in treating angina pectoris of coronary heart disease. Zhong Hua Zhong Yi Yao Xue Kan 2019; 34: 341-5. [Google Scholar]
  • 38. Yang K. . Clinical observation of Danlou tablet combined with aspirin in treating elder people angina pectoris of coronary heart disease. Zhong Hua Zhong Yi Yao Xue Kan 2019; 37: 369-71. [Google Scholar]
  • 39. Zhang JH, Zhao ZH, Li HX, Yan SY. . Effect of Danlou tablet on blood lipid and hemorheology in patients with coronary heart disease complicated with hyperlipidemia. Zhong Xi Yi Jie He Xin Nao Xue Guan Bing Za Zhi 2018; 16: 1319-23. [Google Scholar]
  • 40. Chen JF, Lei ZY, Liu CF, et al. Effect of Danlou tablet on phlegm-stasis syndrome of coronary heart disease and its effect on serum inflammatory factors. Zhong Xi Yi Jie He Xin Nao Xue Guan Bing Za Zhi 2018; 16: 3401-4. [Google Scholar]
  • 41. Yuan ZK, Huang XP, Wang LP, Wang P, Wang DS. . Clinical study on the characteristics of phlegm stasis syndrome in coronary heart disease. Yunnan Zhong Yi Xue Yuan Xue Bao 2011; 34: 3-7. [Google Scholar]
  • 42. Yao CL, Li Y, Lu XJ, Jiang XJ. . Relationship between super-oxide dismutase, its isoenzyme and hypersensitive C-reactive protein and coronary heart disease. Xian Dai Jian Yan Yi Xue Za Zhi 2016; 31: 73-5. [Google Scholar]
  • 43. Lu Y, Peng JJ. . Clinical significance of serum SOD detection in patients with coronary heart disease. Henan Da Xue Xue Bao 2019; 38: 201-3. [Google Scholar]
  • 44. Zhang Z, Chen A, Yu T, et al. Exploring the pharmacological mechanism of Danhe granules against hyperlipidemia by means of network pharmacology and verified by preliminary experiments. World J Tradit Chin Med 2021; 7: 436-44. [Google Scholar]
  • 45. Zhang X, Li X, Zhou GF, et al. Research of molecular mechanism of Zhishi Xiebai Guizhi decoction on coronary heart disease treatment based on network pharmacology. Hunan Zhong Yi Yao Da Xue Xue Bao 2020; 40: 571-7. [Google Scholar]
  • 46. Wang XL, Qin ZJ, Lu YH. . Application of Stata software in network Meta-analysis. Xian Dai Yu Fang Yi Xue 2016; 43: 3461-4. [Google Scholar]

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