Chin J Integr Med •1•

C
Available online at link.springer.com/journal/11655
hinese Journal of Integrative Medicine Journal homepage: www.cjim.cn/zxyjhen/zxyjhen/ch/index.aspx
E-mail: cjim_en@cjim.cn

Evidence-Based Integrative Medicine

Conventional Acupuncture for Cardiac Arrhythmia:
A Systematic Review of Randomized Controlled Trials
LIU Jing1,2, LI Si-nai3, LIU Lu1,2, ZHOU Kun4, LI Yan1,2, CUI Xiao-yun1,2, WAN Jie5,
LU Jin-jin1,2, HUANG Yan-chao1,2, WANG Xu-sheng5, and LIN Qian1,2

ABSTRACT Objective
Objective:: To exam the effect and safety of conventional acupuncture (CA) on cardiac arrhythmia.
Methods:: Nine medical databases were searched until February 2016 for randomized controlled trials.
Methods
Heterogeneity was measured by Cochran Q test. Meta-analysis was conducted if I2 was less than 85% and the
characteristics of included trials were similar. Results
Results:: Nine qualified studies involving 638 patients were included.
Only 1 study had definitely low risk of bias, while 7 trials were rated as unclear and 1 as high. Meta-analysis of CA
alone did not have a significant benefit on response rate compared to amiodarone in patients with atrial fibrillation
(Af) and atrial flutter (AF) [relative risk (RR): 1.09; 95% confidence interval (CI): 0.79–1.49; P =0.61; I2=61%,
P =0.11]. However, 1 study with higher methodological quality detected a lower recurrence rate of Af in CA alone
as compared with sham acupuncture plus no treatment, and benefits on ventricular rate and time of conversion to
normal sinus rhythm were found in CA alone group by 1 study, as well as the response rate in CA plus deslanoside
group by another study. Meta-analysis of CA plus anti-arrhythmia drug (AAD) was associated with a significant
benefit on the response rate when compared with AAD alone in ventricular premature beat (VPB) patients (RR,
1.19, 95% CI: 1.05–1.34; P =0.005; I2=13%, P =0.32), and an improvement in quality-of-life score (QOLS) of VPB
also showed in 1 individual study. Besides, a lower heart rate was detected in the CA alone group by 1 individual
study when compared with no treatment in sinus tachycardia patients (MD –21.84 [–27.21, –16.47]) and lower
adverse events of CA alone were reported than amiodarone. Conclusions
Conclusions:: CA may be a useful and safe alternative
or additive approach to AADs for cardiac arrhythmia, especially in VPB and Af patients, which mainly based on a
pooled estimate and result from 1 study with higher methodological quality. However, we could not reach a robust
conclusion due to low quality of overall evidence.
KEYWORDS acupuncture, cardiac arrhythmia, systematic review

Cardiac arrhythmia, is a group of conditions
in which the heartbeat is irregular, too fast, or too
slow. At present, premature beats, supraventricular
tachycardia, ventricular arrhythmia, conduction block
and bradyarrhythmia are main types of arrhythmia.
Premature beats mainly include atrial premature beats
and ventricular premature beat (VPB). Supraventricular
tachycardias include atrial fibrillation (Af), atrial flutter
(AF), and paroxysmal supraventricular tachycardia
(PSVT). Ventricular arrhythmias include ventricular
fibrillation and ventricular tachycardia.(1,2) The current
standard therapies for cardiac arrhythmia are anti-
arrhythmia drugs (AADs), cardioversion, radio frequency
ablation or implantable electronic devices.(3-5) Although
AADs are more often used and can effectively alleviate
symptoms of arrhythmia, concerns raised about their
proarrhythmic action and common side effects (e.g.,
dry mouth, dizziness, vision problems, renal damage).
Consecutive researches have confirmed proarrhythmic
action and poor prognosis of guideline-directed AADs,
including flecainide, amiodarone, dronedarone,
ivabradine and so on. (6-12) In addition, selection of
other approaches depends heavily on the character of
arrhythmia and underlying disease, and their use are
limited by strict indications and high cost.(13,14)
©The Chinese Journal of Integrated Traditional and Western
Medicine Press and Springer-Verlag Berlin Heidelberg 2017
Supported by the National Natural Science Foundation of China
(No. 81173176)
1. Beijing University of Chinese Medicine, Beijing (100078),
China; 2. Department of Cardiology, Dongfang Hospital, Beijing
University of Chinese Medicine, Beijing (100078), China; 3.
Beijing Institute of Traditional Chinese Medicine, Beijing Hospital
of Traditional Chinese Medicine, Capital Medical University,
Beijing (100010), China; 4. Scientific Research Division, Dongfang
Hospital, Beijing University of Chinese Medicine, Beijing (100078),
China; 5. Intensive Care Unit, Dongfang Hospital, Beijing
University of Chinese Medicine, Beijing (100078), China
Correspondence to: Dr. LIN Qian, Tel: 86-10-67689611, E-mail:
13910565673@126.com
DOI: 10.1007/s11655-017-2753-9
•2•
The limitations associated with Western medicine
approaches led to an increasing interest in developing
alternative and complementary interventions. As an
old approach of Chinese medicine (CM), acupuncture
has a long history in treating palpitation which is
the most typical symptom of arrhythmia. In animal
models, acupuncture has been proved to be effective
in attenuating and suppressing arrhythmias mainly
through regulating the nervous and endocrine
systems. (15) Whether this effect can be translated
into favorable clinical outcomes was assessed in
randomized clinical trials (RCTs) that comparing
acupuncture to AADs, sham acupuncture or no
treatment. Various characteristics of these trials yielded
different results, which demanding further exploration.
Previous reviews focused on this issue published
in 2008 and 2011.(16,17) Only the latter was systematic
review (SR), but explored effect of all kinds of
acupuncture and included studies of small sample
size and inconsistent baseline. Besides, through
pre-searching, more studies have examined this
treatment among the following 4 years. In this SR we
applied more rigorous inclusion and exclusion criteria,
and aimed to explore whether acupuncture rooted in
traditional meridian theory (the theory of 12 regular
meridians and 8 extra meridians), which was named
as conventional acupuncture (CA), was effective
for cardiac arrhythmia. Because CA not only has a
wider application in clinical practice, but also is more
available and easier to be accepted due to its unified
theory.
METHODS
This SR were reported according to the
Preferred Reporting Items for Systematic Reviews
and Meta-Analyses (PRISMA) Statement(18) and the
Cochrane Handbook. (19) Protocol was registered
at PROSPERO and the registration number is
CRD42016045274 (available at: http://www.crd.york.
ac.uk/PROSPERO_REBRANDING/display_record.
asp?ID=CRD42016045274).
Search Strategy
A comprehensive search of 9 medical databases,
including MEDLINE (PubMed and OVID), EMBASE
(OVID), the Allied and Alternative Medicine Database
(OVID), CINAHL (EBSCO), the Cochrane Library,
China National Knowledge Infrastructure (CNKI),
Chinese Scientific Journals Database (VIP), Wanfang
Chin J Integr Med
Database and Chinese Biomedical Database (CBM)
were conducted until February 2016 without language
restriction. We searched individually or combined
Mesh terms with abstract, title, or key words relating
to the intervention of interest (acupuncture, acupoint,
needle, moxibustion, meridian, or acupressure),
terms relating to the patients of interest (cardiac
arrhythmias, cardiac channelopathy, or heart muscle
conduction disturbance), and to the study design
(randomized, randomly, and clinical trial). We also
searched relevant references of obtained studies and
review articles by hand to identify eligible resources.
The above terms in Chinese were searched in
Chinese databases.
Eligibility Criteria
Three reviewers (Liu J, Liu L and Huang
YC) identified studies for eligibility independently.
Any disagreement was resolved by consensus or
consultation with a third reviewer (Li SN). Only
a study satisfying all the following criteria could
be included: (1) patients diagnosed as any type
of cardiac arrhythmia, which was confirmed by
electrocardiogram (ECG) or ambulatory rhythm
monitoring (e.g., telemetry, Holter monitor, event
recorder), with no limitations on gender, age, course
and co-morbidity, but baseline characteristics
of each study should be consistent. Malignant
arrhythmia accompanied with hemodynamic
instability or required immediate defibrillation, such
as ventricular tachycardia or ventricular fibrillation,
were excluded. The diagnostic criteria for each kind
of arrhythmia was detailed in Appendix 1. (2) The
form of acupuncture should be rooted in traditional
meridian theory, which auricular acupuncture, scalp
acupuncture (based on the function of cerebral
cortex), transcutaneous electrical nerve stimulation,
laser acupuncture and wrist-ankle acupuncture
were excluded. The stimulating modalities can
be filiform acupuncture, electro-acupuncture,
fire needle acupuncture, plum-blossom needle
acupuncture, acupoint catgut implantation, acupoint
injection, acupoint drug application, acupressure,
or acupoint moxibustion. (3) Trials comparing CA
alone or CA plus AAD to AAD, sham acupuncture or
no treatment that allows evaluation of the add-on or
net effectiveness of CA. Other co-intervention was
allowed if this was applied in both arms. A wide range
of intervention time from 5 min to 3 months was
eligible. (4) Our primary outcomes were mortality,
Chin J Integr Med
recurrence rate, or readmission rate. Clinical or
surrogate outcomes were also eligible, including
response rate, heart rate (HR), ventricular rate
(VR), time of conversion to normal sinus rhythm
(NSR) and quality-of-life score (QOLS). Only no
arrhythmia recurrence, or a percentage of reduction
of arrhythmia attacks higher than 50%, or HR or
VR less than 90 beats per minute (bpm), or grade
reduction of VPB or conduction block more than 1 was
considered as response. Besides, adverse events
were considered as a primary safety outcome. (5) All
peer-reviewed, full-reported parallel randomized or
quasi-RCTs irrespective of blinding were qualified, but
small sample studies (less than 30 cases), duplicate
reports and pilot studies were excluded. In addition,
the first phase data of randomized cross-over trials
were also included for analysis.
Data Extraction
Two reviewers (Liu L and Zhou K) extracted data
independently using extraction form. Disagreement
was resolved by census or consultation with the third
reviewer (Li SN). The following items were extracted:
study name, year of publication, study setting, sources
of founding, sample size, details of trial design (i.e.,
randomization, allocation concealment, blinding),
eligibility criteria, general characteristics of patients
(i.e., gender, age, type of arrhythmia, arrhythmia
course and severity, co-morbidities), details of
intervention and control therapy, details of effective
outcomes and safety outcomes, and other information
that may help detect bias (i.e., register No., data for
analysis, termination time).
Quality Assessment
Two reviewers (Li Y and Cui XY) independently
assessed the methodological quality of the included
studies using the Cochrane Collaboration's tool,(20)
which is a domain-based evaluation tool to generate
a 'risk of bias' table for each study. Any disagreement
was resolved by consensus or consultation with a
third reviewer (Wan J). The domains for assessment
were sequence generation (selection bias), allocation
concealment (selection bias), blinding of participants
and personnel (performance bias), blinding of
outcome assessment (detection bias), incomplete
outcome data (attrition bias), selective outcome
reporting (reporting bias), and other potential sources
of bias (e.g., early termination, carry-over in cross-
over trials, contamination, conflict of interest).
•3•
Data Synthesis and Analysis
Data synthesis and analysis were performed
with RevMan software 5.3. (19) Dichotomous data
were measured as relative risk (RR) and continuous
data as mean difference (MD) or standardized mean
difference (SMD), both with corresponding 95%
confidence interval (CI). Heterogeneity across trials
was measured by Cochran Q test and presented as
I2 statistics. Only those trials with I2 less than 85%
were used for meta-analysis and the characteristics
of included trials were similar (i.e., same type of
arrhythmia, same comparison, and same outcome). A
fixed effect model was used if I2 was less than 25%,
otherwise a random effect model was applied under
the circumstances that heterogeneity was readily
explainable. Furthermore, subgroup analysis defined
by age, gender, type of CA, severity of condition, or
intervention period, and sensitivity analysis stratified
by quality of included trials, and funnel plot were
performed to detect heterogeneity and publication
bias if sufficient sources were available. A 2-tailed
P value less than 0.05 was considered as statistical
significance. Approaches to overcome a unit-of-
analysis error for a study that could contribute multiple,
correlated comparisons lied in combining groups to
create a single pair-wise comparison.(21) For example,
patients of two or more CA relevant experimental
intervention groups in one study would be integrated
into a single experimental group, as well as sham
acupuncture and no treatment into a single control
group.(22)
RESULTS
Description of Included Studies
The search strategy identified 14,530 studies,
of which only 9 qualified studies(23-31) were included,
involving 638 patients with cardiac arrhythmia (Figure
1). A total of 320 patients underwent CA alone or CA
plus AAD and 318 patients underwent AAD or sham
acupuncture or no treatment.
The included studies were published between
1999 and 2012, with 4 studies (44.4%) published
since 2011. Eight studies were conducted in China
mainland(23-30) and 1 in Italy.(31) There were 2 three-
arm trials(24,31) and 1 quasi-RCT,(27) while the remaining
trials had a parallel two-arm completely randomized
controlled design. The types of cardiac arrhythmia
varied: VPB (n =3),(23,27,28) Af and/or AF (n =4),(26,29-31) sinus
tachycardia (ST, n =1)(24) and PSVT (n =1).(25) Three
•4• Chin J Integr Med

• 10,854 records identified through searching 6 English databases rate related to long-term prognosis (31) and only 3
• 3,658 records identified through searching 4 Chinese databases
trials fully reported adverse events. (26,30,31) Detailed
• 18 additional records identified through hand searching
characteristics of included studies are shown in
2,861 records removed
for duplication Appendixes 2 and 3, Tables 1 and 2.
11,669 records screened
Methodological Quality Assessment
11,588 records
screened out Almost all included trials describing a
81 full-text articles 72 excluded:
randomization process were judged as low risk of
assessed for eligibility -Protocol (n =2) bias, but 1 study mentioning "quasi-randomization"
-Review (n =3)
-Non-RCT (n =2) was considered as high risk of bias.(27) All or majority
-Non peer reviewed (n =2) of the included trials had unclear risk of bias in the
-Duplicated reports (n =7)
9 studies included in -Failed to meet inclusion domains of allocation concealment (n =9), blinding
final synthesis criteria (n =56)
of outcome assessment (n =8), incomplete outcome
Figure 1. Study Flow Diagram data (n =8), and selective outcome reporting (n =9),
because there were insufficient information to
main acupuncture modalities were used, including confirm judgment of "low" or "high" risk of bias. Due
filiform needle (n =7), acupoints injection (n =1) and to difficulties in applying blinding for the participants
acupoints catgut implantation (n =1), comparing with and personnel when comparing acupuncture with
AADs (n =7), sham acupuncture (n =1) or no treatment Western medicine or no treatment, we judged 8 trials
(n =2). AADs chosen for comparison were mexiletine, failed to report this domain as high risk of bias. Only
propafenone and amiodarone which were classified 1 study had definitely low risk of bias in 3 domains
asⅠb,Ⅰc, and Ⅲ AAD respectively. In addition, 1 related to blinding and completeness of outcome
study used deslanoside as comparison. The treatment data. (31) In conclusion, the overall methodological
period varied from 20 min to 60 days. The most quality of 8 trials (23-26,28-31) were rated as unclear
frequently reported outcome was response rate because most domains of them were at low or unclear
(n =8). Other involving outcomes were reduction of risk of bias, while that of 1 trial(27) as high because 2
HR, mean VR, QOLS and time of conversion to NSR. domains were classified as high risk of bias. Details
All the outcomes were measured by ECG or 24-h are shown in Figure 2. Besides, we did not draw a
holter. However, only 1 study reported recurrence funnel plot or conduct any publication bias-related

Table 1. Response Rate of CA alone or CA plus AAD on Cardiac Arrhythmia in Individual Studies
EG CG
Study Intervention CAR RR [95% CI]
EE Total EE Total
Dong, et al 2006(25) CA vs . Propafenone PSVT 25 32 25 28 0.88 [0.70, 1.09]
(29)
Han, et al 2012 CA +deslanoside vs . Deslanoside Af and AF 49 62 30 52 1.37 [1.05, 1.79]△
(31)
Lomuscio, et al 2011 CA vs . Sham acupuncture + no treatment Af (immediately p-tr.) 16 17 25 37 1.39 [1.08, 1.79]△
Af (3 months p-tr.) 14 17 19 37 1.60 [1.09, 2.35]△
Af (6 months p-tr.) 12 17 18 37 1.45 [0.92, 2.28]△
Af (9 months p-tr.) 11 17 15 37 1.60 [0.94, 2.70]△
Notes: p-tr.: post-treatment; EE: effective events; filiform needle; △favoring EG

Table 2. Other Outcomes of CA alone or CA plus AAD on Cardiac Arrhythmia in Individual Studies
EG CG
Study Intervention Outcome (U)-CAR MD [95% CI]
Case x–±s Case x–±s
Li, et al 2003(24) CA vs . No treatment HR (bpm)-ST 30 90.0±10.6 30 111.9±10.6 –21.84 [–27.21, –16.47]△
(26)
Xu, et al 2007 CA vs . Amiodarone VR (bpm)-Af and AF 40 64.7±12.6 40 85.2±21.7 20.50 [–28.28, –12.72]△
Chen, et al 2012(30) CA vs . Amiodarone VR (bpm)-Af 30 114.5±13.4 30 111.2±11.3 3.21 [–3.04, 9.46]
(26)
Xu, et al 2007 CA vs . Amiodarone TCN (min)-Af and AF 40 39.6±13.7 40 50.1±14.8 –10.50 [–16.75, –4.25]△
(28)
Wang, et al 2012 CA + mexiletine vs . Mexiletine QOLS-VPB 57 75.0±15.7 53 62.5±14.9 12.53 [6.81, 18.25]△

Notes: TCN: time of conversion to NSR ; filiform needle; acupoints catgut implantation; acupoints Injection; △ favoring EG
Chin J Integr Med •5•

test due to insufficient number of studies and the high response rate than intravenous deslanoside alone
heterogeneity between studies, whereas we were (RR, 1.37; 95% CI: 1.05–1.79; Table 1). Another
unable to make a definite conclusion on the existence individual study(31) with higher methodological quality,
of publication bias because not all included studies favored the effectiveness of CA alone in reducing the
reported positive results. recurrence of Af in patients undergone an electrical
conversion as compared with sham acupuncture plus

Blinding of perticipants and personnal (parformance bias)

no treatment (RR, 1.39; 95% CI: 1.08–1.79); this
favorable effect continued till 3 months after treatment

Blinding of outcome assassment (detection bias)

Random sequence generation (selection bias)

(RR, 1.60; 95% CI: 1.09–2.35), but failed at 6 and

9 months after treatment (RR: 1.45, 95% CI: 0.92,
Incomplete outcome data (attrition bias)
Allocation concealment (selection bias)

2.28; RR: 1.60, 95% CI: 0.94, 2.70, respectively,

Selective reporting (reporting bias) Table 1). Moreover, the 2 studies included in
the meta-analysis also compared VR between
groups,(26,30) and only the former showed a significant
Low risk of bias
Unciear risk of bias reduction of VR in CA alone group (MD: –20.50, 95%
Other bias

High risk of bias

CI: –28.28, 12.72;(26) MD: 3.21, 95% CI: –3.04, 9.46(30))
however a meta-analysis could not be performed
Chen 2012 due to a high heterogeneity (I2=95%, P <0.0001). In
Dong 2006
addition, CA alone also showed a shorter time of
Han 2012
conversion to NSR in Af patients in 1 study,(26) when
Li 2003
comparing with intravenous amiodarone (MD: –10.50,
Liu 1999
95% CI: –16.75, –4.25; Table 2).
Lomuscio 2011

Wang 2012

Xu 2007 Effects of CA on VPB

Zhong 2008 Three studies (23,27,28) provided evidence of
measuring add-on effect of CA plus AAD on response
Figure 2. Summary of Risk of Bias in
Included Studies
rate of VPB comparing with AAD alone (i.e., oral
propafenone, oral propafenone and metoprolol, oral
Effects of CA on Af and AF mexiletine, respectively). In the meta-analysis of
Four studies assessed the effects of CA on Af these 3 studies, CA plus AAD was associated with a
and AF.(26,29-31) Meta-analysis of 2 studies(26,30) showed significant benefit on the response rate (RR, 1.19, 95%
that, compared with oral or intravenous amiodarone, CI: 1.05–1.34; P =0.005; I2=13%, P =0.32, Figure 4).
CA alone had no better effect on response rate (RR, Then a sensitivity analysis was conducted within these
1.09; 95% CI: 0.79–1.49; P =0.61; I2=61%, P =0.11) studies by excluding the quasi-randomized study,(27)
(Figure 3). As the heterogeneity might come from a significant benefit still existed in the CA plus AAD
the difference in severity of condition, acupuncture group (RR, 1.23, 95% CI: 1.07–1.41; P =0.003; I2=0%,
modality, criteria of outcome evaluation or length of P =0.50). In addition, 1 individual study(28) showed a
treatment, a random-effect model was used here. significant improvement on the QOLS measured with
However, 1 individual study(29) showed that CA plus SF-36 Questionnaire in the CA plus oral mexiletine
intravenous deslanoside had better add-on effect on group (MD, 12.53, 95% CI: 6.81–18.25, Table 2).

CA Amiodarone RR RR
Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI
Xu 2007 34 40 27 40 53.9% 1.25 [0.98, 1.62]
Chen 2012 21 30 23 30 46.1% 0.91 [0.67, 1.24]
Total (95% CI) 70 70 100.0% 1.09 [0.79, 1.49]
Total events 66 50
Heterogeneity: Tau2=0.03, Chi2=2.53, df=1 (P =0.11); I2=61%
0.01 0.1 1 10 100
Test for overall effect Z =0.51 (P =0.61)
Favours [Amiodarone] Favours [CA]

Figure 3. Meta-Analysis of Response Rate of Conventional Acupuncture

Alone on Af and AF as Compared with Amiodarone
•6•
CA+AAD AAD
Study or Subgroup Events Total Events
Liu 1999 30 32 25
Zhong 2008 18 20 15
Wang 2012 52 57 38
Total (95% CI) 109
Total events 100 78
Heterogeneity: Chi2=2.29, df=2 (P =0.32); I2=13%
Test for overall effect Z =2.82 (P =0.005)
Figure 4. Meta-Analysis of Response Rate of CA plus AADs on VPB Compared with AADs Alone
Effects of CA on Other Cardiac Arrhythmias
(24)
One study assessed the net effect of CA
alone on ST as compared with no treatment. After
one session of 30-min treatment, a lower HR was
detected in the CA alone group (MD: –21.84; 95%
CI: –27.21, –16.47; Table 2). Although 1 study (25)
explored the effect of CA alone on PSVT as compared
with intravenous propafenone, no significant benefit
was discovered on response rate after one session
of 20-min treatment in the CA alone group (RR, 0.88;
95% CI: 0.70–1.09; Table 1).
Adverse Events
Only 3 studies (26,30,31) provided information
about adverse events. Patients suffered more
adverse events in AAD alone group than CA alone
group. Adverse events related to oral or intravenous
amiodarone, including anorexia, sinus tachycardia,
Ⅰ atrial-ventricular block, hypotension (systolic blood
pressure <90 mm Hg), and vomiting, were reported
in 2 studies.(26,30) CA alone did not cause bleeding,
hematoma, infection, pain or vaso-vagal reactions in
1 study,(31) but red swelling and itchy skin caused by
acupoint catgut implantation were reported in another
study.(30)
DISCUSSION
In this SR, we included 9 studies exploring the net
or add-on effectiveness of CA on cardiac arrhythmia.
In Af and AF patients, a meta-analysis of 2 studies
failed to find a significant difference between CA and
amiodarone, although one of those studies showed a
lower VR and a shorter time of conversion to NSR in
CA alone group. Besides, 1 individual study showed
a higher response rate in CA plus deslanoside as
compared to deslanoside alone in Af patients; another
study with higher methodological quality, which included
Af patients undergone an electrical conversion, showed
a lower recurrence rate that continued till 3 months
after treatment in CA alone group, when compared with
Chin J Integr Med
RR RR
Total Weight M-H, Fixed, 95% CI M-H, Fixed, 95% CI
31 31.4% 1.16 [0.96, 1.41]
17 20.0% 1.02 [0.81, 1.28]
53 48.8% 1.27 [1.06, 1.53]
101 100.0% 1.19 [1.05, 1.34]
0.01 0.1 1 10 100
Favours [Amiodarone] Favours [CA]
sham acupuncture plus no treatment. In VBP patients,
a meta-analysis of 3 studies showed a significantly
higher response rate in CA plus AAD compared to
AAD alone; this positive result was corroborated in
a sensitivity analysis, where 1 quasi-randomized
study was excluded. A favorable effectiveness of
alleviating QOLS for VPB was also detected in CA
plus mexiletine. Despite the fact that only 3 studies
detailed adverse events, lower adverse events of CA
alone were reported than amiodarone. Furthermore, in
ST patients, 1 individual study showed that CA alone
was associated with a lower HR as compared with no
treatment, whereas in PSVT patients CA alone failed
to show significant difference in response rate as
compared with propafenone.
Given the limitations identified in this SR,
cautious conclusions should be drawn about these
positive findings. First of all, although research
strategy conducted sensitively enough, 45 trials
failing to meet the inclusion criteria were excluded,
including studies applying CA on both arms, which
brought difficulty to draw a whole picture for effect
of CA on arrhythmia. Secondly, the included studies
failed to provide sufficient information for assessing
the methodological quality. To be specific, half of the
included studies did not describe the way to produce
random sequences, and not even a study referred
to allocation concealment. Serious doubt was raised
about proper conduction of randomization. In addition,
although it is difficult to perform blinding of participants
and personnel in acupuncture, we could not find a
good reason to explain why almost all included studies
failed to claim blinding of outcome assessment.
Moreover, since no registered protocol was retrieved,
assessment of incomplete outcome data, selective
reporting and other bias became unavailable. Besides,
due to insufficient studies for each outcome, we were
incapable of conducting a funnel plot or related test
to detect publication bias. Thirdly, potential ethnic
Chin J Integr Med
heterogeneity may exist because included populations
were either from China mainland or Italy. Another
important concern is that almost all studies observed
short-term surrogate outcomes (up to 60 days) other
than prognosis-related endpoints, in these cases
potential adverse events, or long-term low or no benefit
may exist, which will greatly influence the interpretation
of results. For example, although a lower recurrence
rate of CA alone was founded immediately and 3
months after treatment in one included study, this
benefit faded away at 6 and 9 months after treatment.(31)
However, although limitations restricted, an
effective trend of CA alone or CA plus AAD can
be said in Af and VPB patients. In this SR, the
stimulated acupoints and their distribution proportions
were Neiguan (PC 6) 25%, Xinshu (BL15), 14.3%,
Shenmen (HT 7) 10.7%, Zusanli (ST 36) 10.7%,
Juque (CV 14) 7.1%, Xuehai (SP10) 7.1%, Ximen
(PC 4) 3.6%, Jueyinshu (BL 14) 3.6%,Danzhong
(CV 17) 3.6%, Qihai (CV 6) 3.6%, Zhongwan (CV
12) 3.6% and Sanyinjiao (SP 6) 3.6%, respectively.
The meridians, where frequently used acupoints
were located, were Pericardium, Governor, Xin
(Heart), Wei (Stomach), Pi (Spleen), and Conception
Meridians. Based on CM doctrine, (32,33) a close
relationship exists within these meridians, no matter
in position or function. Treating arrhythmia with CA is
to restore yin-yang balance of heart based on close
interaction between meridians, their belonged viscera
and specificity of acupoints.(34) On the other hand, rat
model experiments had proven CA effectiveness,
such as, in protecting the myocardial tissue from
acute myocardial infarction by increasing gap junction
protein 43, nitric oxide, and endothelin of ischemic
myocardium, (35,36) reducing the left ventricular
hypertrophy by inhibiting tumor growth factor (TGF)-
β1-TAK1-p38MAPK signaling pathway, (37) and
improving the coronary artery flow in coronary artery
disease patients by down-regulating thromboxane
B2 and 6-ketone-prostaglandin.(38) Moreover, many
animal studies have certified the effectiveness of
CA on electrophysiological mechanism underlying
the arrhythmia, which mainly through decreasing
early after depolarization, stabilizing ventricular
myocytes transmembrane potential, (39) inhibiting
calcium homeostasis related proteins cyclic
adenosine monophosphate and protein kinase A,(40)
or decreasing the emergence of Ca2+ oscillation.(41) As
above illustrated, the beneficial trend of CA on cardiac
•7•
arrhythmia may come from its effects on upstream
diseases and electrophysiological mechanism.
Hopefully, some points could be paid attention
to in subsequent studies as follows. Firstly, the
clinical trial should be prospectively registered at
recognized international or domestic registry sites,
so that reviewers can determine whether risk bias of
incomplete outcome data and selective reporting exist,
as well as publication bias. Secondly, information
about random sequence generation, allocation
concealment, or application of blinding should be
reported as detailed as possible according to the
PRISMA Statement, which will allow the reviewers
an all-around assessment of methodological quality.
Thirdly, except for the short-term and surrogate
outcomes, researchers should pay more attention to
clinical prognosis-related endpoints in order to avoid
arbitrary conclusion. As the essential purpose of CM
is to modulate the overall status of human body, the
main benefit of CM may mostly lie in the improvement
of patient's external symptoms and signs rather than
laboratory biological indices. Therefore, the importance
of application of such kind of outcomes (e.g., quality of
life and activities of daily living) should be emphasized
in future acupuncture-related studies.(42) Finally, larger
sample size that is greater than or equal to optimal
information size(43) should be calculated in order to
produce more precise results.
In summary, this SR suggested that CA may be a
useful and safer alternative or additive approach to AADs
especially for VPB and Af patients, which mainly based
on a pooled estimate and result of one study with higher
methodological quality. However, we should be cautious
with the interpretation and application of the results in
clinical practice due to low quality of overall evidence.
As acupuncture world-wide use, the benefit trend of CA
alone or CA plus AAD on cardiac arrhythmia showed
in this SR may be meaningful in finding a breakthrough
to reduce AADs dependence and side effects. Well-
designed studies of high methodological quality are the
cornerstones to reach this goal.
Conflict of Interests
The authors declare that there is no conflict of interest
regarding the publication of this paper.
Author Contributions
Lin Q had full access to all of the data in this SR and was
•8•
responsible for data integrity and accuracy of data analysis. Liu J,
Li SN and Wang XS designed this study. Liu J, Li SN, Liu L, Zhou
K and Huang YC settled eligibility criteria, performed literature
search, conducted data extraction and carried out statistical
analysis. Liu J, Li SN, Liu L, Zhou K drafted the manuscript. Li
Y, Cui XY, Wan J and Lu JJ contributed to quality assessment,
interpretation of results, and critical revision of the manuscript.
Electronic Supplementary Material: Supplementary material
(Appendixes 1–3) is available in the online version of this article
at http://dx.doi.org/10.1007/s11655-017-2753-9.
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(Received October 9, 2016)
Edited by YUAN Lin