The efficacy of Chinese herbal drugs for adults with angina pectoris: Bayesian network meta-analysis of 331 RCTs involving 36,467 individuals.

ETHNOPHARMACOLOGICAL RELEVANCE: Hundreds of randomized controlled trials (RCT) on Chinese herbal drugs (CHDs) including Shexiang baoxin pill (BXP), compound Danshen dripping pill (DSP), compound Danshen tablet (DST), Suxiao jiuxin pill (JXP), Naoxintong capsule (NXT), Tongxinluo capsule (TXL), and Di'ao xinxuekang capsule (XXK) and conventional chemical drugs, such as isosorbide dinitrate (ISDN), for angina pectoris are available but have not been evaluated by a PRISMA-compliant network meta-analysis (NMA). AIM OF THE STUDY: This study aimed to compare the efficacy of nine anti-anginal drugs through NMA on RCTs. METHODS: RCTs of drug treatment for adult patients with angina pectoris for improvements in symptoms and electrocardiography were retrieved. Odds ratios and 95% credible intervals were computed to measure effect sizes. RCT quality was evaluated with the Cochrane risk of bias tool. Evidence synthesis was performed with Bayesian NMA. Essential analyses including subgroup analysis, sensitivity analysis, meta-regression analysis, publication bias analysis, and ranking analysis were conducted to assess the robustness of efficacies. Evidence strength was assessed with the GRADE approach. RESULTS: A total of 331 RCTs with 36,467 participants were eligible. The overall quality of all included RCTs was low. Overall efficacy estimates from different approaches of evidential synthesis found that BXP, TXL, and DSP were more efficacious than DST and ISDN. Essential analyses indicated consistent efficacy estimates, insignificant publication bias, and corroborative ranking results. The overall GRADE evidence strength was low. CONCLUSION: This comprehensive Bayesian NMA found BXP, TXL, and DSP to be the top three candidates among the seven tested CHDs for treating adults suffering from angina pectoris. However, the quality and the evidence strength of eligible RCTs were low. Further high-quality RCTs with more outcome measures and their NMAs are warranted. REGISTRATION: PROSPERO CRD42014007035.

How efficacious are traditional Chinese medicine injections in treating angina pectoris? A network meta-analysis of randomized controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: Over 50 million adults in China suffer from angina pectoris, which are often treated with traditional Chinese medicine injections (TCMIs). However, the efficacies of TCMIs and conventional drugs as determined by randomized controlled trials (RCTs) were not rigorously compared with one another by network meta-analysis (NMA). This PRISMA-compliant NMA aimed to compare the efficacy and assess the evidence strengths of 24 TCMIs in treating adults with angina pectoris of RCTs. MATERIALS AND METHODS: Following the protocol (PROSPERO registration number CRD42018117720), the RCTs that compared any TCMI with another TCMI or conventional drug on outcome measures including symptomatic and electrocardiography improvements were included. The quality of included RCTs was assessed with the Cochrane's risk of bias 2 tool. Frequentist statistical analyses were performed, including NMA, pairwise meta-analysis (PMA), subgroup analysis, sensitivity analysis, meta-regression, and publication bias analysis. The certainty of evidence was assessed with the GRADE approach. RESULTS: Totally, 556 eligible RCTs with 57015 participants were identified while the quality of all but five included RCTs was poor. The significant efficacy estimates and insignificant heterogeneity assessment from PMA and NMA indicated that nearly all TCMIs were more efficacious than conventional treatments for angina pectoris. Adequate subgroup and sensitivity analyses found the robust and consistent results. However, the evidence strengths of meta-analyses were assessed as very low to low due to the high risk of RCTs. The comprehensive efficacy estimates suggested that 4 TCMIs (HH, Honghua injection; HHH, Honghua Huangsesu injection; GLP, Gualoupi injection; and SM, Shenmai injection) was the best anti-anginal drugs for adults with angina pectoris. CONCLUSION: TCMIs appear to be efficacious for angina pectoris, although evidence evaluation of high-quality RCTs of TCMIs would be necessary. In particular, randomization and blinding procedures of the RCTs should be explicated to meet the CONSORT requirements.

Comparative efficacy of single-inhaler triple therapies for COPD: A protocol for systematic review and network meta-analysis.

INTRODUCTION: 2021 Global Initiative for Chronic Obstructive Lung Disease (GOLD) Reports recommends that patients with clinically significant symptoms and exacerbations of chronic obstructive pulmonary disease (COPD) should escalate to triple therapy, a combined use of inhaled corticosteroids (ICS), long-acting muscarinic antagonists (LAMA) and long-acting b2-agonists (LABA)(ICS/LAMA/LABA). Triple therapy in fixed-dose combinations (FDCs), i.e., combining ICS, LABA with LAMA and administrating by a single inhalation device, has appeared in recent years. This study aims to compare the efficacy of triple therapy in FDCs in treating patients with moderate to severe COPD. METHODS AND ANALYSES: Literature search will be conducted on PubMed, Embase and Web of science, according to pre-specified and corresponding search strategies, for relevant reports published since the inception dates of the databases. Randomised controlled trials (RCT) which compared the triple therapy in FDCs with other pharmacological therapies will be included. The Cochrane risk of bias assessment tool (RoB 2) will be used to assess the RCT quality. The outcomes will be analyzed as rate ratios and mean differences under a random-effects model in a frequentist network meta-analysis (NMA). Additional statistical analyses including subgroup analysis, sensitivity analysis, and publication bias analysis will be performed to assess the evidential heterogeneity and robustness. The strength of evidence from the NMA will be evaluated with the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) methods. ETHICS AND DISSEMINATION: No ethics approval is required as this systematic review and network meta-analysis do not collect confidential personal data and do not carry out interventions in treating patients. PROTOCOL REGISTRATION NUMBER: CRD42021240823.

Identification of certain Panax species to be potential substitutes for Panax notoginseng in hemostatic treatments.

Panax notoginseng (Burkill) F. H. Chen ex C. H. Chow (P. notoginseng) is a highly valued Chinese materia medica having a hemostatic effect and mainly used for the treatment of trauma and ischemic cardiovascular diseases. Stringent growth requirements, weak resistance to insect pests and plant diseases, arsenic contamination and continuous cropping constitute hurdles to further increases in the agricultural production of P. notoginseng. This review focuses on the traditional uses (based on traditional Chinese medicine theory), major chemical components, biological activities, pharmacological properties, geographical distributions and historical development of taxonomy of P. notoginseng and its related species in Panax genus, including Panax japonicus C. A. Meyer (P. japonicus), Panax japonicus C. A. Meyer var. major (Burkill) C. Y. Wu et K. M. Feng (P. japonicus var. major) and Panax japonicus C. A. Meyer var. bipinnatifidus (Seem.) C. Y. Wu et K. M. Feng (P. japonicus var. bipinnatifidus) are reviewed. This review sheds light on the origin herbs of Zhujieshen (ZJS) and Zhuzishen (ZZS), e.g., P. japonicas var japonicas, P. japonicus var. major and P. japonicus var. bipinnatifidus could be used as a substitute for P. notoginseng as hemostatic herbs.

Building Molecular Interaction Networks from Microarray Data for Drug Target Screening.

Potential drug targets for the disease treatment can be identified from microarray studies on differential gene expression of patients and healthy participants. Here, we describe a method to use the information of differentially expressed (DE) genes obtained from microarray studies to build molecular interaction networks for identification of pivotal molecules as potential drug targets. The quality control and normalization of the microarray data are conducted with R packages simpleaffy and affy, respectively. The DE genes with adjusted P values less than 0.05 and log fold changes larger than 1 or less than -1 are identified by limma package to construct a molecular interaction network with InnateDB. The genes with significant connectivity are identified by the Cytoscape app jActiveModules. The interactions among the genes within a module are tested by psych package to determine their associations. The gene pairs with significant association and known protein structures according to the Protein Data Bank are selected as potential drug targets. As an example for drug target screening, we demonstrate how to identify potential drug targets from a molecular interaction network constructed with the DE genes of significant connectivity, using a microarray dataset of type 2 diabetes mellitus.

How Efficacious is Danshen (Salvia miltiorrhiza) Dripping Pill in Treating Angina Pectoris? Evidence Assessment for Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: More than 230 randomized controlled trials (RCTs) of danshen dripping pill (DSP) and isosorbide dinitrate (ISDN) in treating angina pectoris after the first preferred reporting items for systematic reviews and meta-analyses-compliant comprehensive meta-analysis were published in 2010. Other meta-analyses had flaws in study selection, statistical meta-analysis, and evidence assessment. This study completed the meta-analysis with an extensive assessment of the evidence. METHODS: RCTs published from 1994 to 2016 on DSP and ISDN in treating angina pectoris for at least 4 weeks were included. The risk of bias (RoB) of included RCTs was assessed with the Cochrane's tool for assessing RoB. Meta-analyses based on a random-effects model were performed on two outcome measures: symptomatic (SYM) and electrocardiography (ECG) improvements. Subgroup analysis, sensitivity analysis, metaregression, and publication bias analysis were also conducted. The evidence strength was evaluated with the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) method. RESULTS: Among the included 109 RCTs with 11,973 participants, 49 RCTs and 5042 participants were new (after 2010). The RoB of included RCTs was high in randomization and blinding. Overall effect sizes in odds ratios for DSP over ISDN were 2.94 (95% confidence interval [CI]: 2.53-3.41) on SYM (n = 108) and 2.37 (95% CI: 2.08-2.69) by ECG (n = 81) with significant heterogeneities (I2 = 41%, p < 0.0001 on SYM and I2 = 44%, p < 0.0001 on ECG). Subgroup, sensitivity, and metaregression analyses showed consistent results without publication bias. However, the evidence strength was low in GRADE. CONCLUSION: The efficacy of DSP was still better than ISDN in treating angina pectoris, but the confidence decreased due to high RoB and heterogeneities.

Comparative Efficacy of Tongxinluo Capsule and Beta-Blockers in Treating Angina Pectoris: Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: There have been no systematic reviews, let alone meta-analyses, of randomized controlled trials (RCTs) comparing tongxinluo capsule (TXL) and beta-blockers in treating angina pectoris. This study aimed to evaluate the efficacy of TXL and beta-blockers in treating angina pectoris by a meta-analysis of eligible RCTs. METHODS: The RCTs comparing TXL with beta-blockers (including metoprolol) in treating angina pectoris were searched and retrieved from databases including PubMed, Chinese National Knowledge Infrastructure, and WanFang Data. Eligible RCTs were selected according to prespecified criteria. Meta-analysis was performed on the odds ratios (OR) of symptomatic and electrocardiographic (ECG) improvements after treatment. Subgroup analysis, sensitivity analysis, meta-regression, and publication biases analysis were conducted to evaluate the robustness of the results. RESULTS: Seventy-three RCTs published between 2000 and 2014 with 7424 participants were eligible. Overall ORs comparing TXL with beta-blockers were 3.40 (95% confidence interval [CI], 2.97-3.89; p<0.0001) for symptomatic improvement and 2.63 (95% CI, 2.29-3.02; p<0.0001) for ECG improvement. Subgroup analysis and sensitivity analysis found no statistically significant dependence of overall ORs on specific study characteristics except efficacy criteria. Meta-regression found no significant except sample sizes for data on symptomatic improvement. Publication biases were statistically significant. CONCLUSION: TXL seems to be more effective than beta-blockers in treating angina pectoris, on the basis of the eligible RCTs. Further RCTs are warranted to reduce publication bias and verify efficacy.

The efficacy of guanxinning injection in treating angina pectoris: systematic review and meta-analysis of randomized controlled trials.

Objective. The randomized controlled trials (RCTs) on Guanxinning injection (GXN) in treating angina pectoris were published only in Chinese and have not been systematically reviewed. This study aims to provide a PRISMA-compliant and internationally accessible systematic review to evaluate the efficacy of GXN in treating angina pectoris. Methods. The RCTs were included according to prespecified eligibility criteria. Meta-analysis was performed to evaluate the symptomatic (SYMPTOMS) and electrocardiographic (ECG) improvements after treatment. Odds ratios (ORs) were used to measure effect sizes. Subgroup analysis, sensitivity analysis, and metaregression were conducted to evaluate the robustness of the results. Results. Sixty-five RCTs published between 2002 and 2012 with 6064 participants were included. Overall ORs comparing GXN with other drugs were 3.32 (95% CI: [2.72, 4.04]) in SYMPTOMS and 2.59 (95% CI: [2.14, 3.15]) in ECG. Subgroup analysis, sensitivity analysis, and metaregression found no statistically significant dependence of overall ORs upon specific study characteristics. Conclusion. This meta-analysis of eligible RCTs provides evidence that GXN is effective in treating angina pectoris. This evidence warrants further RCTs of higher quality, longer follow-up periods, larger sample sizes, and multicentres/multicountries for more extensive subgroup, sensitivity, and metaregression analyses.

Meta-Analysis of Randomized Controlled Trials on the Efficacy of Di'ao Xinxuekang Capsule and Isosorbide Dinitrate in Treating Angina Pectoris.

Objective. Randomized controlled trials (RCTs) on di'ao xinxuekang capsule (XXK) in treating angina pectoris were published only in Chinese and have not been systematically reviewed particularly for comparing XXK with isosorbide dinitrate (ISDN). This study aims to provide a comprehensive PRISMA compliant and internationally accessible systematic review and meta-analysis to evaluate the efficacies of XXK and ISDN in treating angina pectoris. Methods. The RCTs published between 1989 and 2011 on XXK and ISDN in treating angina pectoris were selected according to specific criteria. Meta-analysis was performed to evaluate the symptomatic (SYMPTOMS) and electrocardiographic (ECG) improvements after treatment. Odds ratios (OR) were used to measure effect sizes. Subgroup analysis, sensitivity analysis, and metaregression were conducted to evaluate the robustness of the results. Results. Seven RCTs with 550 participants were eligible. Overall ORs for comparing XXK with ISDN were 4.11 (95% CI : 2.57, 6.55) in SYMPTOMS and 2.37 (95% CI : 1.46, 3.84) in ECG. Subgroup analysis, sensitivity analysis, and metaregression found no significant dependence of overall ORs upon specific study characteristics. Conclusion. The meta-analysis of eligible but limited RCTs demonstrates that XXK seems to be more effective than ISDN in treating angina pectoris. Further RCTs of high quality are warranted to be conducted for update of the results of this meta-analysis.

Could ginseng-based medicines be better than nitrates in treating ischemic heart disease? A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Ginseng-based medicines and nitrates are commonly used in treating ischemic heart disease (IHD) angina pectoris in China. Hundreds of randomized controlled trials (RCTs) reported in Chinese language claimed that ginseng-based medicines can relieve the symptoms of IHD. This study provides the first PRISMA-compliant systematic review with sensitivity and subgroup analyses to evaluate the RCTs comparing the efficacies of ginseng-based medicines and nitrates in treating ischemic heart disease, particularly angina pectoris. METHODS: Past RCTs published up to 2010 on ginseng versus nitrates in treating IHD for 14 or more days were retrieved from major English and Chinese databases, including PubMed, Science Direct, Cochrane Library, WangFang Data, and Chinese National Knowledge Infrastructure. The qualities of included RCTs were assessed with Jadad scale, a refined Jadad scale called M scale, CONSORT 2010 checklist, and Cochrane risk of bias tool. Meta-analysis was performed on the primary outcomes including the improvement of symptoms and electrocardiography (ECG). Subgroup analysis, sensitivity analysis, and meta-regression were performed to evaluate the effects of study characteristics of RCTs, including quality, follow-up periods, and efficacy definitions on the overall effect size of ginseng. RESULTS: Eighteen RCTs with 1549 participants were included. Overall odds ratios for comparing ginseng-based medicines with nitrates were 3.00 (95% CI: 2.27-3.96) in symptom improvement (n=18) and 1.61 (95% CI: 1.20-2.15) in ECG improvement (n=10). Subgroup analysis, sensitivity analysis, and meta-regression found no significant difference in overall effects among all study characteristics, indicating that the overall effects were stable. CONCLUSION: The meta-analysis of 18 eligible RCTs demonstrates moderate evidence that ginseng is more effective than nitrates for treating angina pectoris. However, further RCTs for higher quality, longer follow-up periods, lager sample size, multi-center/country, and are still required to verify the efficacy.

[Systematic review and meta-analysis of randomized controlled trials comparing Chinese patent medicines Compound Danshen Dripping Pills and Di'ao Xinxuekang in treating angina pectoris].

BACKGROUND: Chinese patent medicines Compound Danshen Dripping Pills (DSP) and Di'ao Xinxuekang (DXK) capsules were both found effective in treating angina pectoris. However, there is no systematic review comparing their efficacy. OBJECTIVE: This systematic review aims to compare the efficacy of DSP and DXK in treating angina pectoris based on randomized controlled trials (RCTs) comparing their efficacy. SEARCH STRATEGY: RCT reports published between 1994 and 2011 were retrieved from databases including China Doctoral Dissertations Full-text Database, Chinese Journal Full-text Database, China Master's Theses Full-text Database, Wanfang Data, Cochrane Library, Excerpts Medica Database, ScienceDirect, MEDLINE (EBSCOhost) and PubMed. The last retrieval was performed on April 7, 2011. INCLUSION CRITERIA: RCT reports comparing the effects of DSP and DXK were included, regardless publishing language. DATA EXTRACTION AND ANALYSIS: Included RCT reports were assessed for their study quality by using the Jadad scale and the Cochrane risk of bias tool. Data including overall effect and electrocardiography (ECG) improvements were extracted from the included RCTs for meta-analysis. The effect sizes based on overall and ECG diagnosis were measured by odds ratio (OR) and 95% confidence interval (CI). Subgroup analysis and sensitivity analysis were also performed. RESULTS: Nine RCT reports with 926 participants were included. Eight were scored 2 and the other one was scored 4 by using the Jadad scale. The OR between DSP and DXK based on overall diagnosis was 2.06 (95% CI: 1.03-4.12; P(overall)=0.04). Six out of the nine included RCTs reported ECG data. The OR between DSP and DXK based on the ECG diagnosis was 1.92 (95% CI: 1.23-3.00; P(ECG)=0.004). The OR results were stable under subgroup analysis and sensitivity analysis. CONCLUSION: DSP was consistently more effective than DXK according to meta-analysis, which was verified by subgroup analysis and sensitivity analysis. However, more RCTs of higher quality are needed for further confirmation.

Is danshen (Salvia miltiorrhiza) dripping pill more effective than isosorbide dinitrate in treating angina pectoris? A systematic review of randomized controlled trials.

BACKGROUND: Danshen dripping pill (DSP) is a popular Chinese medicinal product and often compared with isosorbide dinitrate (ISDN) in treating coronary heart disease angina pectoris. Over 100 randomized controlled trials (RCT) have been published in Chinese language but have not been evaluated according to the PRISMA systematic review standard. This study aims to provide a comprehensive and PRISMA-compliant systematic review with sensitivity and subgroup analyses. METHODS: RCTs published between 1994 and 2009 on DSP versus ISDN in treating angina pectoris for 4 or more weeks were retrieved from major databases, including PubMed, Chinese National Knowledge Infrastructure, and WanFang Data. Meta-analysis was performed on the overall effects on symptomatic and electrocardiography (ECG) improvements. Sensitivity analysis was conducted on the study quality of RCTs based on a refined Jadad scale and different efficacy definitions. RESULTS: Sixty RCTs with 6931 participants were included. Summary odds ratios for comparing DSP and ISDN were 2.49 (95% CI 2.03-3.05) by symptoms (n=60) and 2.14 (95% CI 1.82-2.52) by ECG (n=53) according to the basic efficacy definitions and were 1.67 (95% CI 1.45-1.91) by symptoms (n=56) and 1.75 (95% CI 1.51-2.04) by ECG (n=45) according to the stringent efficacy criteria. CONCLUSION: The 60 eligible RCTs indicate that DSP is apparently more effective than ISDN in treating angina pectoris. However, further RCTs of larger scale, multi-centre/country, longer follow-up periods, and higher quality are still required to verify the efficacy of DSP over all anti-anginal therapies.

Is tongxinluo more effective than isosorbide dinitrate in treating angina pectoris? A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Tongxinluo (TXL), consisting of 12 Chinese Materia Medica items catalogued in the Chinese Pharmacopoeia, is commercially available in China, South Korea, and Russia. Hundreds of randomized clinical trials (RCTs) on TXL in treating cardiovascular diseases were conducted and published in China. This study provides a comprehensive Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant systematic review with sensitivity and subgroup analyses to evaluate the evidence about whether TXL is more effective than isosorbide dinitrate (ISDN) in treating ischemic heart disease, particularly angina pectoris. METHODS: RCTs published between 1996 and 2010 on TXL versus ISDN in treating angina pectoris for at least 4 weeks were retrieved from eight bibliographical databases (e.g., MEDLINE,(®) PubMed, Chinese National Knowledge Infrastructure, Cochrane Library, and WanFang Data). The quality of RCTs was assessed with the Jadad scale. Meta-analysis was performed to estimate the overall effects based on symptomatic and electrocardiographic (ECG) improvements. Subgroup analysis, sensitivity analysis, and meta-regression were conducted on the study characteristics of RCTs. RESULTS: Twenty (20) RCTs with a total of 1936 participants were included after eligibility assessment. The Jadad score of all included studies was 2. The means of summary odds ratios (ORs) for comparing TXL and nitrates were 3.30 (95% confidence interval [CI] 2.37-4.58) by symptoms (n=20) and 2.38 (95% CI 1.846-3.09) by ECG (n=18). There was a significant correlation of ORs between symptoms and ECG (ρ=0.77 and p=0.00026). Subgroup analysis, sensitivity analysis, and meta-regression found no significant difference in overall effects among all study characteristics except the years of publication (p=0.0409). CONCLUSIONS: The meta-analysis of 20 eligible RCTs demonstrates moderate evidence that TXL is more effective than ISDN for treating angina pectoris. This result warrants further RCTs of multicenters/countries, larger sample sizes, and higher quality.