Accepted Manuscript Title: Moxibustion for Essential Hypertension Author: Xingjiang Xiong Wei Liu Xiaochen Yang Bo Feng Jie Wang PII: DOI: Reference:
S0965-2299(13)00190-8 http://dx.doi.org/doi:10.1016/j.ctim.2013.11.005 YCTIM 1275
To appear in:
Complementary Therapies in Medicine
Received date: Revised date: Accepted date:
8-7-2013 11-11-2013 18-11-2013
Please cite this article as: Xiong X, Liu W, Yang X, Feng B, Wang J, Moxibustion for Essential Hypertension, Complementary Therapies in Medicine (2013), http://dx.doi.org/10.1016/j.ctim.2013.11.005 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Moxibustion for Essential Hypertension∗
1 2
Xingjiang Xiong1, Wei Liu1, Xiaochen Yang1, Bo Feng1, Jie Wang1
3
ip t
4 1. Department of Cardiology, Guang′anmen Hospital, China Academy of Chinese Medical
6
Sciences, Beijing 100053, China
cr
5
us
7 8
an
9
M
10 11
d
12
Ac ce pt e
13 14 15 16 17 18 19 20 ∗
Corresponding author at: Department of Cardiology, Guang′anmen Hospital, China Academy of Chinese Medical Sciences, Beixiange 5#, Xicheng District, Beijing 100053, China. Tel.: +86 1088001817; fax: +86 1088001229. E-mail addresses:
[email protected] (X. Xiong) 1
Page 1 of 27
1 2
Abstract: The objective of this review was to assess the current clinical evidence of moxibustion for essential hypertension (EH). 7 electronic databases were searched until March, 2013. Randomized
4
clinical trials testing moxibustion, or combined with antihypertensive drugs, against
5
antihypertensive drugs alone were included. Study selection, data extraction, quality assessment,
6
and data analyses were conducted according to the Cochrane standards. Finally, 5 randomized
7
trials were included. The methodological quality of the included trials was evaluated as generally
8
low. As compared to antihypertensive drugs, no positive results in BP (RR: 1.19 [0.50, 2.81]; P =
9
0.70), was found about moxibustion. However, when combined with antihypertensive drugs,
an
us
cr
ip t
3
positive results in SBP (WMD: -9.57 [-10.80, -8.34]; P < 0.00001), DBP (WMD: -4.08 [-4.60,
11
-3.56]; P < 0.00001), and BP (RR: 3.35 [1.03, 10.89]; P = 0.04) were found about moxibustion
12
plus antihypertensive drugs. Most of the trials did not report adverse events, and the safety of
13
moxibustion is still uncertain. Therefore, no confirm conclusion about the effectiveness and safety
14
of moxibustion as adjunctive treatment for EH could be made. Rigorously designed trials are
15
needed to confirm the evidence.
d
Ac ce pt e
16
M
10
17
Key Words:
18
moxibustion; essential hypertension; systematic review
19 20 21 22 2
Page 2 of 27
1
1. Introduction
2 In 1914, Fisher discovered a relationship between high blood pressure (BP) and mortality
4
among life-insurance applicants [1]. Despite this long history of awareness, hypertension remains
5
one of the major risk factors for cardiovascular diseases (CVDs), with an enormous burden on
6
health care resources and the community throughout the world [2]. Across World Health
7
Organization regions, approximately 62% of strokes and 49% of myocardial infarctions are caused
8
by high BP [3]. It has been identified as the leading risk factor for mortality, and is ranked third as
9
a cause of disability-adjusted life-years [4-5]. Therefore, hypertension and blood-pressure-related
10
disease have become an emerging epidemic and important worldwide public-health challenge,
11
especially in most low-income and middle-income countries, including China, where there is
12
generally poor awareness, treatment, and control of the condition [6-9]. Recently, it was confirmed
13
that a reduction of 5 mmHg in systolic blood pressure (SBP) has been associated with a 7%
14
reduction in all-cause mortality [10-11]. A challenge faced by all countries is how to effectively
15
reduce the harmful impact of hypertension on public health. For a long time, strategies to manage
16
hypertension have been mainly dependent on the use of antihypertensive drugs. However,
17
effective treatment of hypertension is limited by availability, cost, and adverse effects of
18
conventional western medicine treatment, and these improvements have not been extended to the
19
total population [12]. Approximately 30% of individuals with hypertension, however, may still be
20
unaware of their condition, more than 40% of individuals with hypertension are not on treatment,
21
and among those with diagnosed hypertension, treatment is frequently inadequate, two thirds of
22
hypertensive patients are not being controlled to BP levels < 140/90 mm Hg [13]. A certain
Ac ce pt e
d
M
an
us
cr
ip t
3
3
Page 3 of 27
proportion of hypertensive patients still suffered from hypertension related symptom including
2
severe headache, dizziness, fatigue, etc. Therefore, some of them have turned to complementary
3
and alternative medicine (CAM) [14-18], including traditional Chinese medicine (TCM) [19-29],
4
for lowing BP and improving its related symptoms [30-36].
5
ip t
1
Moxibustion, a traditional medical intervention of TCM, involves the application of ignited
mugwort (Artemisia vulgaris) directly or indirectly at acupuncture points or other specific parts of
7
the body to treat or prevent diseases [37-39]. The mechanism of moxibustion maybe related to the
8
combination of heat (burning pain and heat stress), tar (extract), aroma (fume) and psychological
9
stress [40-41]. According to the theory of TCM, a possible explanation for how moxibustion
an
us
cr
6
works is that heat could increase qi circulation and relieve qi stagnation by stimulating
11
acupuncture points to regulate the function of meridians and visceral organs [42]. Currently, there
12
has been a growing interest and prevalence in moxibustion worldwide [43-44]. Previous
13
researches indicated that moxibustion may improve health-related fitness, quality of life, and
14
psychological well-being [45]. Recent studies also suggest that it may have beneficial effects for
15
patients with hypertension [46-48]. It is found out that moxibustion could contribute to lowing BP
16
smoothly, restoring the circadian rhythm of BP, and improving symptoms and signs especially
17
[49-50]. Mechanisms of moxibustion for hypertension maybe related to regulating oxygen free
18
radical system and endocrine function of vascular endotheliocytes [51-52]. Currently, efficacy of
19
moxibustion for essential hypertension (EH) is confirmed by a large number of published case
20
series and randomized trials [46, 49, 53-56]. Moxibustion used alone or combined with
21
antihypertensive drugs has been widely used as adjunctive treatment for EH. And until now, there
22
is one published systematic review (SR) about moxibustion for EH in English [57]. However, as
Ac ce pt e
d
M
10
4
Page 4 of 27
moxibustion was mainly used and researched in China, only 1 Chinese database, just Chinese
2
National Knowledge Infrastructure (CNKI), was searched in the above SR. The other three main
3
databases in Chinese were not included to retrieve the maximum possible number of trials of
4
moxibustion for EH. Therefore, the role of moxibustion is still unclear due to different search
5
strategies and databases. This study aims to assess the current clinical evidence of moxibustion as
6
adjunctive treatment for EH.
cr
ip t
1
8
us
7
2. Methods
12
M
11
2.1. Database and Search Strategies.
Literature searches were conducted in Chinese Scientific Journal Database (VIP), Chinese
d
10
an
9
Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI),
14
Wanfang data, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane
15
Library (March, 2013), EMBASE, and PubMed. We also searched the reference list of retrieved
16
papers. As moxibustion is mainly used and researched in China, four major databases in Chinese
17
were all searched to retrieve the maximum possible number of trials of moxibustion for EH. All of
18
those searches ended on 18 March, 2013. Ongoing registered clinical trials were searched in the
19
website of Chinese clinical trial registry (http://www.chictr.org/) and international clinical trial
20
registry by U.S. national institutes of health (http://clinicaltrials.gov/). The following search terms
21
were used individually or combined: ‘hypertension’, ‘essential hypertension’, ‘moxibustion’,
22
‘clinical trial’, and ‘randomized controlled trial’. The bibliographies of included studies were
Ac ce pt e
13
5
Page 5 of 27
1
searched for additional references.
2 3
2.2. Inclusion Criteria.
5
ip t
4 All the parallel randomized controlled trials (RCTs) of moxibustion compared with
antihypertensive drugs or no treatment in patients with hypertension were included. RCTs
7
combined moxibustion with antihypertensive drugs compared with antihypertensive drugs were
8
included as well. There were no restrictions on population characteristics, language and
9
publication type. The main outcome measure was BP. Duplicated publications reporting the
13 14
us
an
M
12
2.3. Data Extraction and Quality Assessment.
d
11
same groups of participants were excluded.
Ac ce pt e
10
cr
6
Two authors conducted the literature searching (X. J. Xiong, X. C. Yang), study selection (X.
15
J. Xiong, B. Feng), and data extraction (X. J. Xiong, W. Liu) independently. The extracted data
16
included authors, title of study, year of publication, study size, age and sex of the participants,
17
details of methodological information, treatment process, details of the control interventions,
18
outcomes, and adverse effects for each study. Disagreement was resolved by discussion and
19
reached consensus through a third party (J. Wang).
20
The methodological quality of trials was assessed independently using criteria from the
21
Cochrane Handbook for Systematic Review of Interventions, Version 5.1.0 (X. J. Xiong, B. Feng)
22
[58]. The items included random sequence generation (selection bias), allocation concealment 6
Page 6 of 27
(selection bias), blinding of participants and personnel (performance bias), blinding of outcome
2
assessment (detection bias), incomplete outcome data (attrition bias), selective reporting (reporting
3
bias), and other bias. The quality of all the included trials was categorized to low/unclear/high risk
4
of bias (“Yes” for a low of bias, “No” for a high risk of bias, “Unclear” otherwise). Then trials
5
were categorized into three levels: low risk of bias (all the items were in low risk of bias), high
6
risk of bias (at least one item was in high risk of bias), unclear risk of bias (at least one item was in
7
unclear).
us
cr
ip t
1
8 2.4. Data Synthesis.
an
9
M
10
Revman 5.1 software provided by the Cochrane Collaboration was used for data analyses.
12
Dichotomous data were presented as risk ratio (RR) and continuous outcomes as mean difference
13
(MD), both with 95% confidence interval (CI). Heterogeneity was recognized significant when I2
14
≥ 50%. Fixed effects model was used if there is no significant heterogeneity of the data; random
15
effects model was used if significant heterogeneity existed (50% < I2 < 85%). Publication bias
16
would explored by funnel plot analysis if sufficient studies were found.
18
Ac ce pt e
17
d
11
3. Result
19 20
3.1.Description of Included Trials.
21 22
A flow chart depicted the search process and study selection (as shown in Figure 1). After 7
Page 7 of 27
primary searches from the databases, 318 articles were screened. After reading the titles and
2
abstracts, 280 articles of them were excluded for obviously not meeting the inclusive criteria
3
(including literature reviews, nonclinical studies, and case series). Full texts of 38 articles were
4
retrieved, and 33 articles were excluded with reasons listed as the following: participants did not
5
meet the inclusive criteria (n = 21), duplication (n = 3), no control group (n = 4), the intervention
6
included other treatment (n = 3), and no data for extraction (n = 2). Finally, 5 RCTs [59-63] were
7
included. All the RCTs were published in Chinese. The characteristics of included trials were
8
listed in Table 1.
us
cr
ip t
1
357 patients with EH were included. 5 trials specified two diagnostic criteria of hypertension,
10
4 trials [59-62] used 1999 WHO -ISH guidelines for the management of hypertension (1999 WHO
11
-ISH GMH); 1 trial [63] used Chinese Guidelines for the Management of Hypertension-2004
12
(CGMH-2004). Interventions included moxibustion alone, or combined with antihypertensive
13
drugs. The controls included routine antihypertensive drugs. 2 trials [60, 61] investigated
14
moxibustion using alone versus antihypertensive drugs (including maleate enalapril and
15
amlodipine besylate). 3 trials [59, 62, 63] investigated moxibustion combined with
16
antihypertensive drugs versus antihypertensive drugs (including amlodipine besylate, Beijing
17
hypotensive No.0, etc.). The total treatment duration ranged from 10 to 30 days. All of the 5 trials
18
used the BP as the outcome measure.
Ac ce pt e
d
M
an
9
19 20
3.2. Methodological Quality of Included Trials.
21 22
The majority of the included trials were assessed to be of general poor methodological 8
Page 8 of 27
quality according to the predefined quality assessment criteria (Table 2). The randomized
2
allocation of participants was mentioned in all trials; however, only 1 trial stated the methods for
3
sequence generation with stratified sampling [59]. Insufficient information greatly limited us to
4
judge whether or not it was conducted properly. Allocation concealment, blinding of participants
5
and personnel, and blinding of outcome assessment were not mentioned in all trials. No trial
6
reported drop-out. None of trials had a pre-trial estimation of sample size. We tried to contact the
7
author for further information, however, no information has been provided to date.
us
cr
ip t
1
8 3.3.Effect of the Interventions
an
9
11
M
10
All the included trials compared moxibustion, or combined with antihypertensive drugs with antihypertensive drugs alone. A change in BP was reported in all the trials. According to the
13
different interventions, it could be divided into 2 subgroups, including “moxibustion versus
14
antihypertensive drugs” and “moxibustion plus antihypertensive drugs versus antihypertensive
15
drugs”.
17 18 19
Ac ce pt e
16
d
12
3.3.1. Moxibustion versus antihypertensive drugs
2 trial [60, 61] used three classes to evaluate treatment effects on BP: significant effective
20
(DBP decreased by 10 mmHg reaching the normal range, or, DBP has not yet returned to normal,
21
but has been reduced ≥ 20mmHg), effective (DBP decreased to less than 10mmHg reaching the
22
normal range, or, DBP decreased by 10-19 mmHg, but did not reach the normal range, or, SBP 9
Page 9 of 27
1
decreased ≥ 30mmHg), and ineffective (Not to meet the above standards). The trial showed no
2
significant difference between treatment and control group (RR: 1.19 [0.50, 2.81]; P = 0.70)
3
(Table 3).
5
3.3.2. Moxibustion plus antihypertensive drugs versus antihypertensive drugs.
cr
6
ip t
4
2 trials [62, 63] used three classes to evaluate treatment effects on BP. The trials showed
8
significant difference between treatment and control group (RR: 3.35 [1.03, 10.89]; P = 0.04)
9
(Table 3).
an
When it comes to SBP, 1 trial [59] showed no applicable heterogeneity in the result. Thus,
M
10
us
7
fixed-effects model was used for statistical analysis. The meta-analysis showed there is significant
12
beneficial effect on the combination group compare to antihypertensive drugs group (WMD: -9.57
13
[-10.80, -8.34]; P < 0.00001) (Table 4).
Ac ce pt e
14
d
11
When it comes to DBP, it [59] showed no applicable heterogeneity in the result. Thus,
15
fixed-effects model was used for statistical analysis. The meta-analysis showed there is significant
16
beneficial effect on the combination group compare to antihypertensive drugs group (WMD: -4.08
17
[-4.60, -3.56]; P < 0.00001) (Table 5).
18 19
3.4. Publication Bias. The number of trials was too small to conduct any sufficient additional
20
analysis of publication bias.
21 22
3.5. Adverse Effect. Only 1 trial mentioned the adverse effect [63]. No specific symptoms and 10
Page 10 of 27
1
signs were found about moxibustion in the trial. The other 4 trials [59-62] didn’t report it at all.
2 3
4. Discussion
5
ip t
4 This study aims to assess the current clinical evidence of moxibustion for EH. In this review, as compared to antihypertensive drugs, moxibustion showed similar beneficial effect for
7
hypertension therapy; however, as adjunctive treatment, moxibustion combined with
8
antihypertensive drugs showed more beneficial effect than antihypertensive drugs alone for EH.
9
Although meta-analysis showed positive results, no confirm conclusion about the effectiveness
an
us
cr
6
and safety of moxibustion as adjunctive treatment for EH could be made based on the current
11
evidence due to the small sample size, and poor methodological qualities of included trials. The
12
following limitations of this review should be considered.
d
Firstly, the methodological quality of the included RCTs is generally low. In our review, in
Ac ce pt e
13
M
10
14
fact, it was impossible to find well-designed trials to evaluate efficacy of moxibustion for the
15
management of EH. All the included trials had risk of bias in terms of design, reporting, and
16
methodology. Inadequate reporting of study design, allocation sequence, allocation concealment,
17
blinding, intention to treat analysis and drop outs were provided in the majority of trials. There
18
was no definite, double blind RCTs with clear method. Randomization was mentioned but without
19
further details in most trials, which do limit a proper judgment about how the RCTs were
20
conducted. As no detailed information about allocation concealment could be got in all the trials,
21
the claimed RCTs maybe not real RCTs actually. In our opinion, the credibility of current clinical
22
evidence could be weakened and potential selection bias might be generated. Also, no trials have 11
Page 11 of 27
reported double-blind (both blinding of participants and personnel and blinding of outcome
2
assessment), which would directly lead to the performance bias and detection bias. We understood
3
that it is the common problem lied in all TCM researches. Perhaps certain features associated with
4
moxibustion such as research conditions, funding and the characterization of therapy did limit the
5
clinical usage of double-blind. No trial reported drop-out. And most of the trials haven’t reported
6
intention to treat analysis. Additionally, most of the trials were small sample size and single-center.
7
None of the trials have reported the sample size estimation, which placed the statistical analysis’s
8
validity in doubt. Thus, whether sample size meets the requirement of the trial is still unknown. If
9
poorly designed, all the trials would show larger differences compared with well designed trials.
an
us
cr
ip t
1
Secondly, adverse effect of moxibustion has been attracted more and more attention
11
worldwide [64]. With increasing awareness of self-care, no drug therapy and natural plants as
12
complementary therapies are favored by people worldwide for their advantages in preventing and
13
curing diseases. It is widely accepted that they are relative safe for various diseases in China
14
[65]. However, with more and more reporting on the safety problem of complementary therapies,
15
it has hence become an important focus of this systematic review [66]. In this review, there was a
16
lack of knowledge for the reporting adverse effect of moxibustion. 4 out of 5 trials did not report
17
the adverse effect of moxibustion at all. And only 1 trial reported adverse effect without severe
18
symptoms and signs. Therefore, a conclusion about the safety of moxibustion cannot be made
19
clearly. It needs to be monitored rigorously and reported appropriately in the future clinical trials.
20
Thirdly, publication biases may play an important role in the review. After conducting
21
comprehensive literature searches, only trials conducted in China could be got. We tried to avoid
22
language bias and location bias; however, potential publication bias could not be excluded
Ac ce pt e
d
M
10
12
Page 12 of 27
1
completely. We have conducted extensive searches for unpublished material, but no trials were
2
found. In conclusion, the results of the trials included in this SR are likely to be biased by many
4
factors due to the poor methodological qualities. The reported beneficial effect of moxibustion for
5
lowering BP in hypertensive patients should be interpreted cautiously. Therefore, no confirm
6
conclusion about the effectiveness and safety of moxibustion as adjunctive treatment for EH could
7
be made.
cr us
9
To pave the evidence-based clinical practice, future rigorously designed randomized trials should overcome these limitations. Great attention should be paid to the following methodological
an
8
ip t
3
issues: (1) properly implementing randomization (random sequence generation and allocation
11
concealment); (2) appropriate methods used in double-blind (blinding of participants and
12
personnel and blinding of outcome assessment); (3) strictly reporting dropout and intention to treat
13
analysis; (4) attaching importance to pre-trial estimation of sample size and long-term follow-up;
14
(5) rigorously monitoring and reporting adverse effect; (6) comprehensively reporting of the RCTs
15
according to the recommendations of the CONSORT Statement [67]. We hope that with
16
increasing publication of high-qualified trials, more convincing clinical evidence would confirm
17
or refute the results.
19 20
d
Ac ce pt e
18
M
10
Conflicts of Interests
All authors declare that they have no conflicts of interests.
21 22
Acknowledgment
23
The current work was partially supported by the National Basic Research Program of China (973 13
Page 13 of 27
1
Program, No. 2003CB517103) and the National Natural Science Foundation Project of China (No.
2
90209011). The funders had no role in study design, data collection and analysis, decision to
3
publish, or preparation of the manuscript.
ip t
4
References
6
[1] J. W. Fisher, “The diagnostic value of the sphygmomanometer in examinations for life insurance,” JAMA, vol. 63, pp. 1752-1754, 1914.
us
7
cr
5
[2] G. Mancia, G. De Backer, A. Dominiczak, R. Cifkova, R. Fagard, G. Germano, et al,
9
“Guidelines for the management of arterial hypertension: the task force for the management
10
of arterial hypertension of the European Society of Hypertension (ESH) and of the European
11
Society of Cardiology (ESC),” J Hypertens, vol. 25, pp. 1105-1187, 2007.
14 15
M
d
13
[3] M. A. Alderman and T. Ogihara, “Global challenge for overcoming high blood pressure: fukuoka statement,” J Hypertens, vol. 25, pp. 727, 2007.
Ac ce pt e
12
an
8
[4] M. Ezzati, A. D. Lopez, A. Rodgers, H. S. Vander, and C. J. Murray, “Selected major risk factors and global and regional burden of disease,” Lancet, vol. 360, pp. 1347-1360, 2002.
16
[5] P. M. Kearney, M. Whelton, K. Reynolds, P. Muntner, P. K. Whelton, and J. He, “Global
17
burden of hypertension: analysis of worldwide data,” Lancet, vol. 365, pp. 217-23, 2005.
18
[6] X. J. Xiong, X. C. Yang, Y. M. Liu, Y. Zhang, P. Q. Wang, and J. Wang, “Chinese herbal
19
formulas for treating hypertension in traditional Chinese medicine: perspective of modern
20
science,” Hypertension Research, vol. 36, pp. 570-579, 2013.
21 22
[7] D. Yach, C. Hawkes, C. L. Gould, and K. J. Hofman, “The global burden of chronic diseases: overcoming impediments to prevention and control,” JAMA, vol. 291, pp. 2616-2622, 2004. 14
Page 14 of 27
1 2
[8] S. Yusuf, S. Reddy, S. Ôunpuu, and S. Anand, “Global burden of cardiovascular diseases,” Circulation, vol. 104, pp. 2855-2864, 2001. [9] C. M. Lawes, S. V. Hoorn, A. Rodgers, and for the International Society of Hypertension,
4
“Global burden of blood-pressure-related disease, 2001,” Lancet, vol. 371, pp. 1513-18,
5
2008.
ip t
3
[10] A. V. Chobanian, G. L. Bakris, H. R. Black, W. C. Cushman, L. A. Green, J. L. Izzo, et al,
7
“Seventh report of the joint national committee on prevention, detection, evaluation, and
8
treatment of high blood pressure,” Hypertension, vol. 42, pp. 1206-1252, 2003.
us
cr
6
[11] P. K. Whelton, J. He, L. J. Appel, J. A. Cutler, S. Havas, T. A. Kotchen, et al, “Primary
10
prevention of hypertension: clinical and public health advisory from the National High Blood
11
Pressure Education Program,” JAMA, vol. 288, no. 15, pp. 1882-1888, 2002.
M
123, pp. 2892-2896, 2011.
d
13
[12] K. Sliwa, S. Stewart, and B. J. Gersh, “Hypertension: a global perspective,” Circulation, vol.
Ac ce pt e
12
an
9
14
[13] T. Krause, K. Lovibond, M. Caulfield, T. McCormack, B. Williams, and Guideline
15
Development Group, “Management of hypertension: summary of NICE guidance,” BMJ, vol.
16
343, pp. d4891, 2011.
17
[14] X. J. Xiong and J. Wang, “Evidence-based Chinese Medicine for Hypertension,”
18
Evidence-Based Complementary and Alternative Medicine, vol. 2013, Article ID 978398, pp.
19 20 21 22
1-12, 2013. [15] E. Ernst, “Complementary/alternative medicine for hypertension: a mini-review,” Wien Med Wochenschr, vol. 123, pp. 386-391, 2005. [16] H. Xu and K. J. Chen, “Complementary and alternative medicine: is it possible to be 15
Page 15 of 27
1 2 3
mainstream?,” Chinese Journal of Integrative Medicine, vol. 18, no. 6, pp. 403-404, 2012. [17] R. Nahas, “Complementary and alternative medicine approaches to blood pressure reduction: an evidence-based review,” Can Fam Physician, vol. 54, pp. 1529-1533, 2008. [18] X. J. Xiong, X. C. Yang, W. Liu, et al, “Banxia baizhu tianma decoction for essential
5
hypertension: a systematic review of randomized controlled trials,” Evidence-Based
6
Complementary and Alternative Medicine, vol. 2012, Article ID 271462, 2012.
cr
ip t
4
[19] T. P. Lam and K. S. Sun, “Dilemma of integration with Western medicine – Views of
8
Traditional Chinese Medicine practitioners in a predominant Western medical setting,”
9
Complementary Therapies in Medicine, vol. 21, no. 4, pp. 300-305, 2013.
an
us
7
[20] X. J. Xiong, F. Y. Chu, H. X. Li, and Q.Y. He, “Clinical application of the TCM classic
11
formulae for treating chronic bronchitis,” Journal of Traditional Chinese Medicine, vol. 31,
12
no. 1, pp. 69-72, 2011.
d
M
10
[21] A. H. Zhang, H. Sun, P. Wang, Y. Han, and X. J. Wang, “Future perspectives of personalized
14
medicine in traditional Chinese medicine: A systems biology approach,” Complementary
15 16 17 18
Ac ce pt e
13
Therapies in Medicine, vol. 20, pp. 93-99, 2012.
[22] K. J. Chen, K. K. Hui, M. S. Lee, and H. Xu, “The potential benefit of complementary/alternative
medicine
in
cardiovascular
diseases,”
Evidence-Based
Complementary and Alternative Medicine, vol. 2012, Article ID 125029, 1 pages, 2012.
19
[23] J. Wang, P. Q. Wang, and X. J. Xiong, “Current situation and re-understanding of syndrome
20
and formula syndrome in Chinese medicine,” Internal Medicine, 2012, vol. 2, Article ID
21
1000113, 1-5.
22
[24] K. Templeman, and A. Robinson, “Integrative medicine models in contemporary primary 16
Page 16 of 27
1
health care,” Complementary Therapies in Medicine, vol. 19, no. 2, pp. 84-92, 2011. [25] J. Wang and X. J. Xiong, “Current situation and perspectives of clinical study in integrative
3
medicine in China,” Evidence-Based Complementary and Alternative Medicine, vol. 2012,
4
Article ID 268542, 11 pages, 2012.
ip t
2
[26] X. P. Chen, L. X. Pei, and J. J. Lu, “Filling the gap between traditional Chinese medicine and
6
modern medicine, are we heading to the right direction?,” Complementary Therapies in
7
Medicine, vol. 21, no. 3, pp. 272-275, 2013.
us
9
[27] H. Xu and K. J. Chen, “Integrative medicine: the experience from China,” Journal of Alternative and Complementary Medicine, vol. 14, no. 1, pp. 3-7, 2008.
an
8
cr
5
[28] X. J. Xiong, X. C. Yang, W. Liu, F. Y. Chu, P. Q. Wang, and J. Wang, “Trends in the
11
treatment of hypertension from the perspective of traditional Chinese medicine,”
12
Evidence-Based Complementary and Alternative Medicine, vol. 2013, Article ID 275279, 13
13
pages, 2013.
Ac ce pt e
d
M
10
14
[29] J. H. Zhang, B. Wider, H. C. Shang, X. M. Li, and E. Ernst, “Quality of herbal medicines:
15
Challenges and solutions,” Complementary Therapies in Medicine, vol. 20, pp. 100-106,
16
2012.
17
[30] J. Wang and X. J. Xiong, “Control strategy on hypertension in Chinese medicine,”
18
Evidence-Based Complementary and Alternative Medicine, vol. 2012, Article ID 284847, 6
19
pages, 2012.
20
[31] M. S. Lee, H. J. Lim, and M. S. Lee, “Impact of qigong exercise on self-efficacy and other
21
cognitive perceptual variables in patients with essential hypertension,” The Journal of
22
Alternative and Complementary Medicine, vol. 10, no. 4, pp. 675-680, 2004. 17
Page 17 of 27
[32] J. Wang, K. W. Yao, X. C. Yang, W. Liu, B. Feng, J. Z. Ma, X. L. Du, P. Q. Wang, and X. J.
2
Xiong, “Chinese patent medicine liu wei di huang wan combined with antihypertensive drugs,
3
a new integrative medicine therapy, for the treatment of essential hypertension: a systematic
4
review of randomized controlled trials,” Evidence-Based Complementary and Alternative
5
Medicine, vol. 2012, Article ID 714805, 7 pages, 2012.
ip t
1
[33] M. S. Lee, T. Y. Choi, B. C. Shin, J. I. Kim, and S. S. Nam, “Cupping for hypertension: a
7
systematic review,” Clinical and Experimental Hypertension, vol. 32, no. 7, pp. 423-425,
8
2010.
us
cr
6
[34] J. Wang and X. J. Xiong, “Outcome measures of Chinese herbal medicine for hypertension:
10
an overview of systematic reviews,” Evidence-Based Complementary and Alternative
11
Medicine, vol. 2012, Article ID 697237, 10 pages, 2012.
M
d
13
[35] M. S. Lee, M. Pittler, R. L. Guo, and E. Ernst, “Qigong for hypertension: a systematic review of randomized clinical trials,” Journal of Hypertension, vol. 25, no. 8, pp. 1525-1532, 2007.
Ac ce pt e
12
an
9
14
[36] J. Wang, B. Feng, X. C. Yang, W. Liu, F. Teng, S. Li, and X. J. Xiong, “Tai Chi for Essential
15
Hypertension,” Evidence-Based Complementary and Alternative Medicine, vol. 2013, Article
16 17 18
ID 215254, 10 pages, 2013.
[37] R. M. Yan, “The origin and development of chinese acupuncture and moxibustion,” Ancient Science of Life, vol. IV, no. 4, pp. 224-228, 1985.
19
[38] S. Y. Kim, Y. Chae, S. M. Lee, H. Lee, and H. J. Park, “The effectiveness of moxibustion: an
20
overview during 10 years,” Evidence-Based Complementary and Alternative Medicine, vol.
21
2011, Article ID 306515, 19 pages, 2011.
22
[39] X. Y. Gao, C. Y. Chong, S. P. Zhang, K. W. E. Cheng, and B. Zhu, “Temperature and Safety 18
Page 18 of 27
Profiles of Needle-Warming Techniques in Acupuncture and Moxibustion,” Evidence-Based
2
Complementary and Alternative Medicine, vol. 2012, Article ID 168393, 6 pages, 2012.
3
[40] H. Yamashita, Y. Ichiman, and Y. Tanno, “Changes in peripheral lymphocyte subpopulations
4
after direct moxibustion,” The American Journal of Chinese Medicine, vol. 29, pp. 227–235,
5
2001.
8 9
cr
Taiwan,” Chin J Integr Med, vol. 17, no. 3, pp. 177-186, 2011.
us
7
[41] J. G. Lin, and Y. H. Chen, “The mechanistic studies of acupuncture and moxibustion in
[42] M. S. Lee, J. W. Kang, and E. Ernst, “Does moxibustion work? an overview of systematic reviews,” BMC Research Notes, no. 3, pp. 284, 2010.
an
6
ip t
1
[43] K. Kawakita, T. Shichidou, E. Inoue, et al., “Do Japanese Style Acupuncture and
11
Moxibustion Reduce Symptoms of the Common Cold?,” Evidence-Based Complementary
12
and Alternative Medicine, vol. 5, no. 4, pp. 481-489, 2008. doi:10.1093/ecam/nem055
d
M
10
[44] R. Chen, M. Chen, J. Xiong, et al., “Is There Difference between the Effects of Two-Dose
14
Stimulation for Knee Osteoarthritis in the Treatment of Heat-Sensitive Moxibustion?,”
15 16 17 18 19 20
Ac ce pt e
13
Evidence-Based Complementary and Alternative Medicine, vol. 2012, Article ID 696498, 7
pages, 2012. doi:10.1155/2012/696498.
[45] J. H. Chiu, “How does moxibustion possibly work?,” Evidence-Based Complementary and Alternative Medicine, vol. 2013, Article ID 198584, 8 pages, 2013.
[46] Y. S. Zhang, “Ginger-separated moxibustion of Guanyuan point for treatment of 117 cases of primary hypertension,” World J. Acup-Mox, vol. 11, no. 1, pp. 48-50, 2001.
21
[47] Y. H. Guo, X. F. Zhao, and S. Wang, “Discussion on clinical trial design of treatment of
22
hypertension with acupuncture and moxibustion,” Zhongguo Zhen Jiu, vol. 31, no. 2, pp. 19
Page 19 of 27
1
177-180, 2011. [48] K. M. Shin, J. E. Park, Y. Liu, et al., “Efficacy of moxibustion for pre- or stage I
3
hypertension: study protocol for a pilot randomized controlled trial,” Trials, vol. 13, pp. 188,
4
2012.
6
[49] X. N. Wu and R. Qian, “The effects of moxibustion on circadian rhythm of blood pressure in essential hypertensive patients,” Zhongguo Min Zu Min Jian Yi Yao, vol. 19, pp. 9-10, 2011.
cr
5
ip t
2
[50] S. H. Cho, “Effects of moxibustion on physiological indices and autonomic nervous
8
symptoms in adults with prehypertension,” J Korean Acad Nurs, vol. 40, no. 5, pp. 686-694,
9
2010.
an
us
7
[51] L. H. Peng, L. M. Feng, Z. F. Chen, etc, “Effects of moxibustion on blood pressure, NO, ET,
11
SOD and MDA in the patient of hypertension,” Zhongguo Zhen Jiu, vol. 24, no. 3, pp.
12
157-159, 2004.
d
M
10
[52] C. N. Jin, T. S. Zhang, L. X. Ji, and Y. F. Tian, “Survey of studies on mechanisms of
14
acupuncture and moxibustion in decreasing blood pressure,” Zhongguo Zhen Jiu, vol. 27, no.
15
Ac ce pt e
13
6, pp. 467-470, 2007.
16
[53] G. M. Wang, F. Y. Wen, L. X. Li, and Y. Q. Song, “Clinical observation of 178 cases of
17
primary hypertension treated by scar moxibustion,” Zhongguo Zhong Yi Yao Xin Xi Za Zhi,
18 19 20
vol. 13, no. 1, pp. 55, 2006.
[54] H. Z. Cao, “Clinical observation on hypertension treated with combination of TCM and western medicine,” Heilongjiang Yi Xue, vol. 32, no. 9, pp. 684, 2008.
21
[55] N. Wang, K. Zhang, and J. Zheng, “Clinical observation of 30 cases of primary hypertension
22
with liver yang hyperactivity syndrome treated by moxibustion,” Sichuan Zhong Yi, vol. 25, 20
Page 20 of 27
1
no. 4, pp. 60-61, 2007. [56] X. Zhang and W. Peng, “Clinical observation of 47 cases of primary hypertension with
3
stagnation of phlegm-stasis syndrome treated by moxibustion,” Zhongguo Zhen Jiu, vol. 29,
4
no. 12, pp. 966, 2009.
cr
7
systematic review,” BMC Cardiovascular Disorders, vol. 10, 2010.
[58] J. P. T. Higgins and S. Green, “Cochrane handbook for systematic reviews of interventions,
8
version
5.1.0
[updated
March
9
http://www.cochrane-handbook.org/.
2011],”
The
us
6
[57] J. I. Kim, J. Y. Choi, H. Lee, M. S. Lee, and E. Ernst, “Moxibustion for hypertension: a
Cochrane
Collaboration,
2009,
an
5
ip t
2
[59] S. Zhang, Y. Su, M. Wan, X. X. Hu, Q. Q. Guo, and W. Y. Li, “Therapeutic effect of
11
moxibustion at heat-sensitive points for primary hypertension: an observation of 34 cases,”
12
Xin Zhong Yi, vol. 43, no. 8, pp. 131-133, 2011.
14
d
[60] R. X. Jin, Y. Liu, and S. Q. Zhao, “Clinnical study on treatment of essential hypertension
Ac ce pt e
13
M
10
with moxibustion,” Liaoning Zhong Yi, vol. 35, no. 7, pp. 1085-1086, 2008.
15
[61] K. Zhang, J. Zheng, and N. Wang, “Herbs-partitioned moxibustion on umbilicus for
16
hypertension with liver yang hyperactivity syndrome,” Zhejiang Zhong Yi Za Zhi, vol. 42, no.
17
7, pp. 417, 2007.
18
[62] K. Zhang and J. Zheng, “Herbs-partitioned moxibustion on umbilicus combined with
19
amlodipine besylate tablets for 30 cases of hypertension with liver yang hyperactivity
20
syndrome,” Shanxi Zhong Yi, vol. 32, no. 2, pp. 205-206, 2011.
21
[63] B. Y. Huang, J. M. Zhu, W. G. Huang, and X. Z. Lin, “Clinical observation of the treatment
22
of elderly patients with hypertension by moxibustion,” Xin Zhong Yi, vol. 43, no. 12, pp. 21
Page 21 of 27
1
87-88, 2011. [64] J. E. Park, S. S. Lee, M. S. Lee, S. M. Choi, and E. Ernst, “Adverse events of moxibustion: a
3
systematic review,” Complementary Therapies in Medicine, vol. 18, pp. 215-223, 2010.
4
[65] X. J. Xiong, X. C. Yang, B. Feng, W. Liu, L. Duan, A. Gao, H. X. Li, J. Z. Ma, X. L. Du, N.
5
Li, P. Q. Wang, K. L. Su, F. Y. Chu, G. H. Zhang, X. K. Li, and J. Wang, “Zhen gan xi feng
6
decoction, a traditional Chinese herbal formula, for the treatment of essential hypertension: a
7
systematic review of randomized controlled trials,” Evidence-Based Complementary and
8
Alternative Medicine, vol. 2013, Article ID 982380, 9 pages, 2013.
us
cr
ip t
2
[66] J. Wang, B. Feng, and X. J. Xiong, “Chinese herbal medicine for the treatment of
10
obesity-related hypertension,” Evidence-Based Complementary and Alternative Medicine, vol.
11
2013, Article ID 757540, 11 pages, 2013.
M
an
9
[67] D. Moher, S. Hopewell, K. F. Schulz, V. Montori, P. C. Gøtzsche, P. J. Devereaux, D.
13
Elbourne, M. Egger, and D. G. Altman, “CONSORT 2010 Explanation and Elaboration:
15 16 17 18
Ac ce pt e
14
d
12
updated guidelines for reporting parallel group randomised trial,” International Journal of Surgery, vol. 10, pp. 28-55, 2012.
19 20 21 22 22
Page 22 of 27
1
Figure Legend
2
Figure 1: PRISMA 2009 Flow Diagram.
Ac ce pt e
d
M
an
us
cr
ip t
3
23
Page 23 of 27
Conflicts of Interests All authors declare that they have no conflicts of interests.
d
M
an
us
cr
ip t
Acknowledgment The current work was partially supported by the National Basic Research Program of China (973 Program, No. 2003CB517103) and the National Natural Science Foundation Project of China (No. 90209011). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Ac ce pt e
1 2 3 4 5 6 7 8 9
24
Page 24 of 27
1
Table1: Characteristics and methodological quality of included studies. Control
Course
Outcome measure
66
1999 WHO -ISH GMH
moxibustion + control
antihypertensive drugs (no detailed information)
10 days
BP
60
1999 WHO -ISH GMH
moxibustion
10 days
BP
51
1999 WHO -ISH GMH
moxibustion
maleate enalapril (10 mg qd) amlodipine besylate (5-10 mg qd)
30 days
BP
60
1999 WHO -ISH GMH
moxibustion + control
amlodipine besylate (5-10 mg qd)
30 days
BP
120
CGMH-2004
moxibustion + control
21 days
BP
ip t
hang et 2011 9] n et al. 008 [60] hang et 2007 1] hang and heng 011 [62] uang et 2011 3]
Intervention
cr
Diagnosis standard
us
Sample
Beijing hypotensive No.0 (1# qd)
an
udy ID
2 3 4 5
M
Table 2: Quality assessment of included randomized controlled trials. Random sequence generation
Allocation concealment
Blinding of participants and personnel
Blinding of outcome assessment
Incomplete outcome data
Selective reporting
Other sources of bias
Risk o bias
hang et al. 2011 [59] n et al. 2008 [60] hang et al. 2007 [61] hang and Zheng 11 [62] uang et al. 2011 [63]
drawing Unclear Unclear Unclear
Unclear Unclear Unclear Unclear
Unclear Unclear Unclear Unclear
Unclear Unclear Unclear Unclear
Yes Yes Yes Yes
No No No No
Unclear Unclear Unclear Unclear
Unclea High High High
Unclear
Unclear
Unclear
Unclear
Yes
No
Unclear
High
Ac ce pt e
6 7 8 9
d
Included trials
Table 3: Analyses of blood pressure.
Trials
Intervention (n/N)
Control (n/N)
RR [95% CI]
P Value
moxibustion versus antihypertensive drugs moxibustion versus maleate enalapril moxibustion versus amlodipine besylate
1 1
25/30 21/30
23/30 17/24
1.52 [0.42, 5.47] 0.96 [0.30, 3.12]
0.52 0.95
Meta-Analysis
2
46/60
40/54
1.19 [0.50, 2.81]
0.70
1
28/30
24/30
3.50 [0.65, 18.98]
0.15
moxibustion plus antihypertensive drugs versus antihypertensive drugs moxibustion plus amlodipine besylate versus amlodipine besylate
25
Page 25 of 27
moxibustion plus Beijing hypotensive No.0 versus Beijing hypotensive No.0
1
58/60
54/60
3.22 [0.62, 16.66]
0.16
Meta-Analysis
2
86/90
78/90
3.35 [1.03, 10.89]
0.04
1 2 3 4
Table 4: Analyses of systolic blood pressure. MD [95% CI] drugs
moxibustion plus antihypertensive versus antihypertensive drugs
drugs
Meta-Analysis
-9.57 [-10.80, -8.34]
1
-9.57 [-10.80, -8.34]
an
drugs
moxibustion plus antihypertensive versus antihypertensive drugs
drugs
MD [95% CI]
P Value
1
-4.08 [-4.60, -3.56]
< 0.00001
1
-4.08 [-4.60, -3.56]
< 0.00001
Ac ce pt e
d
M
moxibustion plus antihypertensive versus antihypertensive drugs
Meta-Analysis
13
< 0.00001
Table 5: Analyses of diastolic blood pressure. Trials
9 10 11 12
< 0.00001
us
5 6 7 8
1
cr
moxibustion plus antihypertensive versus antihypertensive drugs
P Value
ip t
Trials
26
Page 26 of 27
Ac ce p
te
d
M
an
us
cr
ip t
Figure
Page 27 of 27