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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Pharmacol.</journal-id>
<journal-title>Frontiers in Pharmacology</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Pharmacol.</abbrev-journal-title>
<issn pub-type="epub">1663-9812</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
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<article-meta>
<article-id pub-id-type="publisher-id">1375795</article-id>
<article-id pub-id-type="doi">10.3389/fphar.2024.1375795</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Pharmacology</subject>
<subj-group>
<subject>Systematic Review</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Effects of modified Danggui Sini Decoction as adjuvant therapy for angina pectoris in coronary heart disease: a systematic review and meta-analysis based on randomised controlled trials</article-title>
<alt-title alt-title-type="left-running-head">Wang et al.</alt-title>
<alt-title alt-title-type="right-running-head">
<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3389/fphar.2024.1375795">10.3389/fphar.2024.1375795</ext-link>
</alt-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Wang</surname>
<given-names>He</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="fn" rid="fn1">
<sup>&#x2020;</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/2639113/overview"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
<role content-type="https://credit.niso.org/contributor-roles/Writing - review &#x26; editing/"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Liu</surname>
<given-names>Changxing</given-names>
</name>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
<role content-type="https://credit.niso.org/contributor-roles/Writing - review &#x26; editing/"/>
<xref ref-type="aff" rid="aff3">
<sup>2</sup>
</xref>
<xref ref-type="fn" rid="fn1">
<sup>&#x2020;</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Guo</surname>
<given-names>Xinyi</given-names>
</name>
<xref ref-type="aff" rid="aff3">
<sup>3</sup>
</xref>
<xref ref-type="fn" rid="fn1">
<sup>&#x2020;</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/1959178/overview"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
<role content-type="https://credit.niso.org/contributor-roles/Writing - review &#x26; editing/"/>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Yang</surname>
<given-names>Jianfei</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="corresp" rid="c001">&#x2a;</xref>
<role content-type="https://credit.niso.org/contributor-roles/funding-acquisition/"/>
<role content-type="https://credit.niso.org/contributor-roles/supervision/"/>
<role content-type="https://credit.niso.org/contributor-roles/validation/"/>
<role content-type="https://credit.niso.org/contributor-roles/Writing - review &#x26; editing/"/>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Zhou</surname>
<given-names>Yabin</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="corresp" rid="c001">&#x2a;</xref>
<role content-type="https://credit.niso.org/contributor-roles/funding-acquisition/"/>
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<aff id="aff1">
<sup>1</sup>
<institution>The First Hospital of Heilongjiang University of Chinese Medicine</institution>, <addr-line>Harbin</addr-line>, <country>China</country>
</aff>
<aff id="aff2">
<sup>2</sup>
<institution>First Clinical College of Medicine, Heilongjiang University of Chinese Medicine</institution>, <addr-line>Harbin</addr-line>, <country>China</country>
</aff>
<aff id="aff3">
<sup>3</sup>
<institution>Clinical College of Medicine, Chengdu University of Traditional Chinese Medicine</institution>, <addr-line>Chengdu</addr-line>, <country>China</country>
</aff>
<author-notes>
<fn fn-type="edited-by">
<p>
<bold>Edited by:</bold> <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/15167/overview">Michael Heinrich</ext-link>, University College London, United Kingdom</p>
</fn>
<fn fn-type="edited-by">
<p>
<bold>Reviewed by:</bold> <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/1010190/overview">Lin Zhu</ext-link>, The Chinese University of Hong Kong, China</p>
<p>
<ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/434642/overview">Tao Yi</ext-link>, Hong Kong Baptist University, Hong Kong SAR, China</p>
<p>
<ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/1114390/overview">Chunxiang Liu</ext-link>, Tianjin University of Traditional Chinese Medicine, China</p>
</fn>
<corresp id="c001">&#x2a;Correspondence: Yabin Zhou, <email>yabzhou@163.com</email>; Jianfei Yang, <email>yangjianfei119@163.com</email>
</corresp>
<fn id="fn1" fn-type="equal">
<label>
<sup>&#x2020;</sup>
</label>
<p>These authors have contributed equally to this work and share first authorship</p>
</fn>
</author-notes>
<pub-date pub-type="epub">
<day>04</day>
<month>06</month>
<year>2024</year>
</pub-date>
<pub-date pub-type="collection">
<year>2024</year>
</pub-date>
<volume>15</volume>
<elocation-id>1375795</elocation-id>
<history>
<date date-type="received">
<day>24</day>
<month>01</month>
<year>2024</year>
</date>
<date date-type="accepted">
<day>09</day>
<month>05</month>
<year>2024</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#xa9; 2024 Wang, Liu, Guo, Yang and Zhou.</copyright-statement>
<copyright-year>2024</copyright-year>
<copyright-holder>Wang, Liu, Guo, Yang and Zhou</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p>
</license>
</permissions>
<abstract>
<sec>
<title>Introduction</title>
<p>This systematic review evaluates the efficacy of the Chinese herbal formula modified Danggui Sini Decoction as an adjunctive treatment for angina pectoris in patients with coronary heart disease.</p>
</sec>
<sec>
<title>Methods</title>
<p>We conducted a comprehensive search for randomized controlled trials that investigated the effects of modified Danggui Sini Decoction in combination with conventional Western medication on angina pectoris in coronary artery disease, published up to July 2023 across eight databases, including China Knowledge International Literature screening and data extraction were performed by two researchers following predefined inclusion and exclusion criteria. The quality of included studies was assessed using the Cochrane Handbook version 5.1, and meta-analysis was executed via RevMan 5.4 software.</p>
</sec>
<sec>
<title>Results</title>
<p>Thirteen studies encompassing 1,232 participants were incorporated. The meta-analysis revealed that combining modified Danggui Sini Decoction with conventional Western medication significantly enhanced overall clinical efficacy, reduced the duration of angina attacks, decreased the Chinese medicine syndrome score, improved inflammatory markers and cardiac function, lowered serum NT-proBNP levels, and elevated the Seattle Angina Questionnaire scores compared to the control group.</p>
</sec>
<sec>
<title>Conclusion</title>
<p>Modified Danggui Sini Decoction, when used alongside conventional Western medications, shows promise in treating coronary artery disease patients with angina pectoris and may serve as a beneficial adjunctive therapy in clinical settings. Nonetheless, due to the limited quantity and quality of the included studies, further high-caliber research is essential to substantiate these findings.</p>
</sec>
<sec>
<title>Systematic Review Registration</title>
<p> https://inplasy.com/? s&#x003D;202390078, identifier INPLASY 202390078.</p>
</sec>
</abstract>
<kwd-group>
<kwd>modify Danggui Sini Decoction</kwd>
<kwd>conventional western medicine</kwd>
<kwd>angina pectoris</kwd>
<kwd>meta-analysis</kwd>
<kwd>systematic review</kwd>
</kwd-group>
<custom-meta-wrap>
<custom-meta>
<meta-name>section-at-acceptance</meta-name>
<meta-value>Ethnopharmacology</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<sec id="s1">
<title>1 Introduction</title>
<p>Coronary arteriosclerotic heart disease, also known as coronary heart disease (CHD), is a cardiac condition caused by atherosclerotic lesions in the coronary arteries. This leads to narrowing and blockage of the vessel lumen, resulting in myocardial ischemia or necrosis (<xref ref-type="bibr" rid="B11">Guo Z. et al., 2023</xref>). Angina pectoris, characterized by transient myocardial ischemia and chest pain, is the most common clinical manifestation of CHD and can progress to acute myocardial infarction with a high mortality rate (<xref ref-type="bibr" rid="B32">Wang and Chen, 2018</xref>). A global burden of disease study in 2017 reported 126.45 million cases of ischemic heart disease worldwide, including 10.6365 million new cases, leading to 8.9304 million deaths and making it the leading cause of mortality globally (<xref ref-type="bibr" rid="B7">Dalys and Collaborators, 2018</xref>; <xref ref-type="bibr" rid="B9">GBD Causes of Death Collaborators, 2018</xref>). Further research has indicated that the ratio of years lived with disability (YLD) to years of life lost (YLL) due to CHD in China is 14.2:1, with the burden of CHD ranking second and an absolute value increase of 122.0% (<xref ref-type="bibr" rid="B3">China Cardiovascular Health and Disease Report, 2021 Coronary Heart Disease Section, 2022</xref>; <xref ref-type="bibr" rid="B28">Buyiman et al., 2023</xref>). Consequently, there is a pressing need to develop early, safe, and cost-efficient interventions to improve patient daily functioning, enhance their quality of life, and alleviate the economic burden on individuals and society.</p>
<p>Currently, the treatment goals for CHD aim to reduce the frequency and severity of angina attacks, and prevent cardiovascular events such as acute myocardial infarction (AMI), sudden cardiac death, and heart failure (<xref ref-type="bibr" rid="B34">Xiaoping and Zhao, 2023</xref>). Antiplatelet aggregating drugs are commonly used in Western medicine, with severe cases possibly requiring percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) (<xref ref-type="bibr" rid="B39">Yassen et al., 2023</xref>). However, despite significant improvements from interventional therapies and conventional Western medicine, the long-term efficacy in improving survival rates and decreasing recurrence rates of CHD remains unclear, with considerable side effects (<xref ref-type="bibr" rid="B10">Guo J. et al., 2023</xref>). CHD not only threatens the health and life of patients but also imposes a significant economic burden on society and families. Among cardiovascular diseases, the recurrence rate of coronary angina is notably high, severely affecting patients&#x2019; normal life and work (<xref ref-type="bibr" rid="B17">Jia-Yi and Xi-Ping, 2023</xref>). Therefore, an increasing number of researchers are turning their focus to complementary and alternative medicine.</p>
<p>In traditional Chinese medicine (TCM), CHD and angina pectoris are categorized under &#x201c;chest impediment&#x201d; and &#x201c;heartache.&#x201d; The etiology of these conditions is attributed to deficiencies in Qi, blood, Yin, and Yang as underlying factors, complemented by Qi and blood stasis, cold coagulation in the blood vessels, and phlegm obstruction as primary manifestations (<xref ref-type="bibr" rid="B21">Liu et al., 2023</xref>). The modified Danggui Sini Decoction, derived from the &#x201c;Shang Han Lun,&#x201d; is reputed to nourish and activate blood, warm meridians, and disperse cold. Recently, this decoction has demonstrated promising clinical outcomes in treating CHD (<xref ref-type="bibr" rid="B45">Zhang and Wang, 2017</xref>; <xref ref-type="bibr" rid="B23">Lu et al., 2019</xref>; <xref ref-type="bibr" rid="B48">Zifeng, 2019</xref>; <xref ref-type="bibr" rid="B1">Chen et al., 2020</xref>; <xref ref-type="bibr" rid="B15">Jia, 2020</xref>; <xref ref-type="bibr" rid="B25">Qi-Min, 2020</xref>; <xref ref-type="bibr" rid="B44">Zhang, 2020</xref>; <xref ref-type="bibr" rid="B6">Cui et al., 2021</xref>; <xref ref-type="bibr" rid="B30">Wang, 2021</xref>; <xref ref-type="bibr" rid="B33">Wang et al., 2021</xref>; <xref ref-type="bibr" rid="B12">Du et al., 2022</xref>; <xref ref-type="bibr" rid="B20">Li, 2022</xref>; <xref ref-type="bibr" rid="B14">Hui and Qian, 2023</xref>). However, the research conducted to date predominantly features small sample sizes and single-center clinical trials, highlighting a lack of comprehensive, high-quality systematic reviews. Consequently, this study utilizes an evidence-based medicine approach to systematically assess the efficacy of the modified Danggui Sini Decoction alongside conventional Western medicine in treating CHD and angina pectoris, aiming to provide objective, evidence-based recommendations for clinical treatment and drug guidance.</p>
</sec>
<sec id="s2" sec-type="methods">
<title>2 Methods</title>
<p>This systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement (as detailed in <xref ref-type="sec" rid="s11">Supplementary Material</xref> S1). Additionally, this review was registered with PROSPERO (registration number INPLASY202390078).</p>
<sec id="s2-1">
<title>2.1 Literature search</title>
<p>Search terms in Chinese for the modified Danggui Sini Decoction included &#x201c;Danggui Sini Tang,&#x201d; &#x201c;Coronary atherosclerosis,&#x201d; &#x201c;Coronary heart disease,&#x201d; &#x201c;Coronary atherosclerotic heart disease,&#x201d; &#x201c;Angina pectoris,&#x201d; and &#x201c;Myocardial ischaemia.&#x201d; English search terms comprised &#x201c;modified Danggui Sini Decoction,&#x201d; &#x201c;Coronary atherosclerosis,&#x201d; &#x201c;Coronary heart disease,&#x201d; &#x201c;Myocardial ischemia,&#x201d; and &#x201c;Angina pectoris.&#x201d; These terms were utilized in databases such as the China Knowledge Information Network (CNKI), WanFang Database, VIP Database, Chinese Biomedical Literature Database (CBM), PubMed, Embase, Web of Science. Searches were conducted by title, keywords, subject terms, and free word combinations. The search period extended from the inception of each database up to July 2023. Refer to the supplementary document for a detailed search strategy (<xref ref-type="sec" rid="s11">Supplementary Table S1</xref>).</p>
</sec>
<sec id="s2-2">
<title>2.2 Inclusion criteria</title>
<sec id="s2-2-1">
<title>2.2.1 Literature type</title>
<p>Included were publicly published RCTs both within China and internationally, in both Chinese and English, with no requirement for blinding.</p>
</sec>
<sec id="s2-2-2">
<title>2.2.2 Study subjects</title>
<p>The diagnostic criteria for UA were based on the Guidelines for the Diagnosis and Treatment of Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction, and the Guidelines for the Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndromes (2016 Edition) (<xref ref-type="bibr" rid="B19">Lei, 2012</xref>; <xref ref-type="bibr" rid="B5">Chinese Medical Association and Division of Cardiovascular Diseases, 2017</xref>). Similarly, the diagnosis of Stable Angina (SA) adhered to criteria set forth in the Guidelines for the Diagnosis and Treatment of Chronic Stable Angina (<xref ref-type="bibr" rid="B4">Chinese Medical Association Cardiovascular Disease Branch and Chinese Journal of Cardiovascular Disease Editorial Committee, 2007</xref>).</p>
</sec>
<sec id="s2-2-3">
<title>2.2.3 Intervention measures</title>
<p>The control group received conventional Western medicines, while the experimental group was treated with modified Danggui Sini Decoction in addition to the standard treatment.</p>
</sec>
<sec id="s2-2-4">
<title>2.2.4 Outcome measures</title>
<p>The primary efficacy outcomes encompassed the clinical effective rate (including angina pectoris effective rate, electrocardiogram effective rate, nitroglycerin dosage reduction rate, and traditional Chinese medicine syndrome effective rate). Secondary outcomes entailed the traditional Chinese medicine syndrome score [as specified in the &#x201c;Guidelines for Clinical Research of New Chinese Medicines&#x201d; (<xref ref-type="bibr" rid="B46">Zheng, 2002</xref>)], cardiac function indicators [cardiac output (CO), left ventricular ejection fraction (LVEF), and left ventricular end-diastolic diameter (LVEDD)], angina pectoris episodes (frequency and duration of angina attacks), Seattle Angina Questionnaire (SAQ) score, and inflammatory factors [interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-&#x3b1;), and high-sensitivity C-reactive protein (hs-CRP)].</p>
</sec>
</sec>
<sec id="s2-3">
<title>2.3 Exclusion criteria</title>
<p>Exclusions included duplicate publications, reviews, conference papers, animal studies, case reports, studies with incomplete data or lacking outcome indicators, and studies whose interventions did not align with the inclusion criteria.</p>
</sec>
<sec id="s2-4">
<title>2.4 Literature screening and data extraction</title>
<p>Two researchers independently conducted literature screening and data extraction based on the inclusion and exclusion criteria. Discrepancies were resolved through discussion or consultation with a third researcher. Extracted data covered authors, publication year, title, sample sizes of test and control groups, demographics (sex, age, disease duration), interventions, treatment duration, and outcome measures.</p>
</sec>
<sec id="s2-5">
<title>2.5 Quality assessment of included literature</title>
<p>Quality was assessed using the Cochrane Handbook 5.1 &#x201c;Risk of Bias Assessment&#x201d; tool, examining six dimensions: random sequence generation, allocation concealment, blinding implementation, data completeness, selective reporting, and other sources of bias. Outcomes were categorized as &#x201c;low risk,&#x201d; &#x201c;high risk,&#x201d; or &#x201c;unclear risk&#x201d; of bias.</p>
</sec>
<sec id="s2-6">
<title>2.6 Evidence quality evaluation</title>
<p>Use GRADEprofiler 3.6 for evidence quality evaluation, divided into four levels: high (A), medium (B), low (C), and extremely low (D). Whether to downgrade during the evaluation process mainly considers five aspects: research limitations, inconsistency, indirectness, imprecision, and publication bias.</p>
</sec>
<sec id="s2-7">
<title>2.7 Statistical methods</title>
<p>Meta-analysis was conducted using RevMan 5.4 software. For count data, odds ratios (OR) or risk ratios (RR) were used, while mean difference (MD) or standardized mean difference (SMD) were employed for continuous data, with 95% confidence intervals (CI) calculated. Heterogeneity was assessed by the <italic>I</italic>
<sup>2</sup> statistic; a fixed-effects model was applied if <italic>p</italic> &#x003e; 0.10 and <italic>I</italic>
<sup>2</sup> &#x2264; 50%, and a random-effects model for <italic>p</italic> &#x2264; 0.10 and <italic>I</italic>
<sup>2</sup> &#x003e; 50%, with subgroup or sensitivity analysis as appropriate. Publication bias was evaluated with a funnel plot for studies including more than 10 outcome measures.</p>
</sec>
</sec>
<sec id="s3" sec-type="results">
<title>3 Results</title>
<sec id="s3-1">
<title>3.1 Results of literature screening</title>
<p>A total of 432 pieces of literature were retrieved. After removing duplicates using Endnote software, 219 remained and were assessed according to the inclusion and exclusion criteria, ultimately including 13 studies (<xref ref-type="bibr" rid="B45">Zhang and Wang, 2017</xref>; <xref ref-type="bibr" rid="B23">Lu et al., 2019</xref>; <xref ref-type="bibr" rid="B48">Zifeng, 2019</xref>; <xref ref-type="bibr" rid="B1">Chen et al., 2020</xref>; <xref ref-type="bibr" rid="B15">Jia, 2020</xref>; <xref ref-type="bibr" rid="B25">Qi-Min, 2020</xref>; <xref ref-type="bibr" rid="B44">Zhang, 2020</xref>; <xref ref-type="bibr" rid="B6">Cui et al., 2021</xref>; <xref ref-type="bibr" rid="B30">Wang, 2021</xref>; <xref ref-type="bibr" rid="B33">Wang et al., 2021</xref>; <xref ref-type="bibr" rid="B12">Du et al., 2022</xref>; <xref ref-type="bibr" rid="B20">Li, 2022</xref>; <xref ref-type="bibr" rid="B14">Hui and Qian, 2023</xref>). The literature screening process is depicted in <xref ref-type="fig" rid="F1">Figure 1</xref>. In accordance with the &#x201c;Type A extract&#x201d; definition from the ConPhyMP consensus statement (<xref ref-type="bibr" rid="B24">Peng et al., 2023</xref>), a summary table was compiled to describe the botanical drug components reported in the original studies. As a Type A extract, modified Danggui Sini Decoction comprises six botanical drugs, aimed at warming meridians, dispelling cold, nourishing blood, and unblocking meridians. The core prescription in all studies was modified Danggui Sini Decoction, with additional botanical drugs like Angelica sinensis (Oliv.) Diels (Umbelliferae; <italic>Angelicae sinensis</italic> Radix) (Danggui), <italic>Asarum heterotropoides</italic> F. Schmidt (Aristolochiaceae Juss.) (Xixin), <italic>Cynanchum otophyllum</italic> Schneid. (Contortae.) (Baishao), <italic>Glycyrrhiza uralensis</italic> Fisch. (Fabaceae Lindl.) (Gancao), <italic>Cinnamomum cassia</italic> (L.) D. (DonRamulus Cinnamomi) (Guizhi), <italic>Tetrapanax papyrifer</italic> (Hook.) K. Koch (<italic>Tetrapanax papyriferus</italic>) (Tongcao), adjusted according to syndrome differentiation. The composition of these prescriptions is detailed in <xref ref-type="sec" rid="s11">Supplementary Table S2</xref>.</p>
<fig id="F1" position="float">
<label>FIGURE 1</label>
<caption>
<p>Literature screening process.</p>
</caption>
<graphic xlink:href="fphar-15-1375795-g001.tif"/>
</fig>
</sec>
<sec id="s3-2">
<title>3.2 Basic information of included studies</title>
<p>The review included 13 RCTs, encompassing 1,232 patients&#x2014;616 in the treatment group and 616 in the control group. Baseline characteristics across studies were comparable, with detailed features presented in <xref ref-type="table" rid="T1">Table 1</xref>.</p>
<table-wrap id="T1" position="float">
<label>TABLE 1</label>
<caption>
<p>Basic characteristics of the included studies.</p>
</caption>
<table>
<thead valign="top">
<tr>
<th align="center" rowspan="2">Subjects</th>
<th align="center" rowspan="2">Disease type</th>
<th align="center" colspan="2">Sample size (m/f)</th>
<th align="center" colspan="2">Average age/years</th>
<th align="center" colspan="2">Interventions</th>
<th align="center" colspan="2">Average duration of illness/year</th>
<th align="center" rowspan="2">Treatment/week</th>
<th align="center" rowspan="2">Outcomes</th>
</tr>
<tr>
<th align="center">T</th>
<th align="center">C</th>
<th align="center">T</th>
<th align="center">C</th>
<th align="center">T</th>
<th align="center">C</th>
<th align="center">T</th>
<th align="center">C</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td align="center">
<xref ref-type="bibr" rid="B14">Hui and Qian (2023)</xref>
</td>
<td align="center">UA</td>
<td align="center">40(23/17)</td>
<td align="center">40(21/19)</td>
<td align="center">62.17 &#xb1; 3.24</td>
<td align="center">61.33 &#xb1; 2.97</td>
<td align="center">modified Danggui Sini Decoction&#x002B;C</td>
<td align="center">CWM</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">4</td>
<td align="center">&#x2460;&#x2464;&#x2465;</td>
</tr>
<tr>
<td align="center">
<xref ref-type="bibr" rid="B20">Li (2022)</xref>
</td>
<td align="center">SA</td>
<td align="center">55(30/25)</td>
<td align="center">55(32/23)</td>
<td align="center">67.30 &#xb1; 5.71</td>
<td align="center">68.37 &#xb1; 7.20</td>
<td align="center">modified Danggui Sini Decoction&#x002B;C</td>
<td align="center">CWM</td>
<td align="center">2.56 &#xb1; 0.58</td>
<td align="center">2.67 &#xb1; 0.63</td>
<td align="center">12</td>
<td align="center">&#x2460;&#x2464;&#x2466;</td>
</tr>
<tr>
<td align="center">
<xref ref-type="bibr" rid="B12">Du et al., 2022</xref>
</td>
<td align="center">SA/UA</td>
<td align="center">39(24/15)</td>
<td align="center">39(27/12)</td>
<td align="center">64.87 &#xb1; 6.51</td>
<td align="center">65.81 &#xb1; 6.24</td>
<td align="center">modified Danggui Sini Decoction&#x002B;C</td>
<td align="center">CWM</td>
<td align="center">6.14 &#xb1; 2.03</td>
<td align="center">6.38 &#xb1; 1.53</td>
<td align="center">4</td>
<td align="center">&#x2461;&#x2462;&#x2463;&#x2464;&#x2467;</td>
</tr>
<tr>
<td align="center">
<xref ref-type="bibr" rid="B6">Cui et al. (2021)</xref>
</td>
<td align="center">UA</td>
<td align="center">34(13/21)</td>
<td align="center">34(11/24)</td>
<td align="center">55.24 &#xb1; 2.21</td>
<td align="center">53.03 &#xb1; 1.41</td>
<td align="center">modified Danggui Sini Decoction&#x002B;C</td>
<td align="center">CWM</td>
<td align="center">4.97 &#xb1; 0.21</td>
<td align="center">4.93 &#xb1; 0.26</td>
<td align="center">3</td>
<td align="center">&#x2460;&#x2464;&#x2466;</td>
</tr>
<tr>
<td align="center">
<xref ref-type="bibr" rid="B30">Wang (2021)</xref>
</td>
<td align="center">SA</td>
<td align="center">45(26/19)</td>
<td align="center">45(24/21)</td>
<td align="center">70.16 &#xb1; 2.32</td>
<td align="center">70.23 &#xb1; 2.83</td>
<td align="center">modified Danggui Sini Decoction&#x002B;C</td>
<td align="center">CWM</td>
<td align="center">5.47 &#xb1; 1.31</td>
<td align="center">5.52 &#xb1; 1.28</td>
<td align="center">4</td>
<td align="center">&#x2460;&#x2464;&#x2465;&#x2466;</td>
</tr>
<tr>
<td align="center">
<xref ref-type="bibr" rid="B33">Wang et al. (2021)</xref>
</td>
<td align="center">SA/UA</td>
<td align="center">132 (64/68)</td>
<td align="center">132(66/66)</td>
<td align="center">67.61 &#xb1; 7.81</td>
<td align="center">66.13 &#xb1; 6.92</td>
<td align="center">modified Danggui Sini Decoction&#x002B;C</td>
<td align="center">CWM</td>
<td align="center">8.15 &#xb1; 0.94</td>
<td align="center">8.94 &#xb1; 1.12</td>
<td align="center">4</td>
<td align="center">&#x2463;&#x2464;&#x2465;</td>
</tr>
<tr>
<td align="center">
<xref ref-type="bibr" rid="B15">Jia (2020)</xref>
</td>
<td align="center">UA</td>
<td align="center">30(17/13)</td>
<td align="center">30(15/15)</td>
<td align="center">60.23 &#xb1; 15.32</td>
<td align="center">61.07 &#xb1; 14.8</td>
<td align="center">modified Danggui Sini Decoction&#x002B;C</td>
<td align="center">CWM</td>
<td align="center">3.01 &#xb1; 3.71</td>
<td align="center">3.25 &#xb1; 4.2</td>
<td align="center">4</td>
<td align="center">&#x2460;&#x2461;&#x2462;&#x2463;</td>
</tr>
<tr>
<td align="center">
<xref ref-type="bibr" rid="B25">Qi-Min (2020)</xref>
</td>
<td align="center">SA</td>
<td align="center">36(20/16)</td>
<td align="center">36(19/17)</td>
<td align="center">56.23 &#xb1; 15.32</td>
<td align="center">58.07 &#xb1; 14.8</td>
<td align="center">modified Danggui Sini Decoction&#x002B;C</td>
<td align="center">CWM</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">8</td>
<td align="center">&#x2460;&#x2461;&#x2462;&#x2463;&#x2464;&#x2466;</td>
</tr>
<tr>
<td align="center">
<xref ref-type="bibr" rid="B44">Zhang (2020)</xref>
</td>
<td align="center">SA/UA</td>
<td align="center">48(22/26)</td>
<td align="center">48(25/23)</td>
<td align="center">79.68 &#xb1; 9.32</td>
<td align="center">78.07 &#xb1; 9.8</td>
<td align="center">modified Danggui Sini Decoction&#x002B;C</td>
<td align="center">CWM</td>
<td align="center">6.29 &#xb1; 2.71</td>
<td align="center">6.04 &#xb1; 2.42</td>
<td align="center">4</td>
<td align="center">&#x2460;&#x2468;&#x2469;</td>
</tr>
<tr>
<td align="center">
<xref ref-type="bibr" rid="B1">Chen et al. (2020)</xref>
</td>
<td align="center">UA</td>
<td align="center">30(15/15)</td>
<td align="center">30(18/12)</td>
<td align="center">56.2 &#xb1; 3.6</td>
<td align="center">57.4 &#xb1; 4.8</td>
<td align="center">modified Danggui Sini Decoction&#x002B;C</td>
<td align="center">CWM</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">4</td>
<td align="center">&#x2460;&#x2464;&#x2465;&#x2468;</td>
</tr>
<tr>
<td align="center">
<xref ref-type="bibr" rid="B48">Zifeng (2019)</xref>
</td>
<td align="center">SA</td>
<td align="center">30(12/18)</td>
<td align="center">30(16/14)</td>
<td align="center">63.23 &#xb1; 5.32</td>
<td align="center">64.07 &#xb1; 4.8</td>
<td align="center">modified Danggui Sini Decoction&#x002B;C</td>
<td align="center">CWM</td>
<td align="center">5.3 &#xb1; .8</td>
<td align="center">5.1 &#xb1; 2.7</td>
<td align="center">6</td>
<td align="center">&#x2461;&#x2462;&#x2463;&#x2466;&#x2469;</td>
</tr>
<tr>
<td align="center">
<xref ref-type="bibr" rid="B23">Lu et al. (2019)</xref>
</td>
<td align="center">SA</td>
<td align="center">57(31/26)</td>
<td align="center">57(29/28)</td>
<td align="center">72.16 &#xb1; 7.21</td>
<td align="center">73.07 &#xb1; 8.02</td>
<td align="center">modified Danggui Sini Decoction&#x002B;C</td>
<td align="center">CWM</td>
<td align="center">10.11 &#xb1; 2.71</td>
<td align="center">9.89 &#xb1; 1.94</td>
<td align="center">4</td>
<td align="center">&#x2461;&#x2462;&#x2463;&#x2464;&#x2465;&#x2467;</td>
</tr>
<tr>
<td align="center">
<xref ref-type="bibr" rid="B45">Zhang and Wang (2017)</xref>
</td>
<td align="center">SA/UA</td>
<td align="center">40(27/13)</td>
<td align="center">40(15/25)</td>
<td align="center">65.23 &#xb1; 7.76</td>
<td align="center">65.15 &#xb1; 7.95</td>
<td align="center">modified Danggui Sini Decoction&#x002B;C</td>
<td align="center">CWM</td>
<td align="center">2.79 &#xb1; 1.71</td>
<td align="center">3.25 &#xb1; 1.20</td>
<td align="center">12</td>
<td align="center">&#x2463;&#x2464;&#x2467;</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn>
<p>Note: T, trial group; C, control group; &#x2212;, Not reported; SA, stable angina; UA, unstable angina; CWM, conventional western medicine (including antiplatelet agents, statin lipid-lowering drugs, &#x3b2;-blockers, nitrates, etc.); &#x2460;Angina pectoris effective rate; &#x2461;Ecg response rate; &#x2462;Nitroglycerin reduction and discontinuation rate; &#x2463;TCM, symptom Effective rate; &#x2464;Episodes of angina pectoris (Number of angina attacks, Duration of angina pectoris); &#x2465;Cardiac function index (CO, LVEF, LVEDD); &#x2466;TCM, syndrome score; &#x2467;SAQ, score; &#x2468;NT-ProBNP; &#x2469;Inflammatory factors.</p>
</fn>
</table-wrap-foot>
</table-wrap>
</sec>
<sec id="s3-3">
<title>3.3 Quality assessment of included studies</title>
<p>The quality of the studies was assessed using the Cochrane Handbook 5.1 &#x201c;Risk of Bias Assessment&#x201d; tool. Ten studies (<xref ref-type="bibr" rid="B23">Lu et al., 2019</xref>; <xref ref-type="bibr" rid="B1">Chen et al., 2020</xref>; <xref ref-type="bibr" rid="B15">Jia, 2020</xref>; <xref ref-type="bibr" rid="B25">Qi-Min, 2020</xref>; <xref ref-type="bibr" rid="B6">Cui et al., 2021</xref>; <xref ref-type="bibr" rid="B30">Wang, 2021</xref>; <xref ref-type="bibr" rid="B33">Wang et al., 2021</xref>; <xref ref-type="bibr" rid="B12">Du et al., 2022</xref>; <xref ref-type="bibr" rid="B20">Li, 2022</xref>; <xref ref-type="bibr" rid="B14">Hui and Qian, 2023</xref>) utilized the randomized numeric table method for randomization. Three studies (<xref ref-type="bibr" rid="B45">Zhang and Wang, 2017</xref>; <xref ref-type="bibr" rid="B48">Zifeng, 2019</xref>; <xref ref-type="bibr" rid="B44">Zhang, 2020</xref>) did not clearly specify their randomization techniques; none disclosed details on allocation concealment or blinding, hence were considered at unknown risk. All studies reported complete outcomes, with no evidence of selective outcome reporting or other biases, classifying them at low risk (<xref ref-type="fig" rid="F2">Figures 2</xref>, <xref ref-type="fig" rid="F3">3</xref>).</p>
<fig id="F2" position="float">
<label>FIGURE 2</label>
<caption>
<p>Summary of the risk of bias in the included literature.</p>
</caption>
<graphic xlink:href="fphar-15-1375795-g002.tif"/>
</fig>
<fig id="F3" position="float">
<label>FIGURE 3</label>
<caption>
<p>Risk of bias proportional to the risk of inclusion in the literature.</p>
</caption>
<graphic xlink:href="fphar-15-1375795-g003.tif"/>
</fig>
</sec>
<sec id="s3-4">
<title>3.4 Meta-analysis results</title>
<sec id="s3-4-1">
<title>3.4.1 Efficacy in angina pectoris</title>
<p>Eight studies (<xref ref-type="bibr" rid="B1">Chen et al., 2020</xref>; <xref ref-type="bibr" rid="B15">Jia, 2020</xref>; <xref ref-type="bibr" rid="B25">Qi-Min, 2020</xref>; <xref ref-type="bibr" rid="B44">Zhang, 2020</xref>; <xref ref-type="bibr" rid="B6">Cui et al., 2021</xref>; <xref ref-type="bibr" rid="B30">Wang, 2021</xref>; <xref ref-type="bibr" rid="B20">Li, 2022</xref>; <xref ref-type="bibr" rid="B14">Hui and Qian, 2023</xref>) involving 636 patients assessed the efficacy of treatment for angina pectoris. These studies demonstrated homogeneity (<italic>p</italic> &#x003D; 0.99, <italic>I</italic>
<sup>2</sup> &#x003D; 0), and a fixed-effects model was applied for the meta-analysis. The results indicated that the experimental group experienced a significant improvement in the treatment efficacy of angina pectoris compared to the control group, with a statistically significant difference [RR &#x003D; 1.23, 95% CI (1.14, 1.33), <italic>p</italic> &#x003c; 0.00001] (<xref ref-type="fig" rid="F4">Figure 4</xref>).</p>
<fig id="F4" position="float">
<label>FIGURE 4</label>
<caption>
<p>Meta-analysis of the effective rate of angina pectoris in patients with coronary heart disease angina pectoris treated with modified Danggui Sini Decoction in combination with conventional western drugs.</p>
</caption>
<graphic xlink:href="fphar-15-1375795-g004.tif"/>
</fig>
</sec>
<sec id="s3-4-2">
<title>3.4.2 Effective rate of TCM symptoms</title>
<p>Seven studies (<xref ref-type="bibr" rid="B45">Zhang and Wang, 2017</xref>; <xref ref-type="bibr" rid="B23">Lu et al., 2019</xref>; <xref ref-type="bibr" rid="B48">Zifeng, 2019</xref>; <xref ref-type="bibr" rid="B15">Jia, 2020</xref>; <xref ref-type="bibr" rid="B25">Qi-Min, 2020</xref>; <xref ref-type="bibr" rid="B33">Wang et al., 2021</xref>; <xref ref-type="bibr" rid="B12">Du et al., 2022</xref>), totaling 728 patients, reported on the effective rate of TCM symptoms. The analysis found homogeneity among the studies (<italic>p</italic> &#x003D; 0.55, <italic>I</italic>
<sup>2</sup> &#x003D; 0), and a fixed-effects model was employed. The findings revealed that, compared to the control group, the experimental group significantly improved the TCM symptomatic effective rate, with a statistically significant difference [RR &#x003D; 1.19, 95% CI (1.12, 1.28), <italic>p</italic> &#x003c; 0.000 01].(<xref ref-type="fig" rid="F5">Figure 5</xref>).</p>
<fig id="F5" position="float">
<label>FIGURE 5</label>
<caption>
<p>Meta-analysis of the effective rate of Chinese medicine syndromes in patients with coronary heart disease angina pectoris treated with modified Danggui Sini Decoction combined with conventional western medicine.</p>
</caption>
<graphic xlink:href="fphar-15-1375795-g005.tif"/>
</fig>
</sec>
<sec id="s3-4-3">
<title>3.4.3 Nitroglycerin usage reduction</title>
<p>Four studies (<xref ref-type="bibr" rid="B23">Lu et al., 2019</xref>; <xref ref-type="bibr" rid="B48">Zifeng, 2019</xref>; <xref ref-type="bibr" rid="B25">Qi-Min, 2020</xref>; <xref ref-type="bibr" rid="B12">Du et al., 2022</xref>), comprising 270 patients, examined the reduction in nitroglycerin usage. These studies showed homogeneity (<italic>p</italic> &#x003D; 0.71, <italic>I</italic>
<sup>2</sup> &#x003D; 0), allowing for a fixed-effects model in the meta-analysis. The outcomes demonstrated that the experimental group significantly reduced nitroglycerin usage compared to the control group, with a statistically significant difference [RR &#x003D; 1.28, 95% CI (1.11, 1.47), <italic>p</italic> &#x003D; 0.0005]. Refer to <xref ref-type="fig" rid="F6">Figure 6</xref>.</p>
<fig id="F6" position="float">
<label>FIGURE 6</label>
<caption>
<p>Meta-analysis of the rate of nitroglycerin reduction in patients with coronary heart disease angina pectoris treated with modified Danggui Sini Decoction in combination with conventional western medicines.</p>
</caption>
<graphic xlink:href="fphar-15-1375795-g006.tif"/>
</fig>
</sec>
<sec id="s3-4-4">
<title>3.4.4 ECG effectiveness rate</title>
<p>The effectiveness of ECG improvements was reported in four studies (<xref ref-type="bibr" rid="B23">Lu et al., 2019</xref>; <xref ref-type="bibr" rid="B48">Zifeng, 2019</xref>; <xref ref-type="bibr" rid="B25">Qi-Min, 2020</xref>; <xref ref-type="bibr" rid="B12">Du et al., 2022</xref>) with a total of 270 patients. The analysis showed homogeneity (<italic>p</italic> &#x003D; 0.80, <italic>I</italic>
<sup>2</sup> &#x003D; 0), and a fixed-effects model was utilized. Results indicated that the trial group significantly improved ECG efficiency in patients compared to the control group, with a statistically significant difference [RR &#x003D; 1.27, 95% CI (1.06, 1.51), <italic>p</italic> &#x003D; 0.008] (<xref ref-type="fig" rid="F7">Figure 7</xref>).</p>
<fig id="F7" position="float">
<label>FIGURE 7</label>
<caption>
<p>Meta-analysis of the ECG efficiency of modified Danggui Sini Decoction combined with conventional western drugs in the treatment of patients with angina pectoris in coronary artery disease.</p>
</caption>
<graphic xlink:href="fphar-15-1375795-g007.tif"/>
</fig>
</sec>
<sec id="s3-4-5">
<title>3.4.5 Number of angina attacks</title>
<p>Ten studies (<xref ref-type="bibr" rid="B45">Zhang and Wang, 2017</xref>; <xref ref-type="bibr" rid="B23">Lu et al., 2019</xref>; <xref ref-type="bibr" rid="B1">Chen et al., 2020</xref>; <xref ref-type="bibr" rid="B25">Qi-Min, 2020</xref>; <xref ref-type="bibr" rid="B6">Cui et al., 2021</xref>; <xref ref-type="bibr" rid="B30">Wang, 2021</xref>; <xref ref-type="bibr" rid="B33">Wang et al., 2021</xref>; <xref ref-type="bibr" rid="B12">Du et al., 2022</xref>; <xref ref-type="bibr" rid="B20">Li, 2022</xref>; <xref ref-type="bibr" rid="B14">Hui and Qian, 2023</xref>), involving 1,016 patients, reported on the number of angina episodes. There was significant heterogeneity among the studies (<italic>p</italic> &#x003c; 0.00001, <italic>I</italic>
<sup>2</sup> &#x003D; 96%); thus, a random-effects model was adopted, which revealed that the trial group effectively reduced the number of angina episodes compared with the control group, with a statistically significant difference (MD &#x003D; &#x2212;1.87, 95% CI [&#x2212;2.63, &#x2212;1.10], <italic>p</italic> &#x003c; 0.00001) (<xref ref-type="fig" rid="F8">Figure 8</xref>).</p>
<fig id="F8" position="float">
<label>FIGURE 8</label>
<caption>
<p>Meta-analysis of the combination of modified Danggui Sini Decoction with conventional western drugs to reduce the number of angina pectoris in patients with coronary heart disease angina pectoris.</p>
</caption>
<graphic xlink:href="fphar-15-1375795-g008.tif"/>
</fig>
</sec>
<sec id="s3-4-6">
<title>3.4.6 Duration of angina pectoris</title>
<p>Ten studies (<xref ref-type="bibr" rid="B45">Zhang and Wang, 2017</xref>; <xref ref-type="bibr" rid="B23">Lu et al., 2019</xref>; <xref ref-type="bibr" rid="B1">Chen et al., 2020</xref>; <xref ref-type="bibr" rid="B25">Qi-Min, 2020</xref>; <xref ref-type="bibr" rid="B6">Cui et al., 2021</xref>; <xref ref-type="bibr" rid="B30">Wang, 2021</xref>; <xref ref-type="bibr" rid="B33">Wang et al., 2021</xref>; <xref ref-type="bibr" rid="B12">Du et al., 2022</xref>; <xref ref-type="bibr" rid="B20">Li, 2022</xref>; <xref ref-type="bibr" rid="B14">Hui and Qian, 2023</xref>), encompassing 1,016 patients, reported on the duration of angina pectoris. Significant heterogeneity was observed among the studies (<italic>p</italic> &#x003c; 0.00001, <italic>I</italic>
<sup>2</sup> &#x003D; 89%), prompting the use of a random-effects model. The meta-analysis revealed that the trial group significantly reduced the duration of angina pectoris compared to the control group, with a statistically significant difference [MD &#x003D; &#x2212;1.78, 95% CI (&#x2212;2.16, &#x2212;1.39), <italic>p</italic> &#x003c; 0.00001] (<xref ref-type="fig" rid="F9">Figure 9</xref>).</p>
<fig id="F9" position="float">
<label>FIGURE 9</label>
<caption>
<p>Meta-analysis of the combination of modified Danggui Sini Decoction with conventional western drugs to shorten the duration of angina in patients with coronary angina pectoris.</p>
</caption>
<graphic xlink:href="fphar-15-1375795-g009.tif"/>
</fig>
</sec>
<sec id="s3-4-7">
<title>3.4.7 Indicators of cardiac function</title>
<p>Five studies (<xref ref-type="bibr" rid="B23">Lu et al., 2019</xref>; <xref ref-type="bibr" rid="B1">Chen et al., 2020</xref>; <xref ref-type="bibr" rid="B30">Wang, 2021</xref>; <xref ref-type="bibr" rid="B33">Wang et al., 2021</xref>; <xref ref-type="bibr" rid="B14">Hui and Qian, 2023</xref>) evaluated CO and LVEF indices, while three studies (<xref ref-type="bibr" rid="B1">Chen et al., 2020</xref>; <xref ref-type="bibr" rid="B33">Wang et al., 2021</xref>; <xref ref-type="bibr" rid="B14">Hui and Qian, 2023</xref>) examined LVEDD. Due to heterogeneity among the findings, a random-effects model was employed for the meta-analysis. The results indicated improvements in CO [MD &#x003D; 0.92, 95% CI (0.72, 1.11), <italic>p</italic> &#x003c; 0.00001], LVEF [MD &#x003D; 6.14, 95% CI (3.41, 8.87), <italic>p</italic> &#x003c; 0.0001], and LVEDD [MD &#x003D; &#x2212;8.32, 95% CI (&#x2212;9.92, &#x2212;6.73), <italic>p</italic> &#x003c; 0.00001], demonstrating that the experimental group significantly enhanced cardiac function compared to the control group (<xref ref-type="fig" rid="F10">Figure 10</xref>).</p>
<fig id="F10" position="float">
<label>FIGURE 10</label>
<caption>
<p>Meta-analysis of modified Danggui Sini Decoction combined with conventional western drugs to improve cardiac function in patients with coronary angina pectoris.</p>
</caption>
<graphic xlink:href="fphar-15-1375795-g010.tif"/>
</fig>
</sec>
<sec id="s3-4-8">
<title>3.4.8 TCM symptom score</title>
<p>Five studies (<xref ref-type="bibr" rid="B48">Zifeng, 2019</xref>; <xref ref-type="bibr" rid="B15">Jia, 2020</xref>; <xref ref-type="bibr" rid="B6">Cui et al., 2021</xref>; <xref ref-type="bibr" rid="B30">Wang, 2021</xref>; <xref ref-type="bibr" rid="B20">Li, 2022</xref>), involving 392 patients, assessed TCM symptom scores. The studies showed homogeneity (<italic>p</italic> &#x003D; 0.84, <italic>I</italic>
<sup>2</sup> &#x003D; 0), leading to the application of a fixed-effect model. The analysis showed that the experimental group significantly reduced TCM syndromic scores compared to the control group, with a statistically significant difference [MD &#x003D; &#x2212;2.90, 95% CI (&#x2212;3.47, &#x2212;2.34), <italic>p</italic> &#x003c; 0.00001] (<xref ref-type="fig" rid="F11">Figure 11</xref>).</p>
<fig id="F11" position="float">
<label>FIGURE 11</label>
<caption>
<p>Meta-analysis of the improvement of TCM symptom scores in patients with angina pectoris of coronary artery disease by combining modified Danggui Sini Decoction with conventional western drugs.</p>
</caption>
<graphic xlink:href="fphar-15-1375795-g011.tif"/>
</fig>
</sec>
<sec id="s3-4-9">
<title>3.4.9 Seattle angina questionnaire</title>
<p>Three studies (<xref ref-type="bibr" rid="B45">Zhang and Wang, 2017</xref>; <xref ref-type="bibr" rid="B23">Lu et al., 2019</xref>; <xref ref-type="bibr" rid="B12">Du et al., 2022</xref>), comprising 272 patients, referenced the Seattle Angina Questionnaire. Given the homogeneity of these studies, a random-effects model was conducted for meta-analysis. The findings highlighted significant improvements in the limitation of physical activity [MD &#x003D; 7.50, 95% CI (4.82, 10.18), <italic>p</italic> &#x003c; 0.00001], stability of angina [MD &#x003D; 9.18, 95% CI (7.25, 11.11), <italic>p</italic> &#x003c; 0.00001], frequency of anginal attacks [MD &#x003D; 7.23, 95% CI (3.99, 10.47), <italic>p</italic> &#x003c; 0.00001], treatment satisfaction [MD &#x003D; 7.35, 95% CI (5.90, 8.79), <italic>p</italic> &#x003c; 0.0001], and disease awareness (MD &#x003D; 9.47, 95% CI (7.42, 11.51), <italic>p</italic> &#x003c; 0.00001), demonstrating the experimental group&#x2019;s effectiveness in improving patient symptoms of angina compared to the control group (<xref ref-type="fig" rid="F12">Figure 12</xref>).</p>
<fig id="F12" position="float">
<label>FIGURE 12</label>
<caption>
<p>Meta-analysis of the improvement of SAQ scores in patients with coronary angina pectoris by combining modified Danggui Sini Decoction with conventional western drugs.</p>
</caption>
<graphic xlink:href="fphar-15-1375795-g012.tif"/>
</fig>
</sec>
<sec id="s3-4-10">
<title>3.4.10 NT-proBNP</title>
<p>Two studies (<xref ref-type="bibr" rid="B1">Chen et al., 2020</xref>; <xref ref-type="bibr" rid="B44">Zhang, 2020</xref>) assessed NT-proBNP levels in 156 patients. Given the homogeneity observed among the studies (<italic>p</italic> &#x003D; 0.42, &#x003D; 0), a fixed-effects model was employed for the meta-analysis. The results demonstrated that, compared to the control group, the experimental group significantly reduced NT-ProBNP levels, with a statistically significant difference [MD &#x003D; &#x2212;333.63, 95% CI (&#x2212;362.00, &#x2212;305.25), <italic>p</italic> &#x003c; 0.00001] (<xref ref-type="fig" rid="F13">Figure 13</xref>).</p>
<fig id="F13" position="float">
<label>FIGURE 13</label>
<caption>
<p>Meta-analysis of modified Danggui Sini Decoction combined with conventional western drugs to improve NT-ProBNP in patients with coronary angina pectoris.</p>
</caption>
<graphic xlink:href="fphar-15-1375795-g013.tif"/>
</fig>
</sec>
<sec id="s3-4-11">
<title>3.4.11 Inflammatory factors</title>
<p>Two studies (<xref ref-type="bibr" rid="B48">Zifeng, 2019</xref>; <xref ref-type="bibr" rid="B44">Zhang, 2020</xref>) examined IL-6, TNF-&#x3b1;, and hs-CRP levels. After testing for homogeneity, a fixed-effects model was applied for the meta-analysis. The findings indicated significant reductions in IL-6 [MD &#x003D; &#x2212;5.25, 95% CI (&#x2212;5.88, &#x2212;4.61), <italic>p</italic> &#x003c; 0.00001], TNF&#x2013;&#x3b1; (MD &#x003D; &#x2212;8.33, 95% CI (&#x2212;10.25, &#x2212;6.41), <italic>p</italic> &#x003c; 0.00001), and hs-CRP [MD &#x003D; &#x2212;5.30, 95% CI (&#x2212;6.02, &#x2212;4.57), <italic>p</italic> &#x003c; 0.00001] in the experimental group compared to the control group, effectively reducing inflammatory markers (<xref ref-type="fig" rid="F14">Figure 14</xref>).</p>
<fig id="F14" position="float">
<label>FIGURE 14</label>
<caption>
<p>Meta-analysis of the improvement of inflammatory factors in patients with coronary heart disease angina pectoris by combining modified Danggui Sini Decoction with conventional western medicines.</p>
</caption>
<graphic xlink:href="fphar-15-1375795-g014.tif"/>
</fig>
</sec>
<sec id="s3-4-12">
<title>3.4.12 Adverse events rates</title>
<p>Two studies (<xref ref-type="bibr" rid="B44">Zhang, 2020</xref>; <xref ref-type="bibr" rid="B33">Wang et al., 2021</xref>) reported on adverse events, noting that two patients in the experimental group experienced thirst, while 10 patients in the control group suffered from decreased appetite, diarrhea, and gastrointestinal symptoms. The homogeneity test showed consistency among the studies. The meta-analysis results [OR &#x003D; 0.23, 95% CI (0.06, 0.92), <italic>p</italic> &#x003D; 0.04] indicated that the experimental group had a better safety profile than the control group. These results are depicted in <xref ref-type="fig" rid="F15">Figure 15</xref>.</p>
<fig id="F15" position="float">
<label>FIGURE 15</label>
<caption>
<p>Meta-analysis of the improvement of adverse events rates in patients with coronary heart disease angina pectoris by combining modified Danggui Sini Decoction with conventional western medicines.</p>
</caption>
<graphic xlink:href="fphar-15-1375795-g015.tif"/>
</fig>
</sec>
<sec id="s3-4-13">
<title>3.4.13 Risk of publication bias assessment</title>
<p>A funnel plot was used to evaluate the risk of publication bias for the outcome indicators concerning the number of angina episodes and the duration of angina. The left-right asymmetry observed in the plot of each study point suggests a potential for publication bias (<xref ref-type="fig" rid="F16">Figures 16A,B</xref>).</p>
<fig id="F16" position="float">
<label>FIGURE 16</label>
<caption>
<p>
<bold>(A)</bold> Funnel plot of the number of episodes of angina pectoris in coronary artery disease treated with modified Danggui Sini Decoction combined with conventional western drugs. <bold>(B)</bold> Funnel plot of duration of angina pectoris in coronary artery disease treated with modified Danggui Sini Decoction in combination with conventional western drugs.</p>
</caption>
<graphic xlink:href="fphar-15-1375795-g016.tif"/>
</fig>
</sec>
</sec>
<sec id="s3-5">
<title>3.5 Evidence quality evaluation</title>
<p>The GRADE evaluation results of the evidence of Danggui Sini Tang in assisting the treatment of coronary heart disease angina pectoris patients can be found in <xref ref-type="sec" rid="s11">Supplementary Material</xref> S2. The main reasons for the downgrading of bias risk include bias caused by missing blinding and insufficient allocation concealment in the included studies; The main reason for the inconsistency degradation is that there is significant heterogeneity among some studies without reasonable explanations, which may affect the scientific validity of research methods and the reliability of research results; The main reason for the degradation of imprecision is that the confidence interval is too large, which affects the accuracy of the evidence.</p>
</sec>
</sec>
<sec id="s4" sec-type="discussion">
<title>4 Discussion</title>
<p>According to the China Cardiovascular Health and Disease Report 2019, cardiovascular disease affects approximately 330 million individuals in China, with the burden of disease on the rise (<xref ref-type="bibr" rid="B18">Layang, 2016</xref>). Among these, around 11 million are currently suffering from CHD, highlighting the growing focus on the prevention and treatment of CHD. Angina pectoris, a significant subtype of CHD, is noted for its high prevalence, mortality rate, treatment costs, and generally poor prognosis (<xref ref-type="bibr" rid="B31">Wang et al., 2023</xref>). Consequently, there is an increasing interest in traditional medicines, with the integration of Chinese and Western medicine in CHD treatment emerging as a 21st-century focal point. This approach has shown substantial progress in enhancing physical activity tolerance and symptom relief and is gaining acceptance among healthcare professionals and patients (<xref ref-type="bibr" rid="B37">Yafang et al., 2019</xref>). Thus, exploring and understanding the trends and patterns in the combined use of traditional Chinese and Western medicines for CHD treatment is essential.</p>
<p>Coronary artery disease, resulting from coronary atherosclerosis or thrombosis, leads to myocardial ischemia and hypoxia due to the narrowing or blockage of the artery lumen. The inflammatory response and abnormal platelet activation are pivotal in thrombosis, forming the pathological basis of coronary artery thrombosis (<xref ref-type="bibr" rid="B27">Ruddox et al., 2017</xref>). Percutaneous coronary intervention (PCI), a primary treatment, does not alter the underlying pathology, hence the risk of in-stent thrombosis and coronary in-stent restenosis (ISR) remains, potentially causing adverse cardiovascular events (<xref ref-type="bibr" rid="B29">Wan, 2023</xref>). Post-PCI, antiplatelet therapy is essential, with dual antiplatelet therapy comprising aspirin and clopidogrel recommended for managing coronary artery disease. Clopidogrel, an adenosine diphosphate (ADP) receptor antagonist, together with aspirin, which does not inhibit ADP-induced platelet aggregation alone, can prevent thrombin and platelet activation when combined. Nonetheless, clopidogrel resistance often necessitates increased dosages, the addition of a third antiplatelet drug (aspirin, clopidogrel, cilostazol), P2Y12 receptor antagonists, or the incorporation of TCM (<xref ref-type="bibr" rid="B22">Liu et al., 2013</xref>; <xref ref-type="bibr" rid="B43">Yu and Wang, 2014</xref>; <xref ref-type="bibr" rid="B47">Zhou and Wang, 2014</xref>). Notably, the China Food and Drug Administration has endorsed over 200 proprietary Chinese medicines for adjunctive or complementary angina pectoris treatments, significantly contributing to the reduction of primary end-stage events, anginal episodes, and improvement in electrocardiograms (<xref ref-type="bibr" rid="B26">Quan et al., 2004</xref>).</p>
<p>Modified Danggui Sini Decoction, originally detailed in Zhang Zhongjing&#x2019;s &#x201c;Shang Han Lun,&#x201d; comprises Angelicae Sinensis Radix, Ramulus Cinnamomi, Asarum sieboldii Miq, Tetrapanax papyriferus, and Paeonia lactiflora Pall. It is recognized for its ability to warm Yang, activate the veins, promote blood circulation, and eliminate blood stasis (<xref ref-type="bibr" rid="B35">Xiong et al., 2015</xref>). Modern research has identified that Angelica sinensis contains diverse components such as volatile oils, terpenes, organic acids, polysaccharides, flavonoids, alkaloids, trace elements, and amino acids (<xref ref-type="bibr" rid="B41">Yi et al., 2005</xref>; <xref ref-type="bibr" rid="B40">Yi et al., 2007a</xref>; <xref ref-type="bibr" rid="B42">Yi et al., 2007b</xref>). Recent studies have isolated &#x201c;ferulic acid&#x201d; from Angelica sinensis, highlighting its vascular protective properties and capacity to inhibit platelet aggregation (<xref ref-type="bibr" rid="B8">Li et al., 2006</xref>). Additionally, the volatile oil from Angelica sinensis has been found effective in alleviating vasospasm and expanding blood vessels (<xref ref-type="bibr" rid="B26">Quan et al., 2004</xref>). Cinnamaldehyde, derived from Cinnamomum cassia, inhibits collagen- and thrombin-induced platelet aggregation both <italic>in vitro</italic> and <italic>in vivo</italic> (<xref ref-type="bibr" rid="B13">Huang et al., 2006</xref>). Compounds such as caffeic acid, isochlorogenic acid C, chlorogenic acid, and wild baicalin from Cynanchum officinale exhibit vasodilatory and smooth muscle relaxing properties, besides inhibiting thrombosis <italic>in vivo</italic> (<xref ref-type="bibr" rid="B2">CHEN et al., 2010</xref>). The primary active constituents of Paeonia lactiflora, mainly terpenes and terpene glycosides, act on vascular endothelium to dilate vascular smooth muscle, enhancing myocardial blood flow and oxygen and blood supply (<xref ref-type="bibr" rid="B38">Yan et al., 2023</xref>). Pharmacological studies have demonstrated that extracts from Tongzhi exhibit significant antithrombotic and anti-inflammatory activities, effectively preventing thrombus formation (<xref ref-type="bibr" rid="B36">Xue et al., 2019</xref>). Ginger has been shown to improve blood lipids, facilitate cholesterol excretion, reduce arteriosclerosis (AS) progression, and inhibit platelet aggregation through the activation of signaling pathways such as PI3K-Akt, IL-17, HIF-1, and p53, and the regulation of genes like TP53, MAPK3, MAPK1, AKT1, ESR1, and JUN, thereby mitigating hypoxia-induced cardiac muscle injury and aiding in the management of angina pectoris (<xref ref-type="bibr" rid="B16">Jiang et al., 2023</xref>). Various studies confirm that Angelica Siwei Tang possesses anticoagulant and antithrombotic effects, enhances vascular perfusion, and offers anti-inflammatory and analgesic benefits, thereby protecting cardiomyocytes and improving clinical outcomes.</p>
<p>This study was informed by the integration of Chinese and Western medicinal theories, adopting an evidence-based approach to demonstrate that modified Danggui Sini Decoction, in conjunction with conventional Western medications, can effectively enhance clinical outcomes for patients with coronary heart disease coexisting with angina pectoris. This includes improvements in inflammatory markers, cardiac function, and frequency of angina episodes, thereby contributing to disease progression control. Nonetheless, this study is subject to certain limitations. Firstly, among the 13 included RCTs, 3 (<xref ref-type="bibr" rid="B45">Zhang and Wang, 2017</xref>; <xref ref-type="bibr" rid="B48">Zifeng, 2019</xref>; <xref ref-type="bibr" rid="B44">Zhang, 2020</xref>) did not clearly detail their randomization methods; none of the studies disclosed the concealment of allocation schemes or the application of blinding. Secondly, the dosage and treatment duration of modified Danggui Sini Decoction varied across the studies. Thirdly, the geographical location of all included RCTs being in China introduces potential geographic bias, all of which could influence the outcomes. These conclusions warrant confirmation through high-quality research.</p>
</sec>
<sec id="s5" sec-type="conclusion">
<title>5 Conclusion</title>
<p>Drawing from the existing evidence, fthe combination of modified Danggui Sini Decoction and conventional Western medicines significantly enhances clinical efficiency, cardiac function, and the management of angina episodes and inflammatory markers, alongside notably improving SAQ scores compared to control treatments, thus offering increased safety. This provides substantiated evidence for its adjunctive use in treating this condition. However, due to several limitations, these findings require further validation through more rigorous clinical studies and foundational research in the future.</p>
</sec>
</body>
<back>
<sec id="s6" sec-type="data-availability">
<title>Data availability statement</title>
<p>The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.</p>
</sec>
<sec id="s7">
<title>Author contributions</title>
<p>HW: Writing&#x2013;original draft, Writing&#x2013;review and editing. CL: Writing&#x2013;original draft, Writing&#x2013;review and editing. XG: Writing&#x2013;original draft, Writing&#x2013;review and editing. JY: Funding acquisition, Supervision, Validation, Writing&#x2013;review and editing. YZ: Funding acquisition, Supervision, Validation, Writing&#x2013;review and editing.</p>
</sec>
<sec id="s8" sec-type="funding-information">
<title>Funding</title>
<p>The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported through funding to State Administration of Traditional Chinese Medicine project [No. HED(2022)75].</p>
</sec>
<sec id="s9" sec-type="COI-statement">
<title>Conflict of interest</title>
<p>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.</p>
</sec>
<sec id="s10" sec-type="disclaimer">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
<sec id="s11">
<title>Supplementary material</title>
<p>The Supplementary Material for this article can be found online at: <ext-link ext-link-type="uri" xlink:href="https://www.frontiersin.org/articles/10.3389/fphar.2024.1375795/full#supplementary-material">https://www.frontiersin.org/articles/10.3389/fphar.2024.1375795/full&#x23;supplementary-material</ext-link>
</p>
<supplementary-material xlink:href="DataSheet1.pdf" id="SM1" mimetype="application/pdf" xmlns:xlink="http://www.w3.org/1999/xlink"/>
</sec>
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