+Model YCTIM-1413; No. of Pages 11
ARTICLE IN PRESS
Complementary Therapies in Medicine (2015) xxx, xxx—xxx
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevierhealth.com/journals/ctim
Wen Dan Decoction for hemorrhagic stroke and ischemic stroke Jia-Hua Xu a,b,1, Yan-Mei Huang a,1, Wei Ling a, Yang Li c, Min Wang a, Xiang-Yan Chen d, Yi Sui e, Hai-Lu Zhao a,∗ a
Center for Diabetic Systems Medicine, Guangxi Key Laboratory of Excellence, Guilin Medical University, Guilin 541004, China b Fangchenggang Hospital of Traditional Chinese Medicine, Guangxi 538021, China c Department of Gastroenterology, Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, China d Division of Neurology, Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong Special Administrative Region e Department of Endocrinology, Guangdong Hospital of Traditional Chinese Medicine, Guangzhou 510120, China
KEYWORDS Wen Dan Decoction; Chinese herbal medicine; Traditional Chinese medicine; Ischemic stroke; Hemorrhagic stroke; Systematic review; Meta-analysis; Meta-regression analysis
∗ 1
Summary Objective: The use of traditional Chinese medicine (TCM) in stroke is increasing worldwide. Here we report the existing clinical evidence of the Pinellia Ternata containing formula Wen Dan Decoction (WDD) for the treatment of ischemic stroke and hemorrhagic stroke. Methods: PubMed, CNKI, Wan Fang database, Cochrane Library and online Clinical Trial Registry were searched up to 26 February 2013 for randomized, controlled clinical trials (RCTs) using WDD as intervention versus Western conventional medicine as control to treat stroke. Clinical outcomes were improvement of the Neurological Functional Deficit Scores (NFDS) and overall therapeutic efficacy rates including rate of cure. Meta-regression analysis using Hedges’g was performed for RCTs with significant heterogeneity. Results: A total of 22 RCTs of ischemic stroke and 4 RCTs of hemorrhagic stroke, involving 2214 patients (1167 used WDD), met our inclusion criteria. Meta-analysis of the 13 RCTs reporting NFDS improvement favored WDD over the control (mean difference = −3.40, 95% confidence intervals [CI] = [−4.64, −2.15]). Rate of overall therapeutic efficacy (odds ratio [OR] = 3.39, 95%CI = [1.81, 6.37]) for hemorrhagic stroke were significantly higher in WDD treated patients than the control subjects. In the 1898 patients with ischemic stroke, WDD medication also achieved higher rates of cure (OR = 2.22, 95%CI = [1.66, 2.97]) and overall therapeutic efficacy (OR = 3.31, 95%CI = [2.54, 4.31]) than the conventional treatment.
Corresponding author. Tel.: +86 0773 5805803; fax: +86 0773 5895805. E-mail address: [email protected] (H.-L. Zhao). These authors contributed equally to this work.
http://dx.doi.org/10.1016/j.ctim.2015.01.001 0965-2299/© 2015 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Xu J-H, et al. Wen Dan Decoction for hemorrhagic stroke and ischemic stroke. Complement Ther Med (2015), http://dx.doi.org/10.1016/j.ctim.2015.01.001
+Model YCTIM-1413; No. of Pages 11
ARTICLE IN PRESS
2
J.-H. Xu et al. Conclusions: WDD displays benefits on improvement of neurological function and overall therapeutic efficacy in post-stroke patients. TCM such as WDD may serve as a therapeutic tool of dual actions to explore the common mechanisms underlying cerebral hemorrhage and ischemia. © 2015 Elsevier Ltd. All rights reserved.
Contents Introduction............................................................................................................... Methods ................................................................................................................... Eligibility criteria..................................................................................................... Types of studies and participants .............................................................................. Types of interventions ......................................................................................... Types of outcome measures.................................................................................... Data sources and search ....................................................................................... Study selection and data collection process.................................................................... Quality assessment ............................................................................................ Synthesis of results ............................................................................................ Results .................................................................................................................... Study characteristics ................................................................................................. Risk of bias within studies ............................................................................................ Synthesis of results ................................................................................................... Improvement of neurologic functional deficit score ............................................................ The therapeutic efficacy rates for hemorrhagic stroke ......................................................... The therapeutic efficacy rates for ischemic stroke ............................................................. The therapeutic efficacy rates for both ischemic stroke and hemorrhagic stroke............................... Discussion ................................................................................................................. Conflict of interests ....................................................................................................... Acknowledgments ......................................................................................................... Appendix A. Supplementary data........................................................................................ References ................................................................................................................
Introduction
Methods
Traditional Chinese medicine (TCM) has long been used for maintaining health sustained by dynamic homeostasis.1 According to TCM theory, the living homeostasis depends on the dynamic balance of the dual Yin-Yang forces. The dual forces manifest as hypo-function versus hyperfunction. For example, hypotension—hypertension and ischemia-hemorrhage represent the duality of hemodynamic disorders. Western medicine usually relies on different approaches for ischemic stroke and hemorrhagic stroke. In contrast, many specific TCM formula and even single TCM herb can have dual actions like the feeling of happiness—sadness by drinking a same bottle of Chinese liquor. One of the most commonly prescribed formulae for both ischemic stroke and hemorrhagic stroke is Wen Dan Decoction (WDD). WDD, documented as early as 652 AD (Tang Dynasty), is one of classic TCM prescription for patients’ recovery from critical illness. The WDD formula comprises of Banxia (Pinellia ternata), Shengjiang (Ginger), Zhuru (Bamboo shavings), Zhishi (Unripe bitter orange), Chenpi (Tangerine peel) and Gancao (Licorice root). All the six herbs are recorded in the Chinese Pharmacopeia. Papers reporting clinical studies of WDD have often been published in Chinese journals which are not widely read and not highly understood. Hereby we present the existing clinical evidence of WDD for ischemic stroke and hemorrhagic stroke.
Eligibility criteria
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
Types of studies and participants Randomized controlled clinical trials (RCTs) that evaluated the efficacy of WDD for patients with either ischemic stroke, hemorrhagic stroke or both (i.e. mixed ischemic and hemorrhagic stroke). Clinical diagnosis of stroke met at least one of the following criteria: (1) sudden weakness or numbness of the face, arm or leg, with difficulty walking, speaking and understanding, caused by the interruption of the blood supply to the brain; (2) the World Health Organization (WHO) definition2 ; and (3) the Diagnostic Criteria issued at the Second and Revised at the Fourth National Cerebrovascular Diseases Conference in China.3 The interruption of the blood supply to the brain was evident by computed tomography (CT) scan or magnetic resonance imaging (MRI). There were no restrictions on patients’ gender and age. Types of interventions The patients of the control group were given Western conventional medicines (WCM) alone, while patients in the treatment groups received WDD therapy. The dosage of WDD ingredient herbs were as follows: Banxia 10—15 g,
Please cite this article in press as: Xu J-H, et al. Wen Dan Decoction for hemorrhagic stroke and ischemic stroke. Complement Ther Med (2015), http://dx.doi.org/10.1016/j.ctim.2015.01.001
+Model YCTIM-1413; No. of Pages 11
ARTICLE IN PRESS
Chinese herbal medicine for stroke Shengjiang 6—15 g, Zhuru 10—15 g, Zhishi 10—15 g, Chenpi 9—15 g, and Gancao 6—10 g. Types of outcome measures Clinical outcomes were the scores of neurological improvement and the efficacy rates. Here we adopted the Modified Edinburgh-Scandinavian Stroke Scale (MESSS) as the criteria of Neurological Functional Deficit Score (NFDS). MESSS is a nationwide accepted scoring system including consciousness, gaze, facial paresis, language, walking ability, motor function of arms, legs, and hands. In accordance with the MESSS, the efficacy rates of WDD included rates of cure (NFDS decreased up to 91—100%, and disability degree was at grade 0), efficiency (NFDS decreased to 46—90%, and disability degree was grade 1—3), and improvement (NFDS decreased to 18—45%).4 Data sources and search We searched up to 26 February 2013 the PubMed, Wanfang database, Chinese National Knowledge Infrastructure (CNKI), Cochrane Library and online Clinical Trial Registry. The search terms used were ‘‘wendan decoction’’ and ‘‘Stroke’’. We also searched available conference proceedings for potential studies. The reference lists of all relevant articles were checked for any additional studies. Study selection and data collection process All articles were read by two independent reviewers (Wei LING, Yan-Mei HUANG), who archived data from the articles according to a standardized data extraction form, including patients, methods, interventions, and outcomes. For eligible studies, the two reviewers extracted outcome data independently. Disagreements were resolved through consultation with third party authors (Hai-Lu ZHAO and Yang LI). Quality assessment The quality assessment of the included RCTs was evaluated using the Jadad score.5 The final score ranged from 0 to 5 points, with higher scores indicating better reporting. Studies with a Jadad score of 2 or less were considered to have low quality and those with a Jadad score of 3 or more were considered to have high quality.6 Synthesis of results The efficacy rates and NFDS were evaluated by odds ratios (OR) with 95% confidence intervals (CI). Improvement in neurological functional deficit was assessed by single effect size of a mean difference (MD) and a standardized MD (SMD), while Hedges’g was used as the effect size to correct for bias associated with small sample sizes and heterogeneity.7 Pooled effect sizes with 95% CI were calculated using a fixed or random effect model. Meta-regression was used for significant heterogeneity. Evidence of heterogeneity was examined with Cochran’s I2 -test and tau2 . For outcomes with I2 values of 50% or more were considered to be indicators of a substantial level of heterogeneity, we conducted meta-regression statistic model to determine if the a priori covariates (for publication year, course of disease and treatment duration)
3 84 of records identified through database searching
none of additional records identified
84 of records screened on title and abstract
58 of records excluded -30 studies were not clinical trials -12 studies were case reports -14 studies lack of control group -2 studies were duplicate publications
26 of studies included in meta-analysis
Figure 1 cess.
Flowchart of the included studies’ selection pro-
of TCM formulation yielded differing effects. Also, data were further stratified into subgroups to maximize the similarities among studies. Finally, publication bias was quantified using Begg’s and Egger’s test.8 A two-tailed P > 0.05 was considered to be no bias. All these analyses were performed using the Cochrane RevMan 5.1 program, followed by confirmation with the Stata 11.0. Risk of bias was assessed using Cochrane Review guidelines.9
Results Study characteristics Initially we identified 84 potentially relevant articles (Fig. 1). Among them, 58 articles were not met the inclusion criteria and consequently excluded. Finally, 26 studies,10—35 involving a total of 2214 participants (1167 used WDD), met our inclusion criteria. All the 26 studies were conducted in China and published in Chinese journals between 1999 and 2012. Diagnosis of stroke in the 26 RCTs relied on both clinical examination and CT/MRI assessment. Among the 2214 patients, 2053 individuals had ischemic stroke, 155 hemorrhagic stroke, and 6 mixed ischemic and hemorrhagic stroke. The duration of post-stroke intervention varied from 14 days to 30 days. Characteristics of the 26 RCTs are summarized in Table 1.
Risk of bias within studies All studies were described as randomized, but only 3 articles had reported details of random sequence generation14,21,22 and none of the studies mentioned allocation concealment or information about blinding. Only one study showed dropout data.30 The Jadad score of the four articles was 2 points,13,18,19,30 contrasting 1 point in the others. In general, all 26 RCTs showed an unclear risk of bias based on the Cochrane Risk of Bias tool. Table 2 shows the methodological quality of the included 26 RCTs.
Please cite this article in press as: Xu J-H, et al. Wen Dan Decoction for hemorrhagic stroke and ischemic stroke. Complement Ther Med (2015), http://dx.doi.org/10.1016/j.ctim.2015.01.001
First author year
Sample size
Total effective
Total Ischemic effective stroke patient
Treatment/ control
Treatment group
Control group
Hemorrhagic Ischemic and stroke hemorrhagic patient stroke patient
Intervention
Trial group
Control group
Main outcome measure
Course of Course of disease treatment (d) (d)
26 38
24 34
60 78
0 0
0 0
WDD WDD
WCM WCM
TER, NDS TER
Chen 2009 Chen2007 Ding2006 Gao2004
45/45 30/30 40/38 32/31
40 29 36 30
33 24 27 25
90 60 78 63
0 0 0 0
0 0 0 0
WDD WDD WDD WDD
WCM WCM WCM WCM
TER TER, NDS NDS TER TER
Guo2006 Hu2003 Jiao2012 Li1999 Li2009 Liu2010 Lou2012 Guo2010 Pei1997
24/20 46/45 55/55 60/32 60/56 50/50 45/45 30/30 30/20
16 41 49 50 56 45 45 28 28
12 29 42 20 43 37 40 24 13
44 91 110 92 116 100 90 60 50
0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0
WDD WDD WDD WDD WDD WDD WDD WDD WDD
WCM WCM WCM WCM WCM WCM WCM WCM WCM
TER, TER TER, TER, TER, TER, TER, TER, TER,
Wang2004
50/50
41
32
100
0
0
WDD
WCM
TER
ARTICLE IN PRESS
Complementary Therapies in Medicine (2015) xxx, xxx—xxx
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevierhealth.com/journals/ctim
Wen Dan Decoction for hemorrhagic stroke and ischemic stroke Jia-Hua Xu a,b,1, Yan-Mei Huang a,1, Wei Ling a, Yang Li c, Min Wang a, Xiang-Yan Chen d, Yi Sui e, Hai-Lu Zhao a,∗ a
Center for Diabetic Systems Medicine, Guangxi Key Laboratory of Excellence, Guilin Medical University, Guilin 541004, China b Fangchenggang Hospital of Traditional Chinese Medicine, Guangxi 538021, China c Department of Gastroenterology, Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, China d Division of Neurology, Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong Special Administrative Region e Department of Endocrinology, Guangdong Hospital of Traditional Chinese Medicine, Guangzhou 510120, China
KEYWORDS Wen Dan Decoction; Chinese herbal medicine; Traditional Chinese medicine; Ischemic stroke; Hemorrhagic stroke; Systematic review; Meta-analysis; Meta-regression analysis
∗ 1
Summary Objective: The use of traditional Chinese medicine (TCM) in stroke is increasing worldwide. Here we report the existing clinical evidence of the Pinellia Ternata containing formula Wen Dan Decoction (WDD) for the treatment of ischemic stroke and hemorrhagic stroke. Methods: PubMed, CNKI, Wan Fang database, Cochrane Library and online Clinical Trial Registry were searched up to 26 February 2013 for randomized, controlled clinical trials (RCTs) using WDD as intervention versus Western conventional medicine as control to treat stroke. Clinical outcomes were improvement of the Neurological Functional Deficit Scores (NFDS) and overall therapeutic efficacy rates including rate of cure. Meta-regression analysis using Hedges’g was performed for RCTs with significant heterogeneity. Results: A total of 22 RCTs of ischemic stroke and 4 RCTs of hemorrhagic stroke, involving 2214 patients (1167 used WDD), met our inclusion criteria. Meta-analysis of the 13 RCTs reporting NFDS improvement favored WDD over the control (mean difference = −3.40, 95% confidence intervals [CI] = [−4.64, −2.15]). Rate of overall therapeutic efficacy (odds ratio [OR] = 3.39, 95%CI = [1.81, 6.37]) for hemorrhagic stroke were significantly higher in WDD treated patients than the control subjects. In the 1898 patients with ischemic stroke, WDD medication also achieved higher rates of cure (OR = 2.22, 95%CI = [1.66, 2.97]) and overall therapeutic efficacy (OR = 3.31, 95%CI = [2.54, 4.31]) than the conventional treatment.
Corresponding author. Tel.: +86 0773 5805803; fax: +86 0773 5895805. E-mail address: [email protected] (H.-L. Zhao). These authors contributed equally to this work.
http://dx.doi.org/10.1016/j.ctim.2015.01.001 0965-2299/© 2015 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Xu J-H, et al. Wen Dan Decoction for hemorrhagic stroke and ischemic stroke. Complement Ther Med (2015), http://dx.doi.org/10.1016/j.ctim.2015.01.001
+Model YCTIM-1413; No. of Pages 11
ARTICLE IN PRESS
2
J.-H. Xu et al. Conclusions: WDD displays benefits on improvement of neurological function and overall therapeutic efficacy in post-stroke patients. TCM such as WDD may serve as a therapeutic tool of dual actions to explore the common mechanisms underlying cerebral hemorrhage and ischemia. © 2015 Elsevier Ltd. All rights reserved.
Contents Introduction............................................................................................................... Methods ................................................................................................................... Eligibility criteria..................................................................................................... Types of studies and participants .............................................................................. Types of interventions ......................................................................................... Types of outcome measures.................................................................................... Data sources and search ....................................................................................... Study selection and data collection process.................................................................... Quality assessment ............................................................................................ Synthesis of results ............................................................................................ Results .................................................................................................................... Study characteristics ................................................................................................. Risk of bias within studies ............................................................................................ Synthesis of results ................................................................................................... Improvement of neurologic functional deficit score ............................................................ The therapeutic efficacy rates for hemorrhagic stroke ......................................................... The therapeutic efficacy rates for ischemic stroke ............................................................. The therapeutic efficacy rates for both ischemic stroke and hemorrhagic stroke............................... Discussion ................................................................................................................. Conflict of interests ....................................................................................................... Acknowledgments ......................................................................................................... Appendix A. Supplementary data........................................................................................ References ................................................................................................................
Introduction
Methods
Traditional Chinese medicine (TCM) has long been used for maintaining health sustained by dynamic homeostasis.1 According to TCM theory, the living homeostasis depends on the dynamic balance of the dual Yin-Yang forces. The dual forces manifest as hypo-function versus hyperfunction. For example, hypotension—hypertension and ischemia-hemorrhage represent the duality of hemodynamic disorders. Western medicine usually relies on different approaches for ischemic stroke and hemorrhagic stroke. In contrast, many specific TCM formula and even single TCM herb can have dual actions like the feeling of happiness—sadness by drinking a same bottle of Chinese liquor. One of the most commonly prescribed formulae for both ischemic stroke and hemorrhagic stroke is Wen Dan Decoction (WDD). WDD, documented as early as 652 AD (Tang Dynasty), is one of classic TCM prescription for patients’ recovery from critical illness. The WDD formula comprises of Banxia (Pinellia ternata), Shengjiang (Ginger), Zhuru (Bamboo shavings), Zhishi (Unripe bitter orange), Chenpi (Tangerine peel) and Gancao (Licorice root). All the six herbs are recorded in the Chinese Pharmacopeia. Papers reporting clinical studies of WDD have often been published in Chinese journals which are not widely read and not highly understood. Hereby we present the existing clinical evidence of WDD for ischemic stroke and hemorrhagic stroke.
Eligibility criteria
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
Types of studies and participants Randomized controlled clinical trials (RCTs) that evaluated the efficacy of WDD for patients with either ischemic stroke, hemorrhagic stroke or both (i.e. mixed ischemic and hemorrhagic stroke). Clinical diagnosis of stroke met at least one of the following criteria: (1) sudden weakness or numbness of the face, arm or leg, with difficulty walking, speaking and understanding, caused by the interruption of the blood supply to the brain; (2) the World Health Organization (WHO) definition2 ; and (3) the Diagnostic Criteria issued at the Second and Revised at the Fourth National Cerebrovascular Diseases Conference in China.3 The interruption of the blood supply to the brain was evident by computed tomography (CT) scan or magnetic resonance imaging (MRI). There were no restrictions on patients’ gender and age. Types of interventions The patients of the control group were given Western conventional medicines (WCM) alone, while patients in the treatment groups received WDD therapy. The dosage of WDD ingredient herbs were as follows: Banxia 10—15 g,
Please cite this article in press as: Xu J-H, et al. Wen Dan Decoction for hemorrhagic stroke and ischemic stroke. Complement Ther Med (2015), http://dx.doi.org/10.1016/j.ctim.2015.01.001
+Model YCTIM-1413; No. of Pages 11
ARTICLE IN PRESS
Chinese herbal medicine for stroke Shengjiang 6—15 g, Zhuru 10—15 g, Zhishi 10—15 g, Chenpi 9—15 g, and Gancao 6—10 g. Types of outcome measures Clinical outcomes were the scores of neurological improvement and the efficacy rates. Here we adopted the Modified Edinburgh-Scandinavian Stroke Scale (MESSS) as the criteria of Neurological Functional Deficit Score (NFDS). MESSS is a nationwide accepted scoring system including consciousness, gaze, facial paresis, language, walking ability, motor function of arms, legs, and hands. In accordance with the MESSS, the efficacy rates of WDD included rates of cure (NFDS decreased up to 91—100%, and disability degree was at grade 0), efficiency (NFDS decreased to 46—90%, and disability degree was grade 1—3), and improvement (NFDS decreased to 18—45%).4 Data sources and search We searched up to 26 February 2013 the PubMed, Wanfang database, Chinese National Knowledge Infrastructure (CNKI), Cochrane Library and online Clinical Trial Registry. The search terms used were ‘‘wendan decoction’’ and ‘‘Stroke’’. We also searched available conference proceedings for potential studies. The reference lists of all relevant articles were checked for any additional studies. Study selection and data collection process All articles were read by two independent reviewers (Wei LING, Yan-Mei HUANG), who archived data from the articles according to a standardized data extraction form, including patients, methods, interventions, and outcomes. For eligible studies, the two reviewers extracted outcome data independently. Disagreements were resolved through consultation with third party authors (Hai-Lu ZHAO and Yang LI). Quality assessment The quality assessment of the included RCTs was evaluated using the Jadad score.5 The final score ranged from 0 to 5 points, with higher scores indicating better reporting. Studies with a Jadad score of 2 or less were considered to have low quality and those with a Jadad score of 3 or more were considered to have high quality.6 Synthesis of results The efficacy rates and NFDS were evaluated by odds ratios (OR) with 95% confidence intervals (CI). Improvement in neurological functional deficit was assessed by single effect size of a mean difference (MD) and a standardized MD (SMD), while Hedges’g was used as the effect size to correct for bias associated with small sample sizes and heterogeneity.7 Pooled effect sizes with 95% CI were calculated using a fixed or random effect model. Meta-regression was used for significant heterogeneity. Evidence of heterogeneity was examined with Cochran’s I2 -test and tau2 . For outcomes with I2 values of 50% or more were considered to be indicators of a substantial level of heterogeneity, we conducted meta-regression statistic model to determine if the a priori covariates (for publication year, course of disease and treatment duration)
3 84 of records identified through database searching
none of additional records identified
84 of records screened on title and abstract
58 of records excluded -30 studies were not clinical trials -12 studies were case reports -14 studies lack of control group -2 studies were duplicate publications
26 of studies included in meta-analysis
Figure 1 cess.
Flowchart of the included studies’ selection pro-
of TCM formulation yielded differing effects. Also, data were further stratified into subgroups to maximize the similarities among studies. Finally, publication bias was quantified using Begg’s and Egger’s test.8 A two-tailed P > 0.05 was considered to be no bias. All these analyses were performed using the Cochrane RevMan 5.1 program, followed by confirmation with the Stata 11.0. Risk of bias was assessed using Cochrane Review guidelines.9
Results Study characteristics Initially we identified 84 potentially relevant articles (Fig. 1). Among them, 58 articles were not met the inclusion criteria and consequently excluded. Finally, 26 studies,10—35 involving a total of 2214 participants (1167 used WDD), met our inclusion criteria. All the 26 studies were conducted in China and published in Chinese journals between 1999 and 2012. Diagnosis of stroke in the 26 RCTs relied on both clinical examination and CT/MRI assessment. Among the 2214 patients, 2053 individuals had ischemic stroke, 155 hemorrhagic stroke, and 6 mixed ischemic and hemorrhagic stroke. The duration of post-stroke intervention varied from 14 days to 30 days. Characteristics of the 26 RCTs are summarized in Table 1.
Risk of bias within studies All studies were described as randomized, but only 3 articles had reported details of random sequence generation14,21,22 and none of the studies mentioned allocation concealment or information about blinding. Only one study showed dropout data.30 The Jadad score of the four articles was 2 points,13,18,19,30 contrasting 1 point in the others. In general, all 26 RCTs showed an unclear risk of bias based on the Cochrane Risk of Bias tool. Table 2 shows the methodological quality of the included 26 RCTs.
Please cite this article in press as: Xu J-H, et al. Wen Dan Decoction for hemorrhagic stroke and ischemic stroke. Complement Ther Med (2015), http://dx.doi.org/10.1016/j.ctim.2015.01.001
First author year
Sample size
Total effective
Total Ischemic effective stroke patient
Treatment/ control
Treatment group
Control group
Hemorrhagic Ischemic and stroke hemorrhagic patient stroke patient
Intervention
Trial group
Control group
Main outcome measure
Course of Course of disease treatment (d) (d)
26 38
24 34
60 78
0 0
0 0
WDD WDD
WCM WCM
TER, NDS TER
Chen 2009 Chen2007 Ding2006 Gao2004
45/45 30/30 40/38 32/31
40 29 36 30
33 24 27 25
90 60 78 63
0 0 0 0
0 0 0 0
WDD WDD WDD WDD
WCM WCM WCM WCM
TER TER, NDS NDS TER TER
Guo2006 Hu2003 Jiao2012 Li1999 Li2009 Liu2010 Lou2012 Guo2010 Pei1997
24/20 46/45 55/55 60/32 60/56 50/50 45/45 30/30 30/20
16 41 49 50 56 45 45 28 28
12 29 42 20 43 37 40 24 13
44 91 110 92 116 100 90 60 50
0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0
WDD WDD WDD WDD WDD WDD WDD WDD WDD
WCM WCM WCM WCM WCM WCM WCM WCM WCM
TER, TER TER, TER, TER, TER, TER, TER, TER,
Wang2004
50/50
41
32
100
0
0
WDD
WCM
TER
