1. health and fitness
2. disease
3. heart disease

Clinical Sciences
Acupuncture Efficacy on Ischemic Stroke Recovery
Multicenter Randomized Controlled Trial in China
Shihong Zhang, MD, PhD*; Bo Wu, MD, PhD*; Ming Liu, MD, PhD; Ning Li, MD, PhD;
Xianrong Zeng, MD, PhD; Hua Liu, MD, PhD; Qingcheng Yang, MD; Zhao Han, MD;
Ping Rao, MD; Dong Wang, MD; on behalf of all Investigators
Background and Purpose—Acupuncture is a frequently used complementary treatment for ischemic stroke in China but the
evidence available from previous randomized trials is inconclusive. The objective of this study was to assess the efficacy
and safety of acupuncture in a more robustly designed larger scale trial.
Methods—This is a multicenter, single-blinded, randomized controlled trial. Eight hundred sixty-two hospitalized patients
with limb paralysis between 3 to 10 days after ischemic stroke onset were allocated acupuncture plus standard care or
standard care alone. The acupuncture was applied 5 times per week for 3 to 4 weeks. The primary outcomes were defined
as follows: (1) death/disability according to Barthel index and (2) death/institutional care at 6 months.
Results—There was a tendency of fewer patients being dead or dependent in acupuncture group (80/385, 20.7%) than in
control group (102/396, 25.8%) at 6 months (odds ratio, 0.75; 95% confidence interval, 0.54–1.05). The benefit was noted
in subgroup receiving ≥10 sessions of acupuncture (odds ratio, 0.68; 95% confidence interval, 0.47–0.98). There was
no statistical difference in death or institutional care between the 2 groups (odds ratio, 1.06; 95% confidence interval,
0.63–1.79). Severe adverse events occurred in 7.6% and 8.3% of patients in the 2 groups, respectively.
Conclusions—Acupuncture seemed to be safe in the subacute phase of ischemic stroke. If the potential benefits observed are
confirmed in future larger study, the health gain from wider use of the treatment could be substantial.
Clinical Trial Registration—URL: http://www.chictr.org/en/. Unique identifier: ChiCTR-TRC-11001353. (Stroke. 2015;46:00-00. DOI: 10.1161/STROKEAHA.114.007659.)
Key Words: acupuncture ◼ clinical trial ◼ stroke
W
orldwide, stroke is the second common cause of death
and first leading cause of adult disability.1 In China,
there are 1.5 to 2 million new strokes per year and stroke has
become the first leading cause of death and disabilty.2,3 The
proportion of patients being dependent in daily life is still high
at discharge even in those with intensive treatment including rehabilitation.4 In Western medicine, treatment added in
standard rehabilitation in the early postacute phase of stroke
that might promote the process of recovery such as selective
serotonin reuptake inhibitors and constraint-induced movement therapy shows great promise.5,6 Acupuncture which has
been used for treating stroke for >1000 years might act in a
similar way. Experimental studies have showed its potential
beneficial effects in post stroke rehabilitation.7–10 However,
randomized controlled trials have yet to show convincing evidence of benefit in acute and subacute ischemic stroke.11–13 In
the earlier trials conducted outside China, 2 studies showed
that acupuncture can improve motor function and independence in activities of daily living (ADL),14,15 whereas 2 trials
using sham treatment as control did not find evidence of benefit.16,17 Although, by contrast, many Chinese trials reported
positive results, the conclusions were not regarded as robust,
as a result of small sample size and methodological weaknesses as follows: the use of outcome measures that were not
internationally recognized; unclear methods of randomization
and allocation concealment; the lack of long-term follow-up;
and publication bias.12,13,18 Therefore, we designed this randomized controlled trials with a larger sample, and scales to
Received October 4, 2014; final revision received March 18, 2015; accepted March 18, 2015.
From the Department of Neurology (S.Z., B.W., M.L.) and Department of Acupuncture and Moxibustion (N.L.), West China Hospital, State Key
Laboratory of Biotherapy and Cancer Center, Sichuan University, Chengdu, Sichuan Province, China; Department of Neurology (X.Z.), the People’s
Hospital of Sichuan province, Chengdu, Sichuan Province, China; Department of Neurology (H.L.), the Second Clinical Medical College of North Sichuan
Medical College and Nanchong Central Hospital, Nanchong, China; Department of Neurology (Q.Y.), the People’s Hospital of Anyang City, Anyang,
Henan Province, China; Department of Neurology (Z.H.), the first Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang Province, China;
Department of Neurology (P.R.), the First People’s Hospital of Chengdu City, Chengdu, Sichuan Province, China; and the Department of Neurology
(D.W.), the Third Affiliated Hospital of Neimenggu Medical College, Baotou, Neimenggu Autonomous Region, China.
*Drs Zhang and Wu contributed equally.
The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.
114.007659/-/DC1.
Correspondence to Ming Liu, MD, PhD, Stroke Clinical Research Unit, Department of Neurology, West China Hospital, State Key Laboratory of
Biotherapy and Cancer Center, Sichuan University, 37 Guo Xue Xiang, Chengdu 610041, Sichuan Province, P R China. E-mail wyplmh@hotmail.com
© 2015 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org
DOI: 10.1161/STROKEAHA.114.007659
Downloaded from http://stroke.ahajournals.org/ at1CONS CALIFORNIA DIG LIB on April 16, 2015
2 Stroke May 2015
assess efficacy and safety of acupuncture. The hypothesis was
acupuncture, in the immediate postacute phase of ischemic
stroke, can improve patients’ independence in ADL over a
longer follow-up.
Methods
Study Design and Participants
This study was designed as a multicenter, single-blinded, randomized controlled trial. The study was divided into 2 phases: pilot
study from April 2001 to February 2002 and main study from
February 2002 to February 2004. The study was registered in
Chinese Clinical Trial Register (ChiCTR-TRC-11001353) with
protocol approved by the ethics committee of West China Hospital
of Sichuan University.
Inclusion Criteria
Patients aged from 18 to 85 years and both sexes were eligible if they
had an acute ischemic stroke and could be enrolled between 3 to 10
days after stroke onset. The ischemic stroke was diagnosed according
to the World Health Organization criteria for stroke and all patients
had brain computed tomographic or magnetic resonance imaging
scan to exclude intracerebral hemorrhage.19 Only patients with limbs
paralysis were included. The extent of paralysis had to be such that
patients should be unable to walk or eat or dress without assistance.
Exclusion Criteria
The criteria included the following: (1) dependency in ADL before
present stroke, (2) inability to complete scheduled treatment course,
(3) infection in acupuncture sites, (4) severe aphasia or unconsciousness making it difficult to comprehend the study or cooperate in evaluation, and (5) other severe complications or comorbidities such as
heart/renal function failure.
Sample Size
The sample size calculation was based on assumption of a ≥10% reduction in the absolute risk of death or dependency in the acupuncture group compared with controls (30%) at 6-month follow-up.
Considering possible loss of follow-up (10% to 20%), ≥800 patients
(400 patients in each group) were required to test the hypothesis
(α=0.05; β=0.80).
Randomization and Allocation Concealment
The list of treatment allocations were produced centrally by computer-generated random numbers and the randomization sequence was
stratified by participating centres. The article revealing the treatment
allocation was placed in sequentially numbered, sealed opaque envelopes. After informed consent was obtained, the envelopes were
opened sequentially and acupuncture therapists were notified if participants were allocated into acupuncture group.
Interventions
Patients in both groups received routine ischemic stroke treatment,
such as antithrombotic medications and prevention of complications. Rehabilitation was also performed in centres where it was
available. Background medical care could differ from center to
center but the protocol required all trial patients in a given center to receive the same background care irrespective of treatment
allocation.
Patients in the treatment group received additional traditional
Chinese acupuncture which was started 3 to 10 days after stroke
onset, 5 times per week for 3 to 4 weeks (in the pilot study) or 3
weeks (in the main study). Before the trial started, all acupuncturists
in participating centres received training of standardized acupuncture
procedure. The acupoints with corresponding needling methods used
in the present study were selected on the basis of “Xing Nao Kai
Qiao” acupuncture methods which was originally developed by the
acupuncture research group in the Medical College of Tianjing.20
The main acupoints include Renzhong-DU26, Neiguan-PC6 (both
sides), and Sanyinjiao-SP6 (paretic side). Auxiliary acupoints include Baihui-DU20, 4 acupoints on the paretic side (Zusanli-ST36,
Fenglong-ST40, Taichong-LK3, and Chize-LL5), and 2 acupoints on
the both sides (Fengchi-GB20, Qihai-RN6). The Huato sterile acupuncture needles (1.5–4 cm in length and 0.38–0.42 mm in diameter)
were used in the present study. Patients were in the supine position
when they were treated. The needling methods for each acupoint have
been published in the article of pilot study in the online-only Data
Supplement.21
Figure 1. Trial profile. BI indicates Barthel index.
Downloaded from http://stroke.ahajournals.org/ at CONS CALIFORNIA DIG LIB on April 16, 2015
Zhang et al Acupuncture in Acute Ischemic Stroke 3
Table 1. Baseline Characteristics of Participants
Acupuncture
(N=427)
Control
(N=435)
Age, y (mean±SD)
64.1±11.1
64.6±9.9
Sex, men
242 (56.7)
239 (54.9)
355 (83.1)
376 (86.4)
72 (16.9)
59 (13.6)
Primary outcomes in this trial were defined as the following: (1)
death/disability at 6 months: disability was defined as BI of ≤60
points; (2) death/long-term institutional care at 6 months (in the hospital, nursing home, or rehabilitation house). As sample size/power
calculation may vary when it is based on different primary outcomes,
sample size calculation based on outcome “death/disability at 6
months” was preset in this study. Secondary outcomes include the
following: (1) case fatality; (2) changes of neurological deficit score
at the end of scheduled treatment periods or at discharge. Severe
adverse events occurred in both groups and adverse events directly
related to acupuncture were analyzed to assess acupuncture safety.
Statistics
Characteristics
Hospital
West medicine hospital
Chinese medicine hospital
Past medical history
Stroke
71 (16.6)
78 (17.9)
221 (51.8)
244 (56.1)
Diabetes mellitus
60 (14.1)
77 (17.7)
Hyperlipidemia
36 (8.4)
46 (10.6)
Myocardial infarction
11 (2.6)
8 (1.8)
Hypertension
MRI/computed tomographic scan*
Normal
94 (22.0)
92 (21.1)
328 (76.8)
341 (78.4)
Left hemisphere
208 (48.7)
213 (49.0)
Right hemisphere
195 (45.7)
183 (42.1)
Brain stem
6 (1.4)
6 (1.4)
Cerebella
0 (0)
1 (0.2)
Multiple
15 (3.5)
24 (5.5)
Upper limb
410 (96.0)
424 (97.5)
Lower limb
414 (97.0)
428 (98.4)
Dysphasia
101 (23.7)
105 (24.1)
Dysphagia/dysarthria‡
134 (31.5)
167 (38.7)
Facial paralysis
330 (77.3)
347 (79.8)
Infarction
Lesion sites†
Neurological deficits
Limb paralysis
Ataxia
Scandinavian Stroke Scale score
(mean±SD)
23 (5.4)
27 (6.2)
32.5±11.2
33.7±15.1
*Computed tomographic scan of 1 patient showed cerebral hemorrhage
in acupuncture group. Computed tomographic scan and magnetic resonance
imaging (MRI) were not performed in 6 patients.
†Lesion site was uncertain in 11 patients.
‡Significant difference between the 2 groups (P=0.037).
Evaluations
Demographic and clinical characteristics were recorded at the time
of enrollment. During treatment period, adverse events which may
be related to acupuncture were monitored and reported to the principal investigator who would decide whether acupuncture should be
stopped. All patients who did not adhere to the allocated treatment
were followed up in full and their data were included into analysis
according to intention-to-treat principle.
The severity of neurological deficits at baseline and at the end
of scheduled treatment periods or at discharge was assessed with
Scandinavian Stroke Scale. This scale includes 10 items with total
of score ranging from 0 to 60 points (higher points indicate better
neurological function). At the end of 3 and 6 months after randomization, patients were followed up by telephone interview. ADL were
evaluated by using Barthel Index (BI) which involves 10 personal
activities with a maximum of 100 points (higher BI score indicates
better function in ADL). The evaluation of both neurological deficits and ADL were performed by investigators who were unaware of
treatment allocation.
Statistical analyses were performed by using SPSS for Windows statistic software (version 13.0). χ2 test for categorical variables, t test
for continuous variables with normal distribution, and nonparametric
test for skewed distribution were used to detect difference in baseline
characteristics between the 2 groups. For the outcome analysis, odds
ratio [OR] with corresponding 95% confidence interval [CI] were calculated for dichotomous data including death, death or disability, and
death or long-term institutional care, whereas t test was used to assess difference in changes of neurological deficits score between the
2 groups. The level of significance was set at 5% in the comparison,
and all statistical testing was 2-sided. Subgroup analysis was preset to
compare patients receiving ≥10 sessions of acupuncture with control
group.
Results
Total of 862 patients from 40 hospitals were enrolled in this
study; of them 427 were allocated acupuncture and 435 control (Figure 1). There was no significant difference in baseline
characteristics between the 2 groups except more patients with
dysphagia and dysarthria in control group than in acupuncture
group (Table 1). Two hundred sixty-seven (62.5%) patients in
acupuncture group completed all scheduled sessions of acupuncture (≥15 sessions), whereas 54 (12.6%) received 10 to
14 sessions, 59 (13.8%) received 5 to 9 sessions, 24 (5.6%)
received 1 to 4 sessions, and 23 (5.4%) did not receive any
acupuncture treatment after randomization. The main cause of
discontinuing acupuncture was early discharge from hospital
(112 patients, 82.4%). The concomitant therapies were comparable between the 2 groups (Table I in the online-only Data
Supplement).
At 6 months, 40 (9.4%) patients in acupuncture group and
39 (9.0%) patients in control group were lost to follow-up.
Fewer patients had died or were dependent in ADL in the
acupuncture group (113/410, 27.6%) than in control group
(137/405, 33%) at 3 months, the tendency continued at 6
months (80/385 [20.7%] versus 102/396 [25.8%]), but the difference was not statistically significant (OR, 0.75; 95% CI,
0.54–1.05; Table 2). There was also no significant difference
in death or institutional care between the 2 groups at 6 months
(8.0% versus 7.6%; OR, 1.06; 95% CI, 0.63–1.79). The results
above did not change significantly when last observation carried forward analysis was conducted.
Post hoc ordinal analysis was performed to assess if there
was favorable shift in distribution of scores on BI with acupuncture treatment, and a nonsignificant trend was tested
(pooled OR for shift to higher BI, 1.15; 95% CI, 0.88–1.50;
P=0.296; Figure 2). Preplanned subgroup analysis showed
that only when patients who received ≥10 sessions of acupuncture were included into analysis, a significant difference
Downloaded from http://stroke.ahajournals.org/ at CONS CALIFORNIA DIG LIB on April 16, 2015
4 Stroke May 2015
Table 2. Primary and Secondary Outcomes at 3 and 6 Months
Acupuncture Control
Odds Ratio
(N=387)
(N=396) (95% Confidence Interval)
Outcomes
Death or dependency
At 3 months*
113 (27.6) 137 (33.0)
0.77 (0.57–1.04)
At 6 months
80 (20.7) 102 (25.8)
0.75 (0.54–1.05)
At 3 months
38 (8.5)
41 (9.9)
0.93 (0.59–1.48)
At 6 months
31 (8.0)
30 (7.6)
1.06 (0.63–1.79)
At 3 months
16 (3.9)
16 (3.9)
1.01 (0.50–2.05)
At 6 months
24 (6.2)
18 (4.5)
1.39 (0.74–2.60)
Death or institutional care†
Death
*Data of 410 patients in acupuncture group and 405 patients in control group
were available at 3 months.
†Institutional care indicates that patients are cared in hospital, nursing home,
or rehabilitation unit.
was detected in death or dependency at 6 months (57/298
[19.1%] versus 102/396 [25.8%]; OR, 0.68; 95% CI,
0.47–0.98; number needed to treat 15) but not for other outcomes (Table II in the online-only Data Supplement).
Death occurred in 6.2% and 4.5% of patients in the 2 groups
at 6 months, respectively (OR, 1.39%; 95% CI, 0.74–2.60).
At the end of the scheduled treatment period, there was significantly greater change of Scandinavian Stroke Scale score
from baseline in acupuncture group (9.70±7.85) than in control group (7.57±12.58; P=0.03), which indicated that patients
in acupuncture group had greater reduction in their neurological deficit.
Severe adverse events occurred in 7.6% of patients in acupuncture group and 8.3% in control group. The most common
adverse event directly related to acupuncture is pain, moderate
or severe pain occurred in ≈9.4% patients; 1.9% of patients
discontinued acupuncture because of severe pain (Table 3).
Discussion
In this study, we assessed efficacies and safety of acupuncture
used in subacute stage of stroke; acupuncture seemed to be a
safe treatment but did not show definitive benefits of reducing
death or dependency in ADL, although a trend of better outcomes was observed in acupuncture group at 3 and 6 months.
Also, acupuncture did not prove to be efficacious in reducing
death or long-term institutional care. However, it was noted
that there was more improvement of neurological deficits in
whole acupuncture group and significant reduction of death or
dependency in subgroup receiving ≥10 sessions of acupuncture (OR, 0.68; 95% CI, 0.47–0.98).
The effect of acupuncture on death or disability observed
in this study is consistent with 3 recently published studies with long-term follow-up and 2 systematic reviews of
acupuncture in post stroke rehabilitation.13,22–25 The recent
systematic review included 56 randomized trials published
before 2009; of the evaluated, 46 used acupuncture within
1-month post stroke and only 10 took functional outcomes;
pooled OR of 38 trials was in favor of acupuncture (OR, 4.33;
95% CI, 3.09–6.08).25 Of the 56 included trials, 32 trials were
published after 2004, most of them (27 trials) were conducted
in China. None of the trials conducted outside China reported
positive results on primary outcome, whereas all Chinese trials except 1 showed positive results in favor of acupuncture.
In the Cochrane systematic review focusing on efficacy of
acupuncture in acute and subacute phases of stroke, metaanalysis of 4 trials with a total of 373 patients showed that
there was a borderline significant trend toward fewer patients
being dead or dependent (OR, 0.66; 95% CI, 0.43–0.99) in
acupuncture group than in control group.13 The meta-analysis showed more aspiring result when data of this study was
merged (OR, 0.72; 95% CI, 0.55–0.93; Figure 3). It is suggested that acupuncture might be efficacious in reducing disability but whether the effect is any moderate or less, sample
size of this trial is still under power to detect it. In fact, except
recombinant tissue-type plasminogen activator thrombolysis
within 3 hours after stroke onset, there are few interventions
in acute/subacute stage of stroke which showed ≥10% of
absolute risk reduction of death or dependency. To clarify this
issue, a larger randomized controlled trial with sample size
of >1340, according to the result of updated meta-analysis,
is needed. If the potential benefits above are confirmed, the
health gain from wider use of the acupuncture after stroke
could be substantial.26
This study has strengths. First, it is the largest randomized controlled trial of acupuncture for stroke at the moment.
Table 3. Adverse Events During Scheduled Acupuncture
Treatment Periods
Adverse Events
Acupuncture
(N=427)
Control
(N=435)
P
Value
Adverse event directly related to acupuncture
Faint
2 (0.5)
…
Dizziness
1 (0.2)
…
38 (9.4)
…
Pain (moderate or severe)
Severe adverse event
Recurrent stroke
Figure 2. Distribution of Barthel index (BI) scores and death at
6 months. BI ranges from 0 (bedridden, incontinent, and requiring constant nursing care and attention) to 100 (no symptoms or
disability). The ordinal analysis shows there was nonsignificant
increase in the likelihood of better functional outcome in acupuncture group (pooled odds ratio for shift to higher BI, 1.15;
95% confidence interval, 0.88–1.50; P=0.296).
Pneumonia and urinary tract
infection
Others*
7 (1.6)
7 (1.6)
0.97
21 (4.9)
28 (6.4)
0.34
5 (1.1)
4 (0.9)
0.72
*Other severe adverse events include alimentary tract hemorrhage (2 cases),
myocardial infarction (1 case), heart failure (1 case), head traumatic (1 case),
coma caused by high blood sugar (1 case), drug allergy (1 case), and newly
diagnosed cancers (2 cases).
Downloaded from http://stroke.ahajournals.org/ at CONS CALIFORNIA DIG LIB on April 16, 2015
Zhang et al Acupuncture in Acute Ischemic Stroke 5
Figure 3. Meta-analysis of randomized trials of acupuncture for acute/subacute stroke. #Trials were included in previous Cochrane systematic review of acupuncture for acute stroke.13 There were 29% reduction of disability or death in acupuncture group compared with
control group; the difference is significant (P=0.01). CI indicates confidence interval; and OR, odds ratio.
Second, when compared with most published Chinese acupuncture trials, this study was a real randomized trial with
adequate allocation concealment, long-term follow-up and
blinding assessment. Third, we used disability in ADL or
death as primary outcome which have been preferred in
trial of acute stroke but just adopted in a few previous trials of acupuncture for stroke. We also evaluated the efficacy
of acupuncture on death or long-term institutional care. The
use of coprimary outcomes may increase the chance of positive results in favor of the evaluated treatment. Therefore,
adjustment of P value for significance (eg, P<0.025 rather
than 0.05) should be considered. In this trial, the adjustment
of P value for significance has no real impact on the trial’s
conclusion because the P values calculated for the 2 primary
outcomes were >0.05. Finally, “Xing Nao Kai Qiao” needling
method used in this trial is one of the most commonly used
acupuncture program in China. Before this trial began, an
uncontrolled observational study of 2336 patients with stroke
suggested that it was potentially efficacious in improving
neurological deficits.27 Thus, we actually assessed efficacy
of acupuncture program which is widely accepted and most
likely proved to be efficacious.
There were 3 limitations in this study. The first limitation
is poor compliance of patients with allocated treatment, only
62.5% of patients in acupuncture group received all scheduled sessions of acupuncture, and 6% of patients in control
group withdrew and required acupuncture treatment after
randomization. The reason for this may be related to the
Chinese culture background: most Chinese patients think that
acupuncture is useful in improving neurological deficits, so
they would request for the therapy if they did not have satisfactory recovery from routine treatment. The second limitation is a little high proportion of loss of follow-up (9.4%
in acupuncture group and 9.0% control group). The 2 limitations above made the results more uncertain although sensitivity analysis excluding patient who crossed over to the other
group, and analysis by last observation carried forward did
not show significant change in the results on primary outcomes. Considering the result of subgroup analysis and main
cause of discontinuing acupuncture (early discharge from hospital), 2 weeks for acupuncture treatment period may be an
appropriate choice in future trials, especially in China. The
third limitation is that reasons for noninclusion of screened
patients were recorded only in a proportion of participating
centers, which made it difficult to assess generalizability of
the trial’s results. However, data from center with the largest
number of recruited patients (West China Hospital of Sichuan
University) indicated that ≈45% of screened patients were
excluded for ineligibility and 40% were not included because
of unavailable informed consent.
Although sham acupuncture used is the main controversy
in design of acupuncture trial, it seems to be reasonable to use
sham acupuncture as control to evaluate real or specific effect
of acupuncture. However, sham acupunctures which have
been used in some previous studies are not feasible in China
because patients are well acquainted with acupuncture and
recognize the special sensation of “Teh Chi.” Furthermore,
sham acupuncture may not be truly inert and may have underlying physiological effects, and hence may not be a proper
control group.28,29 To enable us to design a large pragmatic
trial, we decided not to use sham acupuncture as control in this
study. In contrast to previous Chinese trial in stroke, we used
binary outcome as primary outcome (dependency or independency according to BI score) because the systematic review
suggested that placebos had no significant effects on objective
or binary outcomes in clinical trials.30
In conclusion, this study assessed efficacy of acupuncture
used as adjunct to standard care in the early stage of stroke, the
result does not support its use in the routine clinical practice
from Western medicine perspective. However, a trend toward
fewer patients with dependency in acupuncture group was
noted, especially in those receiving >10 sessions of acupuncture. Trials with larger scale are needed to confirm the potential
benefit of acupuncture for post stroke rehabilitation in future.
Downloaded from http://stroke.ahajournals.org/ at CONS CALIFORNIA DIG LIB on April 16, 2015
6 Stroke May 2015
Acknowledgments
We would like to thank all doctors and patients who participated in this
study for their cooperation. We also would like to express our gratitude
to Professor Peter Sandercock of Western General Hospital, Edinburgh,
United Kingdom, and Professor KS Wong of Prince of Wales Hospital,
Hongkong for useful comments on the article of this study.
Sources of Funding
This study was funded by the State Administration of Traditional
Chinese Medicine of the People’s Republic China.
Disclosures
None.
References
1.Strong K, Mathers C, Bonita R. Preventing stroke: saving lives
around the world. Lancet Neurol. 2007;6:182–187. doi: 10.1016/
S1474-4422(07)70031-5.
2. Liu M, Wu B, Wang WZ, Lee LM, Zhang SH, Kong LZ. Stroke in China:
epidemiology, prevention, and management strategies. Lancet Neurol.
2007;6:456–464. doi: 10.1016/S1474-4422(07)70004-2.
3. Chen Z. The mortality and death cause of national sample areas. In: Chen
Z, ed. The Third National Survey on the Cause of Death. 1st ed. Beijing:
Peking Union Medical University Press; 2008:14–15.
4. Sze KH, Wong E, Or KH, Lum CM, Woo J. Factors predicting stroke
disability at discharge: a study of 793 Chinese. Arch Phys Med Rehabil.
2000;81:876–880.
5. Mead GE, Hsieh CF, Lee R, Kutlubaev MA, Claxton A, Hankey GJ, et
al. Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery.
Cochrane Database Syst Rev. 2012;11:CD009286.
6. Sirtori V, Corbetta D, Moja L, Gatti R. Constraint-induced movement
therapy for upper extremities in stroke patients. Cochrane Database Syst
Rev. 2009;4:CD004433.
7. Wang F, Jia SW. Effect of acupuncture on regional cerebral blood flow
and cerebral functional activity evaluated with single-photon emission computed tomography. Zhongguo Zhong Xi Yi Jie He Za Zhi.
1996;16:340–343.
8. Jia HK, Zhang MJ, Guo YL. Impact of acupuncture on plasmaβ-endogenous
opioid peptide in patients with stroke. Liaolin J Tradit Chin Med. 1995;22:177.
9. Zhao YL, Zhao JW, Wang H. Sequential acupuncture method for treatment of apoplexy hemiplegia and its effects on plasma ET-1 and NO
levels. Zhongguo Zhen Jiu. 2007;27:237–240.
10. Chi XL, Li ZG, Guo ZR, Zhou L, Man HH, Dong CY, et al. Progress of
studies on the mechanism of acupuncture treatment of acute ischemic
cerebral stroke. Zhen Ci Yan Jiu. 2007;32:285–288.
11. Sze FK, Wong E, Or KK, Lau J, Woo J. Does acupuncture improve motor
recovery after stroke? A meta-analysis of randomized controlled trials.
Stroke. 2002;33:2604–2619.
12. Park J, Hopwood V, White AR, Ernst E. Effectiveness of acupuncture for
stroke: a systematic review. J Neurol. 2001;248:558–563.
13. Zhang SH, Liu M, Asplund K, Li L. Acupuncture for acute stroke.
Cochrane Database Syst Rev. 2005;2:CD003317.
14. Johansson K, Lindgren I, Widner H, Wiklund I, Johansson BB. Can
sensory stimulation improve the functional outcome in stroke patients?
Neurology. 1993;43:2189–2192.
15. Hu HH, Chung C, Liu TJ, Chen RC, Chen CH, Chou P, et al. A randomized controlled trial on the treatment for acute partial ischemic stroke
with acupuncture. Neuroepidemiology. 1993;12:106–113.
16.Gosman-Hedstrom G, Claessson L, Klingenstierna U, Carlsson J,
Olausson B, Frizell M, et al. Effects of acupuncture treatment on daily
life activities and quality of life. Stroke. 1998;29:2100–2108.
17. Johansson BB, Haker E, von Arbin M, Britton M, Långström G, Terént
A, et al; Swedish Collaboration on Sensory Stimulation After Stroke.
Acupuncture and transcutaneous nerve stimulation in stroke rehabilitation: a randomized, controlled trial. Stroke. 2001;32:707–713.
18. Vickers A, Goyal N, Harland R, Rees R. Do certain countries produce
only positive results? A systematic review of controlled trials. Control
Clin Trials. 1998;19:159–166.
19. Hatano S. Experience from a multicentre stroke register: a preliminary
report. Bull World Health Organ. 1976;54:541–553.
20. Shi XM. “Xing Nao Kai Qiao” needling method formula. In: Shi XM,
ed. Stroke and “Xing Nao Kai Qiao” Needling Method. 1st ed. Tianjing:
Tianjing Science and Technology Publishing Company; 1998:112–117.
21. Zeng XR, Liu M, Wu B, Zhang SH, Rao P, Wu RF, et al. A randomized
controlled trial of acupuncture for acute ischemic stroke: a pilot study.
Chin J Neurol. 2003;36:247–251.
22. Sze FK, Wong E, Yi X, Woo J. Does acupuncture have additional value
to standard poststroke motor rehabilitation? Stroke. 2002;33:186–194.
23. Park J, White AR, James MA, Hemsley AG, Johnson P, Chambers J,
et al. Acupuncture for subacute stroke rehabilitation: a sham-controlled, subject- and assessor-blind, randomized trial. Arch Intern Med.
2005;165:2026–2031. doi: 10.1001/archinte.165.17.2026.
24. Hopwood V, Lewith G, Prescott P, Campbell MJ. Evaluating the efficacy of acupuncture in defined aspects of stroke recovery: a randomised,
placebo-controlled single blind study. J Neurol. 2008;255:858–866. doi:
10.1007/s00415-008-0790-1.
25. Wu P, Mills E, Moher D, Seely D. Acupuncture in poststroke rehabilitation: a systematic review and meta-analysis of randomized trials. Stroke.
2010;41:e171–e179. doi: 10.1161/STROKEAHA.109.573576.
26. Zhang S, Li N, Liu M. Use of acupuncture for stroke in China. Acupunct
Med. 2009;27:146. doi: 10.1136/aim.2009.001669.
27. Shi XM. Efficacy of Xing Nao Kai Qiao acupuncture program in the
2336 cases of stroke. Tianjin J Tradit Chin Med. 1989;6:2–7, 44.
28. Bao T, Cai L, Snyder C, Betts K, Tarpinian K, Gould J, et al. Patientreported outcomes in women with breast cancer enrolled in a dualcenter, double-blind, randomized controlled trial assessing the effect of
acupuncture in reducing aromatase inhibitor-induced musculoskeletal
symptoms. Cancer. 2014;120:381–389. doi: 10.1002/cncr.28352.
29. Moffet HH. Sham acupuncture may be as efficacious as true acupuncture: a systematic review of clinical trials. J Altern Complement Med.
2009;15:213–216. doi: 10.1089/acm.2008.0356.
30. Hróbjartsson A, Gøtzsche PC. Is the placebo powerless? An analysis
of clinical trials comparing placebo with no treatment. N Engl J Med.
2001;344:1594–1602. doi: 10.1056/NEJM200105243442106.
Downloaded from http://stroke.ahajournals.org/ at CONS CALIFORNIA DIG LIB on April 16, 2015
SUPPLEMENTAL MATERIAL
Supplemental methods - Acupoints and needling methods used in this trial
Main acupoints were stimulated in the following sequence: (1) Neiguan: needle were
inserted perpendicularly (1.5-1.4cm in depth) and manipulated with method of “lifting,
thrusting and rotating (180 degrees, 50-60 circles per minute)” according to
“depletion (of essence)” principle of traditional Chinese medicine (TCM). The
needling was repeated for one to three minutes, then needles were kept in situ for 30
minutes. (2) Renzhong: needle was inserted obliquely (towards nasal septum,
0.5-1.0cm depth), manipulated with method of “sparrow-pecking” according to
“depletion” principle. The needling was continued until emergence of lacrimation (in
the pilot study) or intolerance (in the main study). (3) Sanyinjiao: needle was inserted
1.5-3cm in depth, manipulated with method of “gentle lifting and heavy thrusting”
according to “augmentation (of essence)” principle of TCM. The intensity of
stimulation was required to result in three times of involuntary tics of the affected
limb or patient’s intolerance due to distention, numbness or pain. The needle was kept
in situ for 30 minutes during which the manipulation was repeated two or three times.
For the auxiliary acupoints, needling method of “lifting and thrusting” (40-60 times
per minute for one minute) was used for limb acupoints while method of “rotating”
(180 degrees, 40-60 circle per minute for one minute) was used for trunk and scalp
acupoints. All auxiliary acupoints were stimulated according to “neither augmentation
nor depletion of (essence)” principle. The intensity of stimulation was required to be
enough to result in “De-chi” (feeling of distention, numbness) or intolerance or
involuntary tics of limbs. The needle were also required to be kept in situ for 30
minutes during which the manipulation of needle was repeated two or three times.
1
Supplemental tables
Table I Concomitant therapies during scheduled treatment period
Treatments
Antiplatelets
Anticoagulants
Neuroprotectants
Dehydration agents
Hemodilutions
Chinese medications
Physical therapy
Data are n (%).
Acupuncture
(N=427)
361 (84.5)
115 (27.0)
48 (11.2)
179 (42.0)
50 (11.7)
384 (90.0)
83 (19.4)
Control
(N=435)
367 (84.4)
130 (29.9)
58 (13.3)
173 (39.8)
62 (14.3)
383 (88.0)
99 (22.8)
P
0.797
0.294
0.324
0.591
0.244
0.569
0.232
Table II Outcomes of patients receiving acupuncture no less than 10 sessions
Outcomes
Acupuncture
(N=298)
Control
(N=396)
OR, 95%CI
Death or dependency
At three months*
86 (27.1)
137 (33.0)
0.76, 0.55 to 1.04
At six months
57 (19.1)
102 (25.8)
0.68, 047 to 0.98
Death or institutional care†
At three months
25 (7.9)
41 (9.9)
0.78, 0.46 to 1.31
At six months
17 (5.7)
30(7.6)
0.74, 0.40 to 1.37
Death
At three months
7 (2.2)
7 (3.9)
0.56, 0.23 to 1.39
At six months
12 (4.0 )
18 (4.5)
0.88, 0.42 to 1.86
*Data of 317 patients in acupuncture group and 405 patients in control group were
available at three months and included into analysis. †Institutional care indicates that
patients were cared in hospital, nursing home or rehabilitation unit.
2
Supplemental researcher
List of participating hospitals and principal investigators in order of participants
enrolled:
The West China Hospital of Sichuan University: Ming Liu; The First Affiliated
Hospital of Kunming Medical College: Hua Liu; The Integrated Traditional and
Western Medical Centre for Thrombotic Diseases: Wei Wang; The people’s Hospital
of Anyang City: Qingcheng Yang; The People's Hospital of Sichuan Provincial:
Xianrong Zeng. The First Affiliated Hospital of Wenzhou Medical College: Zhao
Han; The people’s Hospital of Xinxiang City: You Chen; The First People's Hospital
of Chengdu City: Ping Rao; The Third Affiliated Hospital of Neimenggu Medical
College: Dong Wang; The Affiliated Hospital of Pinmei Company: Xiaobo Zhu; The
First Hospital of Zhengzhou City: Huiping Zhang; The Third Hospital of Neijiang
City: Jiaguo Sun; The second Hospital of Wen County: Lingdi Wang; The Sixth
Hospital of Chengdu City: Chunjiang Song; The People’s Hospital of Yongchuan
City: Zhengquan Deng; The Traditional Chinese Medical Hospital of Chengdu City:
Di Cao; The people’s Hospital of Wugang City: Peixia Wang; The 363 Hospital of
Chengdu City, Xueying Wu; The People’s Hospital of Wusheng County: Xu Deng;
The Affiliated Hospital of Guiyang Medical College: Lan Chu; The Seventh Hospital
of Chengdu City: Wei Zhong; The Affiliated Hospital of Chuanbai Medical College:
Xiaoming Wang; The Affiliated Hospital of Luzhou Medical College: Zuoxiao Li;
The First People's Hospital of Shaoguan City: Ping Kang; The First Affiliated
Hospital of Shanxi Medical University: Lihua Wei; The Integrated Traditional and
Western Hospital of Shanghai: Fuli Han; The People’s Hospital of Xuchang County:
Yongsheng Zhou; The second Hospital of Chongqing City: Zhiwei Li; The People’s
Hospital of Naxi District: Yunhua Yuan; The People’s Hospital of Xuyong County:
Li Li; The General Policeman’s Hospital of Beijing City: Zhaoyang Cao; The
People’s Hospital of Shifang City: Decai Qian; The Centrals Hospital of Mianyang
City: Youjun Feng; The Centrals Hospital of Panzhihua City: Ling Yang; The
People’s Hospital of An County: Youping Zhang; The Affiliated Hospital of Chengdu
Traditional Chinese Medicine University: Fuyou Liu; The Second Affiliated Hospital
of Jiangxi Medical College: Liying Deng; The People’s Hospital of Meitan County:
Yongfu Wang; The People’s Hospital of Longchang County: Tingnian Yan; The First
Affiliated Hospital of Xi’an Jiaotong University: Chengbin Wu; The Traditional
Chinese Medical Hospital of Guangyuan City: Gang He.
3
Acupuncture Efficacy on Ischemic Stroke Recovery: Multicenter Randomized Controlled
Trial in China
Shihong Zhang, Bo Wu, Ming Liu, Ning Li, Xianrong Zeng, Hua Liu, Qingcheng Yang, Zhao
Han, Ping Rao and Dong Wang
Stroke. published online April 14, 2015;
Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 2015 American Heart Association, Inc. All rights reserved.
Print ISSN: 0039-2499. Online ISSN: 1524-4628
The online version of this article, along with updated information and services, is located on the
World Wide Web at:
http://stroke.ahajournals.org/content/early/2015/04/13/STROKEAHA.114.007659
Data Supplement (unedited) at:
http://stroke.ahajournals.org/content/suppl/2015/04/14/STROKEAHA.114.007659.DC1.html
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published
in Stroke can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office.
Once the online version of the published article for which permission is being requested is located, click
Request Permissions in the middle column of the Web page under Services. Further information about this
process is available in the Permissions and Rights Question and Answer document.
Reprints: Information about reprints can be found online at:
http://www.lww.com/reprints
Subscriptions: Information about subscribing to Stroke is online at:
http://stroke.ahajournals.org//subscriptions/
Downloaded from http://stroke.ahajournals.org/ at CONS CALIFORNIA DIG LIB on April 16, 2015