| Part I:Systematic reviews and Meta-analysis of combination therapy in coronary heart disease associated with premature ventricular contractionsObjects:this study aims to analyze domestic clinical research literatures of Integrative Medicine on coronary heart disease with premature ventricular contractions by Evidence-based medicine methods during2000-2009year. We also aim to understand the overview of Integrative Medicine on the treatment of coronary heart disease with premature ventricular contractions, grasp the developed trends in this field and meanwhile, filter out the best clinical evidence to provide a basis for the next multi-center randomized controlled clinical trials (RCTs).Methods:(1) Literature Resources:China National Knowledge Infrastructure (CNKI), VIP Chinese journal database, Wanfang database of academic journals (including the Chinese Medical Association Journal), Chinese biomedical literature service system (CBM), Chinese Medical Citation Index (CMCI), Chinese biological medical journal database, as well as in medicine, integrative medicine online database.(2) Retrieval methods and strategies:①Search term: coronary heart disease with premature ventricular contractions, TCM (traditional Chinese medicine, Chinese herbal medicine, Chinese medicine, formulation, Gaowan, acupuncture)/TCM combined. Logic:"+"=and=AND.②the retrieval formula: coronary heart disease with premature ventricular contractions+Traditional Chinese Medicine/Integrative Medicine.③retrieve Period: January2000-December2009.(3) Bibliometric analysis:①Inclusion criteria: clinical research literature of TCM or Integrative Medicine on coronary heart disease with premature ventricular contractions.②Exclusion criteria: non-clinical research literature; literature research has nothing to do with the human coronary heart disease with premature ventricular contractions; purely Western medicine clinical research literature; review, and repeated in each database literature.③Two reviewers independently screened the selected literatures and extracted the data, then analyzed them from the literature annual amount of source areas and periodicals distribution measure involving distribution of TCM literature research directions.(4) Systematic reviews and Meta-analysis of RCTs:①Inclusion criteria: clinical research literatures of Integrative Medicine on coronary heart disease with premature ventricular contractions, which content integrative treatment of coronary heart disease with premature ventricular contractions and published in the last decade; major type of interventions for medical treatment in the control group plus Integrative therapy, the control group for Western conventional RCTs of the foundation treatment, whether blinded.②Exclusion criteria: non-clinical study of literature or case reports; class clinical research of the purely Chinese Medicine and Western Medicine published literatures or translation of foreign literatures; literature research has nothing to do with the human coronary heart disease with premature ventricular contractions or report serious complications; the duplicated literatures.③Systematic reviews: we checked the retrieved literatures by reading the article title and the abstract, and then scored the selected text by modified Jadad quality scorecard following reading the whole content (1-3points as low quality,4-7points considered high quality). The literatures Incorporated into our study must be more than2scores by modified Jadad quality scorecard. Finally, we systematic reviewed the RCTs by the homemade system evaluation information collection form according to the22common international standard of the CONSORT statement combined with the quality of life evaluation principle of the Cochrane.④Meta analysis: we evaluated the quality of the included studies according to the quality evaluation criteria recommended by the Cochrane Systematic Review’s manual. All four quality evaluation criteria completely satisfied rated class A; if one or more of inadequate or non-implementation rated class B; If any one or more of the quality evaluation criteria which completely unsatisfied rated C class. Meanwhile, the RCTs were scored by modified Jadad quality scorecard and then analyzed using RevMan5.1Software. The total Jadad score is7and above4is considered as high quality research. Weighted mean difference (WMD) was used when the continuous variables were the same units of measurement, while relative risk degree (RR) for categorical variables using. Both effects of volume were presented with95%CI, P<0.05was statistically significant different. Results:(1) Bibliometric analysis of the literatures:①Annual amount: we found that the number of published literature generally presents a rising trend through analyzing the seized literature. the literature published in2000accounted for4.2%of the total number during the next decade, while that in2009accounted for18.1%.②The distribution of published journals and authors:the literatures were more common in Integrative Medicine journal of cardiovascular and cerebro-vascular disease, modern Chinese and Western Medicine, Practical Traditional Chinese Internal Medicine, Journal of Emergency in Traditional Chinese Medicine, Traditional Chinese Medicine, Inner Mongolia journals and so on. The papers published in core journals only accounting for14.6%of the total amount of literature. The authors were from most provinces across our country, but relatively concentrated in the Northeast, East Asia, the western region is more scarce.③The distribution of the type of clinical research: the clinical researches mainly focused in the area of prevention methods, accounting for90.9%of the total amount of literature. The amount of nursing research was more than other types. These results indicate that there is a great potential and advantages of Traditional Chinese Medicine and Integrative Medicine for the prevention and treatment of coronary heart disease with premature ventricular contractions.④The distribution of TCM syndrome type: there were more than70syndrome types in our seized literature. For the same syndrome type of TCM, there was no unified standardized criteria. Among them, the qi and yin deficiency, heart collateral stasis both are the most common types.(2) RCTs systematic review:①The Jadad evaluation results:309selected clinical treatment literature of Integrative Medicine on coronary heart disease with premature ventricular contractions have scored using modified Jadad scale scoring evaluation.30RCTs literature scored2points and8scored more than3points.②The CONSORT evaluation results:30articles scored more than2points were included in the systematic review. The total number of cases reached to2991, while1657patients received Integrative treatment of coronary heart disease with premature ventricular contractions. All30articles have referred to the "random" grouping, All30articles have referred to the "random" grouping,7articles using completely random method,19using a simple random method, the remaining four only mentioned "random" and the specific method was unknown.11of30articles mentioned blinded,7articles confessed to "double-blind",4confessed as "single-blind", the rest did not mention whether blinded. Only4of30articles reported the withdrawal and2of30cases reported lost to the recording. Therefore, all30reports are low quality methodology literature.③Statistical analysis:the statistical methods in26of all30articles are reasonable, the other four did not confess to using any statistical methods.13of30articles recorded complete data, while other17only recorded part.④The evaluation of research results:All30articles took into account the statistical and clinical significance simultaneously. The better relevance and feasibility of the design program accounted for86.7%. The test effects assessed with a good degree of standardization was less than1/3. The better promotion of test results accounted for56.4%. Only two articles mentioned patients’ quality of life " after treatment with Integrative Medicine.(3) RCTs Meta-analysis:①Quality evaluation of included RCTs:1RCT was for class A, while7for class B.②The efficacy of premature ventricular contractions:7studies were included into Meta-analysis. Since their treatment were different treatment, subgroup analysis was used. Shensongyangxin Capsules were more effective than mexiletine (RR=1.39,95%CI [1.14,1.69],P=0.001), while compared with amiodarone there was no significant difference (RR=0.98,95%CI [0.85,1.12], P=0.750) between the two groups. The efficiency in Shensongyangxin capsules group was higher than that in matrine group (RR=1.37,95%CI [1.18,1.69], P<0.001). The Fulvbaoxinping oral solution was more effective than wenxin particle (RR=1.48,95%CI [1.21,1.80], P<0.001). The Wenjiheji was better than Wenxin particle combined with Soothing pill (RR=1.42,95%CI [1.06,1.91], P=0.020).③The efficiency in TCM Syndrome:Four RCTs have been studied. Shensongyangxin Capsules were more effective than mexiletine (RR=1.34,95%CI [1.21,1.49], P<0.001); Fumai particle group is superior to mexiletine group (RR=2.17,95%CI [1.37,3.43], P=0.001).④ECG efficacy: Six RCTs have been included into analysis. Shensongyangxin Capsules were more effective than mexiletine (RR=1.48,95%CI [1.15,1.90], P=0.002). The Fulvbaoxinping oral solution was more effective than wenxin particle (RR=1.39,95%CI [1.00,1.94], P<0.05). The Wenjiheji was better than Wenxin particle combined with Soothing pill (RR=2.08,95%CI [1.31,3.32], P=0.002). There was no significant difference between Fumai particle group and mexiletine group (RR=0.93,95%CI [0.76,1.13], P=0.450).⑤Adverse reactions:8studies reported adverse events or safety indicators.Conclusion:(1) There is great potential in the treatment of coronary heart disease associated with premature ventricular contractions by Traditional Chinese Medicine/Integrative Medicine, but in many respects, it still needs further study.(2) The quality of clinical research study on the treatment of coronary heart disease associated with premature ventricular contractions by Integrative Medicine is low in methodology. The randomization and blind is seldom used, so the credibility of the results is not high. It needs more rigorous trial design.(3) The Meta-analysis of RCTs in the combination therapy of coronary heart disease with premature ventricular contractions shows that the treatment using traditional Chinese medicine and Integrative Medicine program is significantly more effective than Western medicine alone.Part II:The randomized controlled trials for treating coronary heart disease patients with premature ventricular contractionsObjective:(1) The main purpose:To confirm the exact effect of the different treatment programs in clinical practice through a random, double-blinded, controlled clinical trials on the treatment of coronary heart disease associated with premature ventricular contractions by Integrative Medicine.(2) The secondary purpose:①To analyze the incidence and developed trends of coronary heart disease associated with premature ventricular contractions and its characteristics of TCM types;②To select the optimization program of the medication in Integrative Medicine.Method:(1) experimental design:multi-center, randomized, double-blind, parallel, controlled clinical trials.(2) Trial Centers:Traditional Chinese Medicine Hospital of Guangzhou City, Traditional Chinese Medicine Hospital of Huangpu District, Traditional Chinese Medicine Hospital of Shanxi Province, the Second People’s Hospital of Nanchang City, the Second People’s Hospital of Dongyang City.(3) The study population: The included case must meet the inclusion criteria and not meet the exclusion criteria.(4) Sample size: The sample size has been estimated according to the efficiency of primary indicators. Based on the reports and our pre-experimental results, it is assumed that the overall treatment efficiency of amiodarone is73%, that of Dingxin Recipe is80%, and that of Dingxin Recipe plus amiodarone is90%. a=0.05, test performance=80%,102cases in each group were required using nQuery Advisor7.0software. To consider shedding culling rate of about20%, there were120cases required in each group and total number is360.(5) The test groups:control group (amiodarone group), test group1(Dingxin Recipe group), and group2(Dingxin Recipe+amiodarone group).(6) Blinded:double-blind and double-dummy.(7) Randomization:The layered sections randomized was used with SAS9.2software.(8) Treatment programs:Dingxin Recipe group: Dingxin Recipe was given to patients twice a day for four weeks. The amiodarone group:amiodarone hydrochloride tablets, each0.2g, was given orally3times a day; After one week, it was took2times a day; After two weeks, it was given to patients once a day to maintain its efficacy till four weeks. Dingxin Recipe+amiodarone group:the amiodarone medication was the same as above. Half an hour after amiodarone Dingxin Recipe were took.(9) The efficacy of indicators:①The primary efficacy indicator: the efficiency of premature ventricular contractions;②secondary outcome measures:TCM syndromes, heart rate variability analysis.(10) Statistical analysis:Both the primary and secondary efficacy indicators were analyzed by difference test, meanwhile taking into account the effect of the center. The level variables were analyzed using the Kruskal-Wallis H test, while qualitative variables using Pearson χ2. When considering other factors using binary logistic regression.Results:(1) Completion of cases: There were17cases removed in all360cases included in our clinical trial. The left343cases completed the trial. There were357cases in MITT,343cases in PP, and358cases in SAP.(2) Compliance: All subjects had no mismatch with bad records.(3) Describe and compare demographic and clinical data: There were no statistically differences in three groups of cases of gender (χ2=0.024, P=0.988), age (F=0.166, P=0.847), duration (F=0.283, P=0.754) and premature ventricular contractions classification situation (P=0.739).(4) The effectiveness of evaluation:①Primary efficacy indicator: The efficiency of premature ventricular contractions in three groups was statistically different (P=0.001) and the effectiveness of them is respectively72.3%(control group),73.9%(test group1) and90.7%(test group2). Compared to control group and test group1, the efficacy in test group2was much higher and the difference was statistically significant (P=0.001). After the correction center, the efficiency in the three groups was statistically different (P<0.001). The results by PP analysis and MITT analysis results are basically coincidence.②Secondary efficacy evaluation: TCM syndromes:The efficiency of TCM syndromes in three groups was statistically different (P<0.001). After center correction with logistic regression, three sets of efficiency difference was statistically significant (P=0.004), and at the same time there was the center effect. The analysis results with PP and MITT are basically coincidence. ECG efficacy: The efficiency of ECG efficacy in three groups was not statistically different (P=0.772). After center correction with logistic regression, the difference in the three groups was statistically significant (P=0.043). The results by PP and MITT analysis are basically the same. Palpitations score: The efficiency of palpitations score in three groups was statistically different (P=0.015). After center correction using logistic regression, the three groups showed no significant difference (P=0.145). In a word, the efficiency of premature ventricular contractions as well as TCM syndromes in test group2is superior than that in test group1and control group.Conclusion:(1) This clinical program is based on evidence-based medicine, according to the multi-center, large sample, randomized, controlled, double-blind trial design principles. The trial is executed in seven hospitals in four provinces.360patients with coronary heart disease associated with premature ventricular contractions have been included in the trial after informed consent.(2) The gender, age, duration of the three groups of patients and premature ventricular contractions grading are not statistically different through analysis of demographic and clinical data. The consistency of baseline level is better.(3) The Integrative treatment program is much superior to the Chinese herb or Western medicine only in both the efficiency of premature ventricular contractions and TCM syndromes. It confirms that the Integrative treatment program on coronary heart disease associated with premature ventricular contractions is much effective and inexpensive and less toxicity. It is worthy of further clinical promotion. |
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