title: The efficacy and safety of Chinese herbal medicine, Rhodiola formulation in treating ischemic heart disease: a systematic review and meta-analysis of randomized controlled trials.
abstract: BACKGROUND
  Rhodiola formulation is widely used in treating ischemic heart disease (IHD), angina pectoris in China. A number of clinical studies have reported and claimed that Rhodiola formulation can relieve the symptoms of IHD. This study provides the first Preferred Reporting Items for Systematic Reviews (PRISMA)-compliant systematic review to evaluate the efficacy and safety of Rhodiola formulation in treating ischemic heart disease either as a sole agent or in combination with routine western medicine (RWM).
  
  
  METHODS
  Search strategy - PubMed, Science Direct, the Cochrane Library, China National Knowledge Infrastructure (CNKI), China Master Theses Full-text Database (CMTD), China Doctor Dissertations Full-text Database (CDMD), Wanfang Data (WF) databases were searched for all relevant studies on Rhodiola formulation that have been published in English and Chinese. The last search of all databases was performed on 31 January 2013. All randomized controlled trials (RCTs) of Rhodiola formulation for patients with IHD were included, and the quality of included RCTs was assessed with Cochrane risk of bias tool. The primary outcomes, including the effective size of symptomatic and electrocardiography (ECG) improvement were calculated as an odds ratio (OR) and 95% confidence intervals (CIs). Because of obvious heterogeneity in the studies with regard to herbal species, herbal formulations, treatment group medicines, control group medicines and outcome measurement, subgroup analysis and sensitivity analysis were performed to evaluate the effects of study characteristics of RCTs, including quality, the role of Rhodiola formulations in treatment group and the different control group medicines.
  
  
  RESULTS
  A total of thirteen studies (n=1672) were included. most of included studies were found to be high risk of bias with low quality of methodology. The Rhodiola formulations used alone or in combination with RWM demonstrated a positive effect on both improvement of symptoms and ECG. For the subgroup analysis, the ORs of symptomatic improvement in Rhodiola formulations versus other Chinese herbal medicines (CHMs), Rhodiola formulations versus RWM, and Rhodiola formulations plus RWM versus RWM were 1.51, 2.64, 5.63, respectively. The ORs of symptomatic improvement for Rhodiola formulations versus other CHMs, Rhodiola formulations versus RWM, and Rhodiola formulations plus RWM versus RWM were 1.33, 3.11, 2.27, respectively. Overall, the effectiveness of Rhodiola formulations was higher compared to medicines in control groups, with statistically significant differences observed both in symptomatic improvement (OR=2.40, 95% CI: 1.57-3.66, P<0.0001) and ECG improvement (OR=1.48, 95% CI: 1.17-1.87, P<0.01). However, the sensitivity test indicated that overall effects of Rhodiola formulation versus other CHMs in ECG improvement were not stable (after removing the study by Yin, P=0.05); the differences of CHMs in the control group are a possible source of heterogeneity.
  
  
  CONCLUSIONS
  Rhodiola formulations may have a positive effect on treating IHD alone and in combination with RWM. However, poor quality of methodology and heterogeneity of the included trials means that larger sample size, multi-center, placebo-controlled, double blind studies are needed.
authors.affiliation: Department of Epidemiology, Faculty of Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Graduate Student, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yongjie
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Department of Epidemiology, Faculty of Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Epidemiology, Faculty of Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology, Faculty of Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yaqiong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Epidemiology, Faculty of Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Taiwu
authors.initials: T
authors.lastname: Wang
authors.affiliation: Cardiovascular Disease Research Center, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Epidemiology, Faculty of Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Long
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Epidemiology, Faculty of Preventive Medicine, Third Military Medical University, Chongqing 400038, China. Electronic address: hongyanxiong@126.com.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Xiong
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000453:epidemiology; D016032:Randomized Controlled Trials as Topic; D029771:Rhodiola / Q000737:chemistry*
chemical_list: D004365:Drugs, Chinese Herbal
keywords: Ischemic heart disease; Meta-analysis; Randomized controlled trials; Rhodiola; Systematic review