Cochrane Database of Systematic Reviews

Acanthopanax for acute ischaemic stroke (Review)

Li W, Liu M, Feng S, Wu B, Zhang S, Yang W, Liu GJ

Li W, Liu M, Feng S, Wu B, Zhang S, Yang W, Liu GJ.

Acanthopanax for acute ischaemic stroke.
Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No.: CD007032.
DOI: 10.1002/14651858.CD007032.pub2.

www.cochranelibrary.com

Acanthopanax for acute ischaemic stroke (Review)

Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
Analysis 1.1. Comparison 1 Acanthopanax versus control, Outcome 1 Improvement of neurological deficit at the end of
treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

Acanthopanax for acute ischaemic stroke (Review) i

Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
[Intervention Review]

Acanthopanax for acute ischaemic stroke

Weizheng Li1 , Ming Liu1 , Shejun Feng1 , Bo Wu1 , Shihong Zhang1 , Weimin Yang1 , Guan Jian Liu2
1 Department of Neurology, West China Hospital, Sichuan University, Chengdu, China. 2 Chinese Cochrane Centre, Chinese EBM
Centre, West China Hospital, Sichuan University, Chengdu, China

Contact address: Ming Liu, Department of Neurology, West China Hospital, Sichuan University, No. 37, Guo Xue Xiang, Chengdu,
Sichuan Province, 610041, China. wyplmh@hotmail.com.

Editorial group: Cochrane Stroke Group.

Publication status and date: New, published in Issue 3, 2009.
Review content assessed as up-to-date: 19 January 2008.

Citation: Li W, Liu M, Feng S, Wu B, Zhang S, Yang W, Liu GJ. Acanthopanax for acute ischaemic stroke. Cochrane Database of
Systematic Reviews 2009, Issue 3. Art. No.: CD007032. DOI: 10.1002/14651858.CD007032.pub2.

Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

ABSTRACT
Background
Acute ischaemic stroke is a common cause of death and disability. A number of studies published in China have shown that acanthopanax
is beneficial for acute ischaemic stroke.
Objectives
To assess the efficacy and safety of acanthopanax in patients with acute ischaemic stroke.
Search methods
We searched the Cochrane Stroke Group Trials Register (last searched January 2008), the Chinese Stroke Trials Register (last searched
March 2008), and the Trials Register of the Cochrane Complementary Medicine Field (last searched January 2008). In addition, we
searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2008), MEDLINE (1966 to
March 2008), EMBASE (1980 to March 2008), CINAHL (1982 to March 2008), AMED (1985 to March 2008), and nine Chinese
databases, including the China Biological Medicine Database (CBM-disc) (1979 to March 2008). We handsearched three Chinese
journals and searched reference lists, relevant clinical trials registers and research databases. In an attempt to identify further published,
unpublished, and ongoing trials, we contacted a pharmaceutical company, researchers and study authors.
Selection criteria
We included randomised controlled trials comparing acanthopanax with placebo or open control (no placebo) in patients with acute
ischaemic stroke.
Data collection and analysis
Two review authors selected trials for inclusion, assessed trial quality and extracted the data independently.
Main results
We included 13 trials (962 participants); the period of follow up in all included trials ranged from 10 to 30 days. None of the trials
reported the pre-specified primary outcome death or dependency during the follow-up period. The outcome measure in all included
trials was the improvement of neurological deficit after treatment; acanthopanax was associated with a significant increase in the number
of participants whose neurological impairment improved (risk ratio (RR) 1.22, 95% confidence interval (CI) 1.15 to 1.29). Two trials
reported adverse events; five trials reported no adverse events.
Acanthopanax for acute ischaemic stroke (Review) 1
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Authors’ conclusions

The risk of bias in all the included trials was high, and hence the data were not adequate to draw reliable conclusions about the efficacy
of acanthopanax in acute stroke. Much larger trials of greater methodological quality are needed.

PLAIN LANGUAGE SUMMARY

Acanthopanax for acute ischaemic stroke

Most strokes take place when a blood clot blocks a blood vessel leading to the brain. Without a proper blood supply, the brain quickly
suffers damage, which can be permanent. The damage from a stroke can cause arm or leg weakness, or difficulties with language
or vision. Data from some experimental and human studies have suggested acanthopanax, a traditional Chinese medicine, may be
beneficial for people with acute ischaemic stroke. It has been used in China for many years to treat stroke. To obtain a reliable assessment
of the effects of acanthopanax in acute ischaemic stroke, we reviewed data from 13 studies involving 962 participants. The quality of
the trials was poor, and there was not enough evidence to support the routine use of acanthopanax in the treatment of acute ischaemic
stroke. More high-quality trials are needed.

BACKGROUND thopanax senticosus Harms, has been used as medicine for many
years in China. The leaves of this plant are also used as medicine.
Acute ischaemic stroke carries a high risk of death and disability,
Glycosides, flavonoids, and polysaccharides are the main compo-
which place a burden on patients, family, community and social
nents of acanthopanax. Eleutheroside B (syringin) and eleuthero-
health resources. Optimal treatment for patients suffering from
side E are two major glycosides (Deyama 2001; Fan 2003; Wang
acute ischaemic stroke requires rapid assessment and early inter-
2003). Experimental and human studies have shown that acan-
vention. Although many drug therapies for acute ischaemic stroke
thopanax can be used for dilating the cardiocerebral vessels, sup-
have been studied, only aspirin and thrombolysis with recombi-
pressing the aggregation of platelets, lowering blood viscosity, im-
nant tissue plasminogen activator (rt-PA) remain the approved
proving circulation, increasing superoxide dismutase activity, de-
and validated therapies (Fisher 2000; Sandercock 2003; Wardlaw
creasing oxygen free radicals, protecting against ischaemic reperfu-
2003). Thrombolytic treatment with rt-PA in highly selected pa-
sion injury, and enhancing the tolerance of ischaemic tissue to hy-
tients within three hours of stroke onset has been confirmed to
poxia (Han 1998; Feng 1999; Zhu 1999; Zhang 2000; Lu 2002;
be effective. However, the data do not support the widespread
Du 2003; Feng 2003; Jiang 2004). However, most of the com-
use of thrombolytic therapy in routine clinical practice because
ponents of herbal medicines have not often been specified and
of a high risk of bleeding (Wardlaw 2003). Many other therapies
measured precisely, which is different from industrially manufac-
may have some effect on stroke, and have been shown to be ei-
tured pharmacological drugs used in Western medicine. Although
ther inconclusive or negative. The lack of effective and widely ap-
the Chinese government regulates dosages and the use of these
plicable pharmacological treatments for ischaemic stroke patients
medicines, this inevitably leads to variations between formulations
may explain a growing interest in Chinese traditional medicines,
and batches of the same herbal medicines, which may contribute to
for which extensive observational and anecdotal experience has
any heterogeneity between different study results. Currently there
accumulated over the past one thousand years. In China, tradi-
are some randomised controlled trials (RCTs) of acanthopanax for
tional herbal preparations account for 30% to 50% of the total
acute ischaemic stroke reported in China. One published Chinese
medicinal consumption (WHO 2003). The overall treatment con-
systematic review of acanthopanax injection for acute ischaemic
cept for Chinese traditional medicines is different from Western
stroke (Li 2006) did not follow the methods used for conduct-
medicine, and herbal medicines were always used to treat acute
ing a Cochrane systematic review. It showed that acanthopanax
ischaemic stroke. Acanthopanax is one of the most widely used
injection is effective for acute ischaemic stroke, but the evidence
Chinese herbal medicines.
is not strong due to the generally low methodological quality of
the included trials. It is uncertain whether the existing evidence is
of sufficient scientific rigor to recommend acanthopanax for rou-
Acanthopanax, the root and stem bark of the Araliaceae plant Acan-
Acanthopanax for acute ischaemic stroke (Review) 2
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
tine treatment. We therefore planned to perform a systematic re-
view based on evidence from randomised controlled trials of acan-
thopanax for acute ischaemic stroke to provide the best available
evidence for clinical practice.
OBJECTIVES
To assess the efficacy and safety of acanthopanax in patients with
acute ischaemic stroke.
METHODS
Criteria for considering studies for this review
Types of studies
We included RCTs comparing acanthopanax with placebo or open
control (no placebo) in patients with acute ischaemic stroke. We
excluded confounded trials in which the treatment or control
group received another active therapy (for example, acanthopanax
versus another drug).
Types of participants
Trials involving patients of any age or sex with acute ischaemic
stroke (within 14 days of onset) were eligible. Ischaemic stroke was
defined according to the criteria of the World Health Organization
(WHO 2003), with computerised tomography (CT) or magnetic
resonance imaging (MRI) to exclude haemorrhagic stroke.
Types of interventions
We included trials evaluating acanthopanax regardless of dosage,
duration and route of administration. The control interventions
were placebo or no treatment. We included trials where the addi-
tion of acanthopanax to another treatment was compared with the
other treatment alone and the trial was therefore assessing acan-
thopanax.
Types of outcome measures
1. Death or dependency at the end of scheduled follow up.
Dependency was defined as dependent on others in activities of
daily living, e.g. Barthel Index scored 60 or less, or modified
Rankin Scale graded 3 to 5 (Sulter 1999).
2. Death from all causes within the first two weeks of
treatment, and during the whole follow-up period.
3. The proportion of patients with marked neurological
improvement after treatment. The measures could focus on
Acanthopanax for acute ischaemic stroke (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
specific impairment (e.g. motor deficit, cognitive impairment) or
global neurological deficit (such as the National Institute of
Health Stroke Scale, the Canadian Neurological Scale, the
European Stroke Scale, the Scandinavian Stroke Scale, or the
Clinical Neurological Impairment Score Criteria of Stroke
Patients revised by the fourth Nationwide Conference of
Cerebrovascular Disease).
4. Quality of life if assessed by the included trials.
5. Expected adverse events, such as new stroke or myocardial
infarction.
6. Unexpected adverse events, such as allergic reaction,
bleeding, nausea, vomiting, tachycardia, or other serious adverse
events caused by acanthopanax. The number of patients
developing at least one adverse event listed above was evaluated.
Search methods for identification of studies
See the ’Specialized register’ section in the Cochrane Stroke Group
module.
We searched the Cochrane Stroke Group Trials Register, which was
last searched by the Review Group Co-ordinator in January 2008,
the Chinese Stroke Trials Register (last searched in March 2008),
and the trials register of the Cochrane Complementary Medicine
Field (last searched in January 2008). In addition, we searched
the Cochrane Central Register of Controlled Trials (CENTRAL)
(The Cochrane Library Issue 1, 2008), MEDLINE (1966 to March
2008) (Appendix 1), EMBASE (1980 to March 2008), CINAHL
(1982 to March 2008), The Allied and Complementary Medicine
Database (AMED) (1985 to March 2008) and the China Biologi-
cal Medicine Database (CBM-disc) (1979 to March 2008), which
is a database of Chinese biomedical research literature.
We searched the Chinese Cochrane Centre Controlled Trials Reg-
ister (last searched in March 2008), China National Knowledge In-
frastructure (CNKI) (1979 to March 2008), Chinese MD and DD
Dissertations in CNKI (1999 to March 2008), the Chinese sci-
entific periodical database of VIP INFORMATION (VIP) (1989
to March 2008), the Chinese Evidence-Based Medicine Database
(last searched in March 2008), the Chinese Academic Conference
Papers Database (CACP) (1986 to March 2008), the Chinese Dis-
sertations database (CDDB) (1977 to March 2008), and the Wan-
fang Database (1979 to March 2008).
We handsearched the following three Chinese journals (from the
first year of publication):
• Chinese Journal of Information on Traditional Chinese
Medicine (1994 to January 2008);
• Chinese Traditional Patent Medicine (1978 to January 2008);
• Journal of Emergency in Traditional Chinese Medicine (1992
to January 2008).
In January 2008, we also searched relevant clinical trials and re-
search databases, including the Stroke Trials Directory (http://
www.strokecenter.org/trials/), the National Center for Comple-
3
mentary and Alternative Medicine (http://www.nccam.nih.gov/
clinicaltrials/), the National Institute of Health Clinical Trials
Database (http://www.clinicaltrials.gov/) and HERBMED (http:
//www.herbmed.org).
Additionally, we searched the reference lists of relevant trials and
contacted colleagues and researchers to identify published, un-
published and ongoing studies. At the same time, we contacted
the pharmaceutical company manufacturing acanthopanax (Hei-
longjiang Wandashan Pharmaceutical Co Ltd) and some study
authors for additional data but we did not receive any response.
Data collection and analysis
Study selection
According to a prespecified protocol, two review authors checked
the titles, abstracts, and full text articles identified by the searches,
and selected trials for inclusion. We resolved any disagreements
through discussion or with a third review author if necessary.
Quality assessment
We assessed methodological quality according to the following
internal validity criteria:
1. randomisation (RCTs only);
2. adequate allocation concealment (these items will be
assessed according to The Cochrane Collaboration’s standard
criteria: grade A - adequate; grade B - unclear; grade C -
inadequate);
3. blinding: blinding of investigator, participants, outcome
assessor;
4. intention-to-treat analysis;
5. number lost to follow up.
Two review authors independently performed quality assessment,
and we resolved any disagreements through discussion or with a
third review author if necessary.
Data extraction
Two review authors independently extracted data on participants,
methods, interventions, outcomes, and results, and recorded this
information on a data extraction form. If necessary, we contacted
study authors for missing data.
Data analysis
We compared acanthopanax with placebo, acanthopanax with no
placebo, and acanthopanax plus other care with other care alone.
We presented results as risk ratio (RR) with 95% confidence inter-
val (CI) for dichotomous outcomes, and mean difference (MD) or
standardised mean difference (SMD) and 95% CI for continuous
Acanthopanax for acute ischaemic stroke (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
outcomes, using a fixed-effect model if no substantial statistical
heterogeneity was present. Otherwise we used a random-effects
statistical model. We assessed heterogeneity using the I2 statistic,
with a value greater than 50% indicating substantial heterogene-
ity. If we identified sufficient trials, we planned to test potential
publication bias using a funnel plot.
We planned to perform sensitivity analyses by excluding:
(1) trials with inadequate allocation concealment or blinding or
no placebo;
(2) unpublished studies (if there are any).
RESULTS
Description of studies
See: Characteristics of included studies; Characteristics of excluded
studies.
We identified 795 references through electronic searches and hand-
searches. We identified 27 potentially eligible trials after exclud-
ing 768 irrelevant references, and included 13 trials in the re-
view (He 1998; Jia 1998; Long 2000; Wu 2000; Qin 2001; Yu
2002; Ye 2003; Xu 2003; Wen 2005; Peng 2006; Wang 2006; Li
2007; Xiao 2007). Summary details of these trials are given in the
’Characteristics of included studies’ table. Of the 27 potentially
eligible trials identified, we excluded three trials (Du 2003; Du
2004a; Du 2004b) that were published in different journals, which
included the same participants with different blood examination
indexes; no usable data were available for analysis in these studies.
We excluded nine trials (Fan 2000; Hu 2000; Dong 2001; Wu
2002; Jiang 2003; Zhou 2003; Zhang 2005; Wang 2005; Zhou
2006) because they were not randomised trials. We excluded one
trial (Cai 2005) because the stage of stroke was not reported, and
excluded another trial (Kuang 2001) because the interventions in
both groups were unclear, so we could not establish if the trial met
the inclusion criteria for the types of interventions.
All 13 of the included studies are published in Chinese and have
a total of 962 participants. Eleven studies (He 1998; Jia 1998;
Long 2000; Wu 2000; Qin 2001; Yu 2002; Ye 2003; Xu 2003;
Wen 2005; Li 2007; Xiao 2007) reported the average age of the
participants, which ranged from 58 to 66.7 years. Another two
studies (Peng 2006; Wang 2006) only reported the interval of age
in participants. All 13 trials reported the inclusion criteria, and five
trials (Long 2000; Xu 2003, Wen 2005; Peng 2006; Xiao 2007)
described the exclusion criteria. Three trials (He 1998; Wu 2000;
Xu 2003) reported the numbers of participants with severe stroke.
All 13 trials were of acanthopanax plus another treatment com-
pared with the other treatment alone. Acanthopanax injections
ranged from 30 ml to 250 ml per day. The course of treatment
ranged from 10 to 30 days. Only two trials reported the timing
of the start of treatment after stroke onset: the timing in one trial
4
(Yu 2002) was one to three days, and in the other trial (Jia 1998)
was three hours to one week.
Ten trials (He 1998; Wu 2000; Qin 2001; Yu 2002; Xu 2003; Ye
2003; Peng 2006; Wang 2006; Li 2007; Xiao 2007) evaluated the
effect of acanthopanax at the end of treatment on the proportion of
participants with improvement of neurological deficit according to
Modified Edinburgh-Scandinavian Stroke Scale (MESSS). After
reading the studies carefully, we found that five of the 10 trials
(Jia 1998; Long 2000; Wu 2000; Ye 2003; Wen 2005) applied a
measurement of neurological deficit that was similar to MESSS
but defined by the trialists themselves.
Only one trial followed up participants after the end of treatment
(Li 2007): in this trial, the course of treatment was 10 days and
the duration of follow up was 28 days. No deaths were reported
in any of the trials. Only two trials (Long 2000; Li 2007) reported
adverse events. Assessment of quality of life was not undertaken
in any of the trials.
Risk of bias in included studies
One trial (Peng 2006) reported the use of random number tables
to divide the treatment and control groups; the remaining 12 tri-
als reported ’randomly allocating’ participants but the method of
randomisation was not described. None of the 13 trials reported
the method of allocation concealment and so we graded these as
’unclear’ for allocation concealment. None of the trials reported
blinding, so we do not know what method of blinding of partic-
ipants and outcome assessors was used in the trials. The follow-
up period in the included trials was short, and none of the trials
reported drop outs or intention-to-treat analysis. We contacted
study authors for further information about design and method-
ology but received no responses. All the studies stated the baseline
characteristics of the participants were similar between the two
comparison groups.
Effects of interventions
Death or dependency at the end of scheduled follow
up
Assessment of activities of daily living function or any other mea-
sure of disability were not undertaken in any of the included trials.
Death from all causes within the first two weeks of
treatment, and during the whole follow-up period
No deaths were reported within the first two weeks of treatment
or during the whole follow-up period.
Acanthopanax for acute ischaemic stroke (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
The proportion of participants with marked
neurological improvement after treatment
The outcomes measured after treatment were assessed according to
MESSS in eight trials. Meta-analysis of these eight trials that used
a dichotomous outcome variable showed a significantly higher
proportion of participants treated with acanthopanax had an im-
provement of their neurological deficit at the end of treatment
compared with the control participants (RR 1.17, 95% CI 1.10
to 1.25). Five trials used a neurological deficit scale defined by the
trialists, which was similar to the MESSS. There was a significantly
higher proportion of participants with marked neurological im-
provement in the acanthopanax group (RR1.31, 95% CI 1.17 to
1.47). Overall, acanthopanax appeared to increase the proportion
of participants with marked neurological improvement compared
with the control group, and the difference was significant (RR
1.22, 95% CI 1.15 to 1.29).
Quality of life if assessed by the included trials
Assessment of quality of life was not undertaken in any of the
trials.
Expected adverse events, such as new stroke or
myocardial infarction
None of trials reported expected adverse events.
Unexpected adverse events
Seven trials reported unexpected adverse events. Five trials (He
1998; Jia 1998; Wu 2000; Xu 2003; Xiao 2007) clearly reported
that there were no adverse events during the trials. One trial (Long
2000) reported that two participants in the treatment group had
a fever that disappeared after treatment was stopped. No adverse
events were reported in the control group. In another trial (Li
2007), three participants in the treatment group had epistaxis
and gingival bleeding and one participant in the control group
had epistaxis; these phenomena improved after treatment. There
was no difference between the two comparison groups for adverse
events.
A funnel plot analysis showed asymmetry for the outcome measure
about improvement of neurological deficit at the end of treatment.
We could not do sensitivity analyses because none of the trials had
adequate allocation concealment or blinding or used placebo.
DISCUSSION
We included 13 trials involving a total of 962 participants. This
review was done in accordance with the methods of a Cochrane
systematic review, unlike the one previous published review on
acanthopanax for acute ischaemic stroke (Li 2006). We excluded
5
different studies according to the criteria for considering studies,
and identified and included six new trials. There is no clear evi-
dence for the efficacy of acanthopanax for acute ischaemic stroke.
None of the included trials reported the pre-specified primary
outcome of death or dependency defined using the Barthel Index
scale or the Modified Rankin scale during the follow-up period.
The outcome measures used in all trials were at the level of neu-
rological deficit, which were not widely recognised. Most of the
trials did not follow up the participants after treatment; and the
follow-up period was short. Now it has been recommended that
primary outcome measures should be at the level of activity (dis-
ability or dependence), and that outcome assessment should be
undertaken at six months or longer from the start of treatment
(Duncan 2000), because the patients are more concerned with ac-
tivity, and the short follow up cannot assess the long-term effect
of the intervention.
Although three trials (He 1998; Wu 2000; Xu 2003) reported the
numbers of participants with severe stroke, none of the trials re-
ported any deaths. It is possible that only mild strokes were in-
cluded in most trials, or that the authors attempted to empha-
sise the positive role of acanthopanax by not reporting deaths, or
that there were no deaths during the short-term follow-up pe-
riod. The failure of trials to report deaths is a major methodolog-
ical concern. Reports of randomised trials should conform to the
requirements of the CONSORT statement (www.consort-state-
ment.org), which includes reporting all clinically relevant out-
comes, including deaths. It is highly implausible that no deaths
occurred among the 962 included participants.
Moreover, there were many methodological problems in the de-
sign and performance of all the trials. Only one trial (Peng 2006)
reported using a random number table to divide the groups; the
remaining 12 trials reported ’randomly allocating’ participants but
the method of randomisation was not described, and so we could
not be sure if the trials were truly random. None of the 13 trials
reported the method of allocation concealment and were graded as
’unclear’ allocation concealment. None of the trials stated whether
they used a blinded method or intention-to-treat analysis. None of
the included studies reported drop outs. All of this indicates that
the included trials were generally of poor quality. It is this poor
quality that may have led to selection or performance bias, which
resulted in the effect of the intervention being either exaggerated
or minimised. In addition, China publishes unusually high pro-
portions of positive results (Vickers 1998): all the included trials
in this review were conducted in China and published in Chinese.
A funnel plot analysis showed asymmetry for the outcome mea-
sure of improvement of neurological deficit, thus there was also
possible publication bias. Although the estimate of effect on the
secondary outcomes is statistically significant, the observed effects
could also simply be due to bias rather than to a biological effect
of acanthopanax; therefore, the results of the meta-analysis should
be interpreted with caution.
Acanthopanax for acute ischaemic stroke (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
As for adverse events, only seven trials reported adverse events;
there were no differences between the treatment group and the
control group. The remaining six trials did not report any adverse
events during the trial. However, the sample size was small and the
period of follow up was very short, so we do not know if there were
any adverse events in the long-term effect of the intervention.
The efficacy and safety of acanthopanax for acute ischaemic stroke
were strongly influenced by poor quality and weak outcome mea-
sures reported in the included studies of this review. These should
be confirmed by further well-designed randomised controlled tri-
als with widely-applied outcome measures.
AUTHORS’ CONCLUSIONS
Implications for practice
The risk of bias in all included trials was high, and hence the data
were not adequate to draw reliable conclusions about the efficacy
of acanthopanax in acute stroke. The data in this review do not
support the routine use of acanthopanax for treatment of acute
ischaemic stroke.
Implications for research
This review suggests that acanthopanax might improve neurolog-
ical impairment in the treatment of acute ischaemic stroke. How-
ever, since the observed effects may have been due to bias rather
than a true biological effect, further randomised controlled studies
are justified to assess the efficacy and safety of acanthopanax for
patients with acute ischaemic stroke. The design and performance
of future research should consider in particular the use of:
1. appropriate methods of randomisation to generate the
allocation sequence;
2. adequate allocation concealment;
3. blinding of investigator, participants and outcome assessors;
4. use of standard validated outcome measures measured at
some months after randomisation;
5. complete follow up of all randomised participants;
6. reporting of all deaths and adverse events, critically assessed
by standardised monitoring or an effective self-report system.
ACKNOWLEDGEMENTS
We would like to thank Mrs Hazel Fraser for providing relevant
trials from the Cochrane Stroke Group Trials Register and her will-
ingness to answer all our questions related to the review, and Mrs
Brenda Thomas for her help with developing the search strategy
and searching data for us.
6
 REFERENCES
References to studies included in this review
He 1998 {published data only}
He J, Zhang H. Observation on the effect of integrated
traditional and Western medicine for thirty-six patients
with acute cerebral infarction. Chinese Medical of Factory
and Mine 1998;11(1):60–1.
Jia 1998 {published data only}
Jia J, An C. Clinical observation on acanthopanax injection
for thirty-one patients with cerebral infarction. Chinese
Journal of Integrated Traditional and Western Medicine in
Intensive and Critical Care 1998;5(8):368.
Li 2007 {published data only}
Li D, Lu H, Li W. Treatments of acute cerebral infarction
with defibrase and ciwujia. Chinese Journal of Practical
Nervous Diseases 2007;10(3):37–8.
Long 2000 {published data only}
Long M, Long M, Jiang L, Zhang Z. Clinical study on
acanthopanax injection for acute ischaemic cerebrovascular
disease. Chinese Journal of Information on Traditional
Chinese Medicine 2000;7(9):37–8.
Peng 2006 {published data only}
Peng C, Zhong P, Liu H, Mo S. The effect of acanthopanax
injection on thromboxane and prostacyclin in patients with
acute cerebral infarction. Journal of Emergency in Traditional
Chinese Medicine 2006;15(7):732–3.
Qin 2001 {published data only}
Qin P, Zhu W, Liu K, Bu X. Investigation of clinical effect
of ciwujia injection and jiangxianmei combination for acute
cerebral infarction. Chinese Traditional Patent Medicine
2001;23(7):500–2.
Wang 2006 {published data only}
Wang Y, Chen J. The effect of ciwujia injection on
angiotensin-II andendothelin in patients with acute cerebral
infarction. Chinese Journal of Integrative Medicine on Cardio/
Cerebrovascular Disease 2006;4(3):191–2.
Wen 2005 {published data only}
Wen T, Rao P, Zhou L, Guo W. Clinical observation on
acanthopanax injection and hyperbaric oxygen for forty-
three patients with cerebral infarction. Journal of Sichuan of
Traditional Chinese Medicine 2005;23(8):60.
Wu 2000 {published data only}
Wu H, Lu J, Bao C. Clinical observation on acanthopanax
and buflomedil combination for patients with acute cerebral
infarction. Zhejiang Journal of Integrated Traditional Chinese
and Western Medicine 2000;10(8):478.
Xiao 2007 {published data only}
Xiao C, Peng C, Zhong P. The effect of ciwujia injection
on thromboxane and prostacyclin in patients with acute
Acanthopanax for acute ischaemic stroke (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
cerebral infarction. Guangdong Medical Journal 2007;28
(12):2024–5.
Xu 2003 {published data only}
Xu P, Pei H. Clinical effect of acanthopanax injection and
low molecular heparin combination for fifty-six patients
with acute cerebral infarction. China Pharmaceuticals 2003;
12(5):66–7.
Ye 2003 {published data only}
Ye D. Clinical effect of acanthopanax injection for twenty
patients with acute cerebral infarction. Sichuan Medical
Journal 2003;24(10):1101.
Yu 2002 {published data only}
Yu A, Lv L. Treatments of acanthopanax injection for
twenty-eight patients with acute cerebral infarction. China
Pharmaceuticals 2002;11(8):70.
References to studies excluded from this review
Cai 2005 {published data only}
Cai M, Peng X, Luo C, Qin D. Observation on the effect
of acanthopanax injection for post-cerebral infarction
depression. Pharmacology and Clinics of Chinese Materia
Medica 2005;21(2):54–6.
Dong 2001 {published data only}
Dong J. Observation on the effect of acanthopanax for
cerebral infarction. Chinese Journal of Rural Medicine and
Pharmacy 2001;8(7):32.
Du 2003 {published data only}
Du X, Hu C, Liu J, Jia C, Xiang J, Zhong K, et al.The
clinical research on measuring the blood rheology and
ciwujia injection treatment in the acute cerebral infarction.
Chinese Journal of Current Traditional and Western Medicine
2003;1(12):1063–5.
Du 2004a {published data only}
Du X, Jia C, Qin X, Hu C, Liu J, Zhong K, et al.The
clinical research on measuring serum cholesterol indexes and
ciwujia treatment in the acute cerebral infarction. Chinese
Journal of Medicinal Guide 2004;6(6):431–2.
Du 2004b {published data only}
Du X, Hu C, Liu J, Zhu L, Qin X, Jia C, et al.The clinical
research on measuring the inflammation cytokines and
ciwujia treatment in the acute cerebral infarction. Chinese
Journal of Medicinal Guide 2004;6(1):25–7.
Fan 2000 {published data only}
Fan G, Fan G, Zhang L. Observation on the clinical effect
of acanthopanax and troxerutin combination for fifty-three
patients with acute cerebral infarction. Chinese Journal of
Rural Medicine and Pharmacy 2000;7(9):16.
Hu 2000 {published data only}
Hu F, Zhu H. Treatments of acanthopanax injection for
thirty patients with post-stroke depression. Chinese Journal
7
 of Integrated Traditional and Western Medicine 2000;20(8):
629–30.
Jiang 2003 {published data only}
Jiang K, Mao H, Pan H. Clinical observation on Western
medicine basic treatment and acanthopanax injection for
acute cerebral infarction. Chinese Journal of Integrated
Traditional and Western Medicine in Intensive and Critical
Care 2003;10(6):384.
Kuang 2001 {published data only}
Kuang X, Zhang X, Han J. The effect analysis of
acanthopanax for fifty-two patients with cerebral
thrombosis. Chinese Journal of Practical Nervous Diseases
2001;4(3):55–6.
Wang 2005 {published data only}
Wang Z. Clinical analysis of acanthopanax for thirty-two
patients with acute cerebral infarction. Modern Medicine
and Health 2005;21(12):1497.
Wu 2002 {published data only}
Wu Y. Treatments of acanthopanax injection and sodium
ozagrel combination for sixty patients with cerebral
infarction. Hainan Medical Journal 2002;13(11):37.
Zhang 2005 {published data only}
Zhang Y, Tian F. Observation on the effect of acanthopanax
injection for cerebral infarction combined with coma.
Chinese Journal of Rural Medicine and Pharmacy 2005;12
(3):46–7.
Zhou 2003 {published data only}
Zhou Q. Observation on the clinical effect of acanthopanax
injection for 228 patients with cerebrovascular disease.
Journal of Chinese Clinical 2003;3(1):26–7.
Zhou 2006 {published data only}
Zhou Q. Clinical analysis of acanthopanax injection for 228
patients with ischaemic stroke. Guangxi Medical Journal
2006;28(9):1396–7.
Additional references
Deyama 2001
Deyama T, Nishibe S, Nakazawa Y. Constituents and
pharmacological effects of Eucommia and Siberian Ginseng.
Acta Pharmacologica Sinica 2001;22(12):1057–70.
Duncan 2000
Duncan P, Jorgenson HS, Wade DT. Outcome measures
in acute stroke trials - a systematic review and some
recommendations to improve practice. Stroke 2000;31:
1429–38.
Fan 2003
Fan L, Jiang X, Yao G. Studies of acanthopanax injection.
Chinese Traditional Patent Medicine 2003;25(6):58–60.
Feng 1999
Feng J, Li Y, Wu J, Zhou C, Rao M. Protective effects of
acanthopanax senticosus on cerebral vascular spasm and
brain edema induced by experimental SAH in dogs. Journal
of Apoplexy and Nervous Diseases 1999;16(3):133–4.
Acanthopanax for acute ischaemic stroke (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Feng 2003
Feng G, Wang C, Wei J. Protective effects of Acanthopanax
senticosus (Rupr.et Maxim.) Harms used for the injection
on the brain ischemia in mice and rats. Journal of Shenyang
Pharmaceutical University 2003;20(1):38–40.
Fisher 2000
Fisher M, Schabitz UR. An overview of acute stroke therapy.
Archives of Internal Medicine 2000;160:3196–4006.
Han 1998
Han L, Cai D. Clinical and experimental study on
treatment of acute cerebral infarction with acanthopanax
injection. Chinese Journal of Integrated Traditional and
Western Medicine 1998;18(8):472–4.
Jiang 2004
Jiang H, Sui D, Yu X, Du S, Xu H, Wang Z, et al.Effects of
acanthopanax senticosus saponins (ASS) on hemorrheology
and platelet function in experimental cerebral ischemia rats.
Journal of Jilin University (Medicine Edition) 2004;30(3):
384–6.
Li 2006
Li K. A systematic review of acanthopanax injection for
acute ischaemic stroke. Chinese Traditional Patent Medicine
2006;28(10):1458–61.
Lu 2002
Lu Z, Xiong L, Wang Q, Zheng Y, Zhang X. Protective
effects of acanthopanax senticosus injection on focal cerebral
ischaemic injury in rats. Journal of the Fourth Military
Medical University 2002;23(8):698–700.
Sandercock 2003
Sandercock P, Gubitz G, Foley P, Counsell C. Antiplatelet
therapy for acute ischaemic stroke. Cochrane Database
of Systematic Reviews 2003, Issue 2. [DOI: 10.1002/
14651858.CD000029]
Sulter 1999
Sulter G, Steen C, De Keyser J. Use of the Barthel Index
and Modified Rankin Scale in acute stroke trials. Stroke
1999;30:1538–40.
Vickers 1998
Vickers A, Goyal N, Harland R, Rees R. Do certain
countries produce only positive results? A systematic review
of controlled trials. Controlled Clinical Trials 1998;19:
159–66.
Wang 2003
Wang Z, Lin J, Zhang Z. Studies on constituents and
pharmacological effects of acanthopanax senticosus. Journal
of Chinese Medicinal Materials 2003;26(8):603–6.
Wardlaw 2003
Wardlaw JM, del Zoppo G, Yamaguchi T, Berge E.
Thrombolysis for acute ischaemic stroke. Cochrane Database
of Systematic Reviews 2003, Issue 3. [DOI: 10.1002/
14651858.CD000213]
WHO 2003
World Health Organization. Traditional medicine.
www.who.int/mediacentre/factsheets/fs134/en/ (accessed
15 September 2007).
8
Zhang 2000
Zhang D, Tian J, Wang H, Cheng W, Xu W, Fang H.
Protective action of radix et caulis acanthopanacis senticosi
injection on diastolic function of pig coronary artery in
vitro injured by oxygen free radical. Chinese Traditional
Patent Medicine 2000;22(11):779–81.
Zhu 1999
Zhu Y, Cai W, He Y, Xu J. Observation on curative
effects of acanthopanax root injection on treating acutely
deteriorative phase of cor pulmonale. Chinese Journal of
Integrated Traditional and Western Medicine in Intensive and
Critical Care 1999;6(11):502–4.
∗
Indicates the major publication for the study

Acanthopanax for acute ischaemic stroke (Review) 9

Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
CHARACTERISTICS OF STUDIES

Characteristics of included studies [ordered by study ID]

He 1998

Methods RCT: random allocation was reported but method of randomisation and concealment
not reported
Blinding: not reported
ITT analysis: not reported
Losses to follow up: none

Participants Inclusion criteria: clinical diagnosis of acute ischaemic stroke (CT scan proven)
Exclusion criteria: not reported
Country: China
70 participants (36 treatment, 34 control)
Comparability: age, sex, MESSS score and stroke severity similar, more males than
females
Stroke severity:
Treatment group: mild - 20 participants; moderate - 10 participants; severe - 6 partici-
pants
Control group: mild - 16 participants; moderate - 11 participants; severe - 7 participants
The timing of the start of treatment after stroke onset not reported

Interventions Treatment: acanthopanax 40 ml once daily plus nimodipine capsule 20 mg three times
daily for 14 days
Control: nimodipine capsule 20 mg three times daily for 14 days
Both groups: routine drug therapy

Outcomes Number of participants with neurological improvement (MESSS score decrease > 18%)
at 14 days

Notes Follow up: 14 days

Risk of bias

Item Authors’ judgement Description

Adequate sequence generation? Unclear Random allocation reported but the

method of randomisation was not de-
scribed

Allocation concealment? Unclear Method of randomisation and conceal-

ment not reported

Blinding? Unclear Not reported

participants,personnel and outcome asses-
sors

Acanthopanax for acute ischaemic stroke (Review) 10

Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
He 1998 (Continued)

Incomplete outcome data addressed? Unclear Not reported

All outcomes

Jia 1998

Methods RCT: random allocation was reported but method of randomisation and concealment
not reported
Blinding: not reported
ITT analysis: not reported
Losses to follow up: none

Participants Inclusion criteria: acute ischaemic stroke diagnosis on CT scan

Exclusion criteria: not reported
Country: China
62 participants (31 treatment, 31 control)
Comparability: age, sex, stroke severity and location of stroke similar, more males than
females
Numbers of severity of stroke not reported
The timing of the start of treatment after stroke onset was 3 hours to 1 week

Interventions Treatment: acanthopanax 50 ml plus hydroxyethy starch 500 ml with danshen 20 ml

once daily for 28 days
Control: hydroxyethy starch 500 ml with danshen 20 ml once daily for 28 days

Outcomes Number of participants with neurological improvement (defined by the trialists’ own
definition, which is similar to MESSS) at 28 days

Notes Follow up: 28 days

Risk of bias

Item Authors’ judgement Description

Adequate sequence generation? Unclear Random allocation reported but the

method of randomisation was not de-
scribed

Allocation concealment? Unclear Method of randomisation and conceal-

ment not reported

Blinding? Unclear Not reported

participants,personnel and outcome asses-
sors

Incomplete outcome data addressed? Unclear Not reported

All outcomes

Acanthopanax for acute ischaemic stroke (Review) 11

Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Li 2007

Methods RCT: random allocation was reported but method of randomisation and concealment
not reported
Blinding: not reported
ITT analysis: not reported
Losses to follow up: none

Participants Inclusion criteria: start within 72 hours, clinical diagnosis of acute ischaemic stroke (CT
scan proven)
Exclusion criteria: intracranial haemorrhage
Country: China
93 participants (52 treatment, 41 control)
Comparability: age, sex, MESSS score similar, more males than females
Numbers of severity of stroke not reported
The timing of the start of treatment after stroke onset not reported

Interventions Treatment: acanthopanax 30 ml once daily for 10 days plus defibrase 10 u at first dosage
and afterwards 5 u once every 2 days, 3 times in all
Control: defibrase 10 u at first dosage and afterwards 5 u once every 2 days, 3 times in
all
Both groups: routine drug therapy

Outcomes Number of participants with neurological improvement (MESSS score decrease > 18%)
at 28 days

Notes Follow up: 28 days

Risk of bias

Item Authors’ judgement Description

Adequate sequence generation? Unclear Random allocation reported but the

method of randomisation was not de-
scribed

Allocation concealment? Unclear Method of randomisation and conceal-

ment not reported

Blinding? Unclear Not reported

participants,personnel and outcome asses-
sors

Incomplete outcome data addressed? Unclear Not reported

All outcomes

Acanthopanax for acute ischaemic stroke (Review) 12

Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Long 2000

Methods RCT: random allocation was reported but method of randomisation and concealment
not reported
Blinding: not reported
ITT analysis: not reported
Losses to follow up: none

Participants Inclusion criteria: start within 6 hours to 3 days, clinical diagnosis of acute ischaemic
stroke (CT scan proven)
Exclusion criteria: intracranial haemorrhage, simple inco-ordination or loss of conscious-
ness, multiple organ failure, malignant tumour, BP > 180/110mmhg
Country: China
60 participants (30 treatment, 30 control)
Comparability: age, sex, complications similar, more males than females
Numbers of severity of stroke not reported
The timing of the start of treatment after stroke onset not reported

Interventions Treatment: acanthopanax 80 ml once daily plus urokinase 0.1 million units twice daily
for 14 days
Control: basic treatment twice daily for 14 days

Outcomes Number of participants with neurological improvement (defined by the trialists’ own
definition, which is similar to MESSS) at 14 days

Notes Follow up: 14 days

Risk of bias

Item Authors’ judgement Description

Adequate sequence generation? Unclear Random allocation reported but the

method of randomisation was not de-
scribed

Allocation concealment? Unclear Method of randomisation and conceal-

ment not reported

Blinding? Unclear Not reported

participants,personnel and outcome asses-
sors

Incomplete outcome data addressed? Unclear Not reported

All outcomes

Acanthopanax for acute ischaemic stroke (Review) 13

Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Peng 2006

Methods RCT: participants were allocated according to a random number table but the method
of concealment was not reported
Blinding: not reported
ITT analysis: not reported
Losses to follow up: none

Participants Inclusion criteria: start within 6 hours to 3 days, clinical diagnosis of acute ischaemic
stroke (CT or MRI scan proven)
Exclusion criteria: serious cardiac, renal, hepatic, pulmonary, endocrine or metabolic
diseases
Country: China
100 participants (50 treatment, 50 control)
Comparability: age, sex, clinical symptom, course of disease similar, more males than
females
Numbers of severity of stroke not reported
The timing of the start of treatment after stroke onset not reported

Interventions Treatment: acanthopanax 250 ml plus basic treatment once daily for 14 days
Control: basic treatment once daily for 14 days

Outcomes Number of participants with neurological improvement (MESSS score decrease > 18%)
at 14 days

Notes Follow up: 14 days

Risk of bias

Item Authors’ judgement Description

Adequate sequence generation? Yes Participants allocated according to a ran-

dom number table

Allocation concealment? Unclear Method of concealment not reported

Blinding? Unclear Not reported

participants,personnel and outcome asses-
sors

Incomplete outcome data addressed? Unclear Not reported

All outcomes

Acanthopanax for acute ischaemic stroke (Review) 14

Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Qin 2001

Methods RCT: random allocation reported but method of randomisation and concealment not
reported
Blinding: not reported
ITT analysis: not reported
Losses to follow up: none

Participants Inclusion criteria: start within 24 hours, clinical diagnosis of acute ischaemic stroke (CT
or MRI scan proven)
Exclusion criteria: death within 48 hours from stroke onset
Country: China
86 participants (43 treatment, 43 control)
Comparability: age, sex, clinical symptom, location of stroke similar, more males than
females
Numbers of severity of stroke not reported
The timing of the start of treatment after stroke onset not reported

Interventions Treatment: acanthopanax 60 ml once daily for 14 days plus defibrase 10 u at first dosage
and afterwards 5 u once every 2 days, 4 times in all
Control: defibrase 10 u at first dosage and afterwards 5 u once every 2 days, 4 times in
all
Both groups: routine drug therapy

Outcomes Number of participants with neurological improvement (MESSS score decrease > 18%)
at 14 days

Notes Follow up: 14 days

Risk of bias

Item Authors’ judgement Description

Adequate sequence generation? Unclear Random allocation reported but the

method of randomisation was not de-
scribed

Allocation concealment? Unclear Method of randomisation and conceal-

ment not reported

Blinding? Unclear Not reported

participants,personnel and outcome asses-
sors

Incomplete outcome data addressed? Unclear Not reported

All outcomes

Acanthopanax for acute ischaemic stroke (Review) 15

Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Wang 2006

Methods RCT: random allocation reported but method of randomisation and concealment not
reported
Blinding: not reported
ITT analysis: not reported
Losses to follow up: none

Participants Inclusion criteria: clinical diagnosis of acute ischaemic stroke (CT or MRI scan proven)
Exclusion criteria: haemorrhagic stroke, cerebral tumour, etc
Country: China
60 participants (30 treatment, 30 control)
Comparability: age, sex, course of disease, location of stroke and complication similar,
more males than females
Numbers of severity of stroke not reported
The timing of the start of treatment after stroke onset not reported

Interventions Treatment: acanthopanax 80 ml plus basic treatment once daily for 15 days
Control: basic treatment once daily for 15 days

Outcomes Number of participants with neurological improvement (MESSS score decrease > 18%)
at 15 days

Notes Follow up: 15 days

Risk of bias

Item Authors’ judgement Description

Adequate sequence generation? Unclear Random allocation reported but the

method of randomisation was not de-
scribed

Allocation concealment? Unclear Method of randomisation and conceal-

ment not reported

Blinding? Unclear Not reported

participants,personnel and outcome asses-
sors

Incomplete outcome data addressed? Unclear Not reported

All outcomes

Acanthopanax for acute ischaemic stroke (Review) 16

Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Wen 2005

Methods RCT: random allocation reported but method of randomisation and concealment not
reported
Blinding: not reported
ITT analysis: not reported
Losses to follow up: none

Participants Inclusion criteria: 50 to 80 years, start within 1 week, clinical diagnosis of acute ischaemic
stroke (CT or MRI scan proven)
Exclusion criteria: moderate to severe coma, haemorrhagic disease, BP > 200/110 mmHg,
severe arrhythmia, disturbance of blood coagulation, severe pulmonary disorder, use of
thrombolysis, anticoagulation and other stroke treatment, other severe disorder
Country: China
83 participants (43 treatment, 40 control)
Comparability: age, sex similar, more males than females
Numbers of severity of stroke not reported
The timing of the start of treatment after stroke onset not reported

Interventions Treatment: acanthopanax 60 ml plus 2.5 ATA hyperbaric oxygen 80 minutes with having
a rest for 20 minutes every 40 minute once daily for 15 days
Control : 2.5 ATA hyperbaric oxygen 80 minutes with having a rest for 20 minutes every
40 minutes once daily for 15 days
Both groups: routine drug therapy

Outcomes Number of participants with neurological improvement (defined by the trialists’ own
definition which is similar to MESSS) at 15 days

Notes Follow up: 15 days

Risk of bias

Item Authors’ judgement Description

Adequate sequence generation? Unclear Random allocation reported but the

method of randomisation was not de-
scribed

Allocation concealment? Unclear Method of randomisation and conceal-

ment not reported

Blinding? Unclear Not reported

participants,personnel and outcome asses-
sors

Incomplete outcome data addressed? Unclear Not reported

All outcomes

Acanthopanax for acute ischaemic stroke (Review) 17

Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Wu 2000

Methods RCT: random allocation reported but method of randomisation and concealment not
reported
Blinding: not reported
ITT analysis: not reported
Losses to follow up: none

Participants Inclusion criteria: acute ischaemic stroke diagnosis on CT scan

Exclusion criteria: not reported
Country: China
78 participants (42 treatment, 36 control)
Comparability: age, sex, stroke severity and location of stroke similar
Stroke severity:
Treatment Group: mild - 5 participants; moderate - 33 participants; severe - 4 partici-
pants
Control Group: mild - 4 participants; moderate - 29 participants; severe - 3 participants
The timing of the start of treatment after stroke onset not reported

Interventions Treatment: acanthopanax 60 ml plus buflomedil 200 mg once daily for 20 days
Control: buflomedil 200 mg once daily for 20 days

Outcomes Number of participants with neurological improvement (defined by the trialists’ own
definition which is similar to MESSS) at 20 days

Notes Follow up: 20 days

Risk of bias

Item Authors’ judgement Description

Adequate sequence generation? Unclear Random allocation reported but the

method of randomisation was not de-
scribed

Allocation concealment? Unclear Method of randomisation and conceal-

ment not reported

Blinding? Unclear Not reported

participants,personnel and outcome asses-
sors

Incomplete outcome data addressed? Unclear Not reported

All outcomes

Acanthopanax for acute ischaemic stroke (Review) 18

Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Xiao 2007

Methods RCT: random allocation reported but method of randomisation and concealment not
reported
Blinding: not reported
ITT analysis: not reported
Losses to follow up: none

Participants Inclusion criteria: acute ischaemic stroke diagnosis on CT scan

Exclusion criteria: TIA, cerebral tumour, cerebral trauma, cerebral parasite, dys-
metabolism diseases, cerebral embolism, serious abnormal renal, hepatic or hematopoi-
etic function, psychiatric disturbance
Country: China
62 participants (37 treatment, 25 control)
Comparability: age, sex, clinical symptoms similar, more males than females
Numbers of severity of stroke not reported
The timing of the start of treatment after stroke onset not reported

Interventions Treatment: acanthopanax 250 ml plus buflomedil 150 mg once daily for 28 days
Control: buflomedil 150 mg once daily for 28 days
Both groups: routine drug therapy

Outcomes Number of participants with neurological improvement (MESSS score decrease > 18%)
at 28 days

Notes Follow up: 28 days

Risk of bias

Item Authors’ judgement Description

Adequate sequence generation? Unclear Random allocation reported but the

method of randomisation was not de-
scribed

Allocation concealment? Unclear Method of randomisation and conceal-

ment not reported

Blinding? Unclear Not reported

participants,personnel and outcome asses-
sors

Incomplete outcome data addressed? Unclear Not reported

All outcomes

Acanthopanax for acute ischaemic stroke (Review) 19

Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Xu 2003

Methods RCT: random allocation reported but method of randomisation and concealment not
reported
Blinding: not reported
ITT analysis: not mentioned
Losses to follow up: none

Participants Inclusion criteria: start within 48 hours, first-ever stroke, clinical diagnosis of acute
ischaemic stroke (CT or MRI scan proven)
Exclusion criteria: haemorrhagic infarction, haemorrhagic tendency or disturbance of
blood coagulation, serious abnormal cardiac, renal, hepatic or lung function, use of
thrombolysis, anticoagulation and haemodilution, etc
Country: China
112 participants (56 treatment, 56 control)
Comparability: age, sex, course of disease, stroke severity, location of stroke and compli-
cations similar
Stroke severity:
Treatment Group: mild - 22 participants; moderate - 30 participants; severe - 4 partici-
pants
Control Group: mild - 23 participants; moderate - 31 participants; severe - 2 participants
The timing of the start of treatment after stroke onset not reported

Interventions Treatment: acanthopanax 60 ml once daily plus low-molecular heparin 0.4 ml twice
daily for 14 days
Control: low-molecular heparin 0.4 ml twice daily for 14 days
Both groups: routine drug therapy

Outcomes Number of participants with neurological improvement (MESSS score decrease > 18%)
at 14 days

Notes Follow up: 14 days

Risk of bias

Item Authors’ judgement Description

Adequate sequence generation? Unclear Random allocation reported but the

method of randomisation was not de-
scribed

Allocation concealment? Unclear Method of randomisation and conceal-

ment not reported

Blinding? Unclear Not reported

participants,personnel and outcome asses-
sors

Incomplete outcome data addressed? Unclear Not reported

All outcomes

Acanthopanax for acute ischaemic stroke (Review) 20

Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Ye 2003

Methods RCT: random allocation reported but method of randomisation and concealment not
reported
Blinding: not reported
ITT analysis: not reported
Losses to follow up: none

Participants Inclusion criteria: start within 2 weeks, clinical diagnosis of acute ischaemic stroke (CT
scan proven)
Exclusion criteria: not reported
Country: China
40 participants (20 treatment, 20 control)
Comparability: unclear
Numbers of severity of stroke not reported
The timing of the start of treatment after stroke onset not reported

Interventions Treatment: acanthopanax 60 to 80 ml plus basic treatment once daily for 30 days
Control: basic treatment once daily for 30 days

Outcomes Number of participants with neurological improvement (defined by the trialists’ own
definition which is similar to MESSS) at 30 days

Notes Follow up: 30 days

Risk of bias

Item Authors’ judgement Description

Adequate sequence generation? Unclear Random allocation reported but the

method of randomisation was not de-
scribed

Allocation concealment? Unclear Method of randomisation and conceal-

ment not reported

Blinding? Unclear Not reported

participants,personnel and outcome asses-
sors

Incomplete outcome data addressed? Unclear Not reported

All outcomes

Acanthopanax for acute ischaemic stroke (Review) 21

Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Yu 2002

Methods RCT: random allocation reported but method of randomisation and concealment not
reported
Blinding: not reported
ITT analysis: not reported
Losses to follow up: none

Participants Inclusion criteria: clinical diagnosis of acute ischaemic stroke (CT scan proven)
Exclusion criteria: not mentioned
Country: China
56 participants (28 treatment, 28 control)
Comparability: age, sex, clinical symptoms similar, more males than females
Numbers of severity of stroke not reported
The timing of the start of treatment after stroke onset is 1 to 3 days

Interventions Treatment: acanthopanax 40 to 60 ml plus basic treatment once daily for 14 days
Control: basic treatment once daily for 14 days

Outcomes Number of participants with neurological improvement (MESSS score decrease > 18%)
at 14 days

Notes Follow up: 14 days

Risk of bias

Item Authors’ judgement Description

Adequate sequence generation? Unclear Random allocation reported but the

method of randomisation was not de-
scribed

Allocation concealment? Unclear Method of randomisation and conceal-

ment not reported

Blinding? Unclear Not reported

participants,personnel and outcome asses-
sors

Incomplete outcome data addressed? Unclear Not reported

All outcomes

ATA: atmosphere absolute

BP: blood pressure
CT: computerised tomography
ITT: intention to treat
MESSS: Modified Edinburgh Scandinavian Stroke Scale
MRI: magnetic resonance imaging
RCT: randomised controlled trial
TIA: transient ischaemic attack

Acanthopanax for acute ischaemic stroke (Review) 22

Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Characteristics of excluded studies [ordered by study ID]

Study Reason for exclusion

Cai 2005 Stage of stroke not reported

Dong 2001 Not a RCT

Du 2003 Three studies including the same participants with different blood examination indexes were published in different
journals; MESSS was assessed before and after treatment period but the proportion of participants with improvement
of neurological deficit was not available. We cannot obtain usable data for analysis

Du 2004a Three studies including the same participants with different blood examination indexes were published in different
journals; MESSS was assessed before and after treatment period but the proportion of participants with improvement
of neurological deficit was not available. We cannot obtain usable data for analysis

Du 2004b Three studies including the same participants with different blood examination indexes were published in different
journals; MESSS was assessed before and after treatment period but the proportion of participants with improvement
of neurological deficit was not available. Wecan not obtain usable data for analysis

Fan 2000 Not a RCT

Hu 2000 Quasi-RCT, because participants allocated alternately according to date of admission

Jiang 2003 Quasi-RCT, because participants allocated alternately according to sequence of admission

Kuang 2001 The basic treatment in both groups was unclear: mailuoning and dextran were given to some participants but not
others

Wang 2005 Quasi-RCT, because participants allocated alternately according to sequence of admission

Wu 2002 Quasi-RCT, because participants allocated alternately according to date of admission

Zhang 2005 Not a RCT

Zhou 2003 Not a RCT

Zhou 2006 Not a RCT

MESSS: Modified Edinburgh Scandinavian Stroke Scale

RCT: randomised controlled trial

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Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
DATA AND ANALYSES

Comparison 1. Acanthopanax versus control

No. of No. of
Outcome or subgroup title studies participants Statistical method Effect size

1 Improvement of neurological 13 962 Risk Ratio (M-H, Fixed, 95% CI) 1.22 [1.15, 1.29]
deficit at the end of treatment
1.1 MESSS 8 639 Risk Ratio (M-H, Fixed, 95% CI) 1.17 [1.10, 1.25]
1.2 As defined by the trialists 5 323 Risk Ratio (M-H, Fixed, 95% CI) 1.31 [1.17, 1.47]

Analysis 1.1. Comparison 1 Acanthopanax versus control, Outcome 1 Improvement of neurological deficit
at the end of treatment.
Review: Acanthopanax for acute ischaemic stroke

Comparison: 1 Acanthopanax versus control

Outcome: 1 Improvement of neurological deficit at the end of treatment

Study or subgroup Acanthopanax Control Risk Ratio Weight Risk Ratio

n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
1 MESSS
He 1998 33/36 25/34 7.1 % 1.25 [ 1.00, 1.56 ]

Li 2007 48/52 34/41 10.5 % 1.11 [ 0.95, 1.31 ]

Peng 2006 43/50 32/50 8.8 % 1.34 [ 1.06, 1.70 ]

Qin 2001 41/43 39/43 10.7 % 1.05 [ 0.94, 1.18 ]

Wang 2006 28/30 24/30 6.6 % 1.17 [ 0.95, 1.43 ]

Xiao 2007 36/37 22/25 7.2 % 1.11 [ 0.95, 1.29 ]

Xu 2003 52/56 41/56 11.3 % 1.27 [ 1.07, 1.51 ]

Yu 2002 27/28 25/28 6.9 % 1.08 [ 0.93, 1.25 ]

Subtotal (95% CI) 332 307 69.2 % 1.17 [ 1.10, 1.25 ]

Total events: 308 (Acanthopanax), 242 (Control)
Heterogeneity: Chi2 = 7.93, df = 7 (P = 0.34); I2 =12%
Test for overall effect: Z = 4.86 (P < 0.00001)
2 As defined by the trialists
Jia 1998 30/31 22/31 6.1 % 1.36 [ 1.08, 1.72 ]

0.5 0.7 1 1.5 2

Favours control Favours Acanthopanax
(Continued . . . )

Acanthopanax for acute ischaemic stroke (Review) 24

Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 (. . . Continued)
Study or subgroup Acanthopanax Control Risk Ratio Weight Risk Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Long 2000 25/30 23/30 6.3 % 1.09 [ 0.84, 1.40 ]

Wen 2005 37/43 20/40 5.7 % 1.72 [ 1.23, 2.40 ]

Wu 2000 40/42 27/36 8.0 % 1.27 [ 1.04, 1.55 ]

Ye 2003 19/20 17/20 4.7 % 1.12 [ 0.91, 1.38 ]

Subtotal (95% CI) 166 157 30.8 % 1.31 [ 1.17, 1.47 ]

Total events: 151 (Acanthopanax), 109 (Control)
Heterogeneity: Chi2 = 7.09, df = 4 (P = 0.13); I2 =44%
Test for overall effect: Z = 4.66 (P < 0.00001)
Total (95% CI) 498 464 100.0 % 1.22 [ 1.15, 1.29 ]
Total events: 459 (Acanthopanax), 351 (Control)
Heterogeneity: Chi2 = 18.90, df = 12 (P = 0.09); I2 =36%
Test for overall effect: Z = 6.72 (P < 0.00001)

0.5 0.7 1 1.5 2

Favours control Favours Acanthopanax

APPENDICES

Appendix 1. MEDLINE search strategy

We used the following search strategy, using a combination of controlled vocabulary and text word terms, for MEDLINE (Ovid) and
modified it to suit the other databases.
1. cerebrovascular disorders/ or basal ganglia cerebrovascular disease/ or exp brain ischemia/ or carotid artery diseases/ or carotid artery
thrombosis/ or cerebrovascular accident/ or exp brain infarction/ or exp hypoxia-ischemia, brain/ or intracranial arterial diseases/ or
cerebral arterial diseases/ or exp “intracranial embolism and thrombosis”/
2. (stroke$ or apoplex$ or cerebral vasc$ or cerebrovasc$ or cva or transient isch?emic attack$ or tia$).tw.
3. (brain or cerebr$ or cerebell$ or vertebrobasil$ or hemispher$ or intracran$ or intracerebral or infratentorial or supratentorial or
middle cerebr$ or mca$ or anterior circulation).tw.
4. (isch?emi$ or infarct$ or thrombo$ or emboli$ or occlus$ or hypoxi$).tw.
5. 3 and 4
6. 1 or 2 or 5
7. acanthopanax/ or eleutherococcus/
8. Plants, Medicinal/ or exp Medicine, Oriental Traditional/ or Drugs, Chinese Herbal/
9. (acanthopanax or ciwujia or ci wu jia or ci-wu-jia or eleutherococc$ or siberian ginseng or ereuterokoko).tw.
10. (acanthopanax or ciwujia or ci wu jia or ci-wu-jia or eleutherococc$ or siberian ginseng or ereuterokoko).nm.
11. 7 or 8 or 9 or 10
12. 6 and 11
13. limit 12 to humans

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Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
HISTORY
Protocol first published: Issue 2, 2008
Review first published: Issue 3, 2009

Date Event Description

17 June 2008 Amended Converted to new review format.

CONTRIBUTIONS OF AUTHORS
Draft the protocol: Weizheng Li, Ming Liu, Shejun Feng, Bo Wu
Develop the search strategy: Weizheng Li, Bo Wu, Shihong Zhang
Search for trials: Weizheng Li, Shejun Feng, Bo Wu
Obtain copies of trials: Weizheng Li, Bo Wu, Shejun Feng, Weimin Yang
Select trials to include: Weizheng Li, Shejun Feng, Ming Liu
Extract data from trials: Weizheng Li, Shejun Feng
Enter data into RevMan: Weizheng Li, Shejun Feng
Carry out the analysis: Weizheng Li, Bo Wu, Guanjian Liu
Interpret the analysis: Weizheng Li, Ming Liu
Draft the final review: Weizheng Li, Ming Liu, Shejun Feng, Bo Wu
Update the review : Weizheng Li, Ming Liu, Shejun Feng, Bo Wu

DECLARATIONS OF INTEREST
None known.

INDEX TERMS
Medical Subject Headings (MeSH)
∗ Eleutherococcus; Brain Ischemia [complications; ∗ drug therapy]; Drugs, Chinese Herbal [∗ therapeutic use]; Phytotherapy [∗ methods];

Randomized Controlled Trials as Topic; Stroke [∗ drug therapy; etiology]

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Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
MeSH check words
Humans

Acanthopanax for acute ischaemic stroke (Review) 27

Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.