中医药治疗冠状动脉微血管疾病随机对照试验结局指标的应用研究

Application Analysis of the Outcome Measures in Randomized Controlled Trials of Traditional Chinese Medicine in the Treatment of Coronary Microvascular Disease

背景冠状动脉微血管疾病(CMVD)是目前心血管疾病研究的热点,中医药在治疗CMVD方面有独特优势和显著疗效,但目前相关临床试验研究中存在诊断标准、疗效标准不一致等问题,探索中医药治疗CMVD的核心结局指标集有利于未来形成高质量的循证证据。目的分析中医药干预CMVD随机对照试验中结局指标应用情况,提出对应的问题和建议。方法通过检索中国知网(CNKI)、中国生物医学文献服务系统(SinoMed)、维普网(VIP)、万方数据知识服务平台、PubMed、Embase、Cochrane Library,收集建库至2023-02-09发布的中医药治疗CMVD的随机对照试验。提取研究的基本信息、干预措施、结局指标等,采用Cochrane系统评价手册偏倚风险评估工具对纳入文献进行偏倚风险评价,应用Excel软件对结局指标进行统计分析。结果共纳入88篇文献,其中2篇为临床试验注册方案,1篇为英文文献。Corhrane偏倚风险工具评估结果显示,纳入文献在随机序列生成,分配隐藏,对研究者、受试者实施盲法,对结局评估者实施盲法,其他偏倚方面大多数被评价为不清楚;结局数据的完整性、选择性报告方面大多数被评价为低风险。共18篇文献对纳入的CMVD患者进行中医证候分析,其中包括气虚血瘀证6篇、痰瘀互结证3篇。对结局指标进行统计分析共得到115种结局指标,总频次为571次,可分为临床疗效、理化检测、症状与体征、中医证候积分、生活质量、远期预后、安全性检测7大类,其中临床总疗效率出现的频次最高(46次),3个月为最常用的干预节点,复合结局指标中出现频次最高的为临床疗效结合理化检测(14次)。结论中医药治疗CMVD随机对照试验的质量整体偏低,结局指标存在缺乏规范的中医证候诊断标准和疗效标准、缺乏远期预后监测等问题,未来还需要进行高质量的随机对照试验,结合中医药治疗特色,构建规范的CMVD中医药核心指标集。

Background Coronary microvascular disease(CMVD)is currently a research hotspot in the field of cardiovascular disease,traditional Chinese medicine(TCM)has unique advantages and significant efficacy in the treatment of CMVD,but there are problems in relevant clinical trials,such as inconsistencies in the diagnostic and efficacy criteria,exploring the core outcome set of TCM in the treatment of CMVD is conducive to the development of high-quality evidence in the future.Objective To analyze the application of outcomes measures in randomized controlled trials(RCTs)of CMVD treated with TCM,and propose corresponding questions and recommendations.Methods CNKI,SinoMed,VIP,Wanfang,PubMed,Embase and Cochrane Library were systematically searched for RCTs of CMVD treated with TCM from inception to February 09,2023.The basic information,interventions and outcome measures in RCTs of CMVD treated with TCM were extracted,the Cochrane systematic review manual bias risk assessment tool was used to evaluate the bias risk of the included literature and the Excel software was used to statistically analyze the outcome measures.Results A total of 88 articles were included,involving 2 clinical trial registration protocols and 1 English literature.Cochrane systematic review manual bias risk assessment showed that the included literature were evaluated as unclear in terms of random sequence generation,allocation concealment,blinding of participants and personnel,blinding of outcome assessors,and other bias;mostly low risk in terms of outcome data completeness and selective reporting.A total of 18 RCTs were analyzed for TCM syndromes of patients diagnosed with CMVD,involving 6 RCTs related to blood stasis due to qi deficiency,3 RCTs related to intermingled phlegm and blood stasis.A total of 115 outcome measures were obtained by statistical analysis,the total frequency was 571 times,which can be divided into 7 categories,including clinical efficacy,physicochemical testing,signs and symptoms,TCM syndrome points,quality of life,long-term prognosis,and safety testing.The frequency of total clinical efficacy rate was the highest(46 times),3 months was the most commonly used intervention node.and the highest frequency of composite outcome measures was the clinical efficacy combined with physicochemical testing.Conclusion It was found that the overall quality of RCTs of TCM in the treatment of CMVD was generally low,and there are some problems in the outcome measures,such as the lack of standardized TCM syndrome diagnosis criteria and efficacy criteria,and the lack of long-term prognosis monitoring.In the future,it is also necessary to conduct high-quality RCTs,combined with the characteristics of TCM treatment,to construct a standardized core outcome set of TCM in the treatment of CMVD.