| Objective:To evaluate and compare the efficacy and safety of different heat-clearing and phlegmresolving formulae in the treatment of coronary heart disease angina pectoris with phlegm-heat syndrome through a systematic review and network meta-analysis,and to assess the quality of evidence for different outcome measures using the GRADE methodology.Methods:RCT studies on the treatment of coronary heart disease angina pectoris with phlegm-heat syndrome using heat-clearing and phlegm-resolving formulae were retrieved from eight databases including CNKI,WanFang,VIP,CBM,PubMed,the Cochrane Library,Embase,and Web of Science,from inception to January 31,2023.Literature screening and data extraction were conducted according to inclusion and exclusion criteria.The Cochrane Handbook 5.1.0 was used to assess the risk of bias in the included studies,and a summary of bias risk table and a bias risk graph were created using Review Manager 5.4 software.Network meta-analysis was conducted using STATA 15.1 software to generate network evidence plots,network contribution plots,prediction interval plots,comparison-adjusted funnel plots,league tables,and cumulative probability plots for 8 outcome measures.Safety of the interventions was assessed by evaluating two safety outcome measures.The quality of evidence for each outcome measure was evaluated using the GRADE methodology.Results:1.Literature Retrieval and Screening ResultsAtotal of 8586 articles were initially retrieved from 8 databases including CNKI,WanFang,VIP,CBM,PubMed,the Cochrane Library,Embase,and Web of Science,from inception to January 31,2023.Finally,66 clinical RCT studies involving 5127 patients were included,which evaluated 9 different formulas with the efficacy of clearing heat and resolving phlegm,including modified Xiaoxian Xiong Decoction,modified Chaihu Xianxiong Decoction,modified Chaixian Danshen Decoction,modified Xianxiong Zhuyu Decoction,modified Wendan Decoction,modified Huanglian Wendan Decoction,Lianxia Ningxin Granule,modified Guanxin Xiaoban Decoction,Jiedu Tongmai Capsule.2.Risk of bias assessmentRegarding the generation of random sequence,32 studies were assessed as low risk(26 studies used random number tables,1 used drawing lots,1 used computer-generated randomization,1 used a randomized block design,1 used a coin-tossing method,and 2 used random allocation);1 study was assessed as high risk(participants were grouped according to TCM syndrome differentiation,clinical manifestations,ECG and laboratory examination),and the remainder were unclear.One study mentioned allocation concealment,blinding of participants and clinicians,and blinding of outcome assessors and statisticians,while the remaining studies were unclear.Sixty-four studies had complete outcome data and were assessed as low risk;1 study did not report how to handle missing data and was assessed as high risk,and the remainder were unclear.Fifty-one studies provided a complete description of outcome measures and were assessed as low risk,while 14 studies did not report results for some observed outcomes and were assessed as high risk,and the remainder were unclear.Baseline comparability between the two groups was reported in 65 studies.3.Network Meta-analysis ResultsOut of 69 original randomized controlled trials(RCTs),18 reported overall clinical effectiveness with a total sample size of 1825,involving 9 intervention measures.There were 8 direct comparisons and 36 pairwise comparisons,among which 14 comparisons showed statistically significant differences.The intervention with the highest SUCRA value was conventional Western medicine treatment plus Lianxia Ningxin Granule(92.1%).37 studies reported the efficacy of angina pectoris,with a total sample size of 2560,involving 11 intervention measures.There were 10 direct comparisons and 55 pairwise comparisons,among which 18 comparisons showed statistically significant differences.The intervention with the highest SUCRA value was conventional Western medicine treatment plus modified Guanxin Xiaoban Decoction(83.1%).24 studies reported the frequency and duration of angina attacks,with a total sample size of 2052,involving 8 intervention measures.There were 7 direct comparisons and 28 pairwise comparisons,among which 6 comparisons showed statistically significant differences.The intervention with the highest SUCRA value was conventional Western medicine treatment plus modified Xiaoxian Xiong Decoction(90.0%)(91.7%).17 studies reported the nitroglycerin cessation rate,with a total sample size of 1093,involving 8 intervention measures.There were 7 direct comparisons and 28 pairwise comparisons,among which 7 comparisons showed statistically significant differences.The intervention with the highest SUCRA value was conventional Western medicine treatment plus modified Chaixian Danshen Decoction(75.4%).29 studies reported the efficacy on electrocardiogram,with a total sample size of 1975,involving 9 intervention measures.There were 8 direct comparisons and 36 pairwise comparisons,among which 18 comparisons showed statistically significant differences.The intervention with the highest SUCRA value was conventional Western medicine treatment plus modified Chaihu Xianxiong Decoction(77.3%).31 studies reported the efficacy on Traditional Chinese Medicine(TCM)syndrome,with a total sample size of 2036,involving 10 intervention measures.There were 9 direct comparisons and 45 pairwise comparisons,among which 16 comparisons showed statistically significant differences.The intervention with the highest SUCRA value was conventional Western medicine treatment plus modified Xianxiong Zhuyu Decoction(81.3%).16 studies reported the TCM syndrome score,with a total sample size of 1437,involving 10 intervention measures.There were 10 direct comparisons and 45 pairwise comparisons,among which 16 comparisons showed statistically significant differences.The intervention with the highest SUCRA value was conventional Western medicine treatment plus modified Wendan Decoction(99.8%).4.Safety indicatorsOut of 30 studies,adverse event rates were reported in all,with 22 studies reporting a rate of 0 adverse events.Among the remaining 8 studies,a small number of patients experienced adverse events such as rash,dizziness,headache,nausea,vomiting,diarrhea,bloating,and hypotension.And 8 studies showed no statistically significant difference in the incidence of adverse events between the control and treatment groups.Three studies reported the incidence of cardiovascular adverse events,and the treatment group had a lower incidence of cardiovascular adverse events compared to the control group.5.Quality of evidence ratingThe evidence quality rating for 8 outcome measures was assessed,with no outcome measures rated as high(HIGH)quality.A total of 26 outcome measures(8.64%)were rated as moderate(MODERATE)quality,104 outcome measures(34.55%)were rated as low(LOW)quality,and 171 outcome measures(56.81%)were rated as very low(VERY LOW)quality.The overall evidence quality for the outcome measure of duration of angina is low,while the overall evidence quality for the remaining outcome measures is very low.The main factors leading to downgrading of evidence quality were:1)medium or higher risk of bias;2)inconsistency between prediction intervals and credible intervals;3)indirect evidence;4)small sample size;and 5)publication bias.Conclusion:1.Regarding efficacyDifferent outcomes have different rankings in terms of the efficacy of Qingre Huatan formula for treating coronary heart disease angina with phlegm-heat syndrome.Lianxia Ningxin Granule has a significant advantage in improving the overall clinical efficacy rate;Guanxin Xiaoban Decoction has a greater advantage in improving the efficacy of angina;Xiaoxian Xiong Decoction is more effective in reducing the frequency and duration of angina attacks;Chaixian Danshen Decoction is more conducive to improving the efficacy of nitroglycerin cessation;Chaihu Xianxiong Decoction is more conducive to improving the efficacy of electrocardiogram;Xianxiong Zhuyu Decoction and modified Wendan Decoction have a greater advantage in improving traditional Chinese medicine(TCM)syndrome efficacy and TCM syndrome score.2.Regarding safetyThe safety of 9 types of Qingre Huatan formula is good,with no possibility of increasing the incidence of adverse reactions or cardiovascular adverse events.3.Regarding evidence quality ratingThe evidence quality rating of all outcome indicators is moderate,low,and very low,with a highest proportion of very low-quality evidence.The outcome measures of overall clinical effectiveness rate,efficacy in angina,frequency of angina attacks,nitroglycerin withdrawal rate,efficacy in electrocardiography,efficacy in traditional Chinese medicine patterns,and traditional Chinese medicine pattern score have an overall evidence quality of very low.The overall evidence quality for the outcome measure of duration of angina is low.Future clinical studies with multi-center,large sample,and high-quality RCTs are needed to validate the conclusions of this study. |
PDF Full Text Request