acupuncture therapy for angina pectoris: a systematic … · if they used other antianginal drugs,...

JTCM |www. journaltcm. com December 15, 2012 |volume 32 | Issue 4 |

Online Submissions: http://www.journaltcm.com J Tradit Chin Med 2012 December 15; 32(4): [email protected] ISSN 0255-2922

© 2012 JTCM. All rights reserved.

EVIDENCE-BASED STUDY

Acupuncture therapy for angina pectoris: a systematic review

Ji Chen, Yulan Ren, Yong Tang, Zhengjie Li, Fanrong Liangaa

Ji Chen, Yulan Ren, Yong Tang, Zhengjie Li, Fanrong Li-ang, Chengdu University of Traditional Chinese Medicine,Chengdu 610075, Sichuan, ChinaSupported by the National Basic Research Program of Chi-na (973 Program) for "Basic Research on Acupoint SpecificityAlong Medians and its Crucial Influential Factors" (No.2012CB518501)Correspondence to: Prof. Fanrong Liang, Chengdu Univer-sity of Traditional Chinese Medicine, Chengdu 610075, Sich-uan, China. [email protected]: +86-28-61800006Accepted: June 11, 2012

AbstractOBJECTIVE: To assess the effectiveness and safetyof acupuncture therapy for angina pectoris.

METHODS: Randomized controlled trials (RCTs)concerned with acupuncture treatment of anginapectoris were identified by searching AcademicSource Premier, MEDLINE, Science Citation IndexExpanded, and three Chinese databases (China biol-ogy medicine database, China national knowledgeinfrastructure, and VIP database for Chinese techni-cal periodicals). The valid data were extracted in ac-cordance with our inclusion and exclusion criteria.The main outcomes of the included studies weresynthesized using Revman 5.1.

RESULTS: Twenty-one articles on 16 individualstudies were included and evaluated as havinghigh or moderate risk of bias according to the stan-dards of the Cochrane Collaboration. Meta-analysisindicated that acupuncture combined with conven-tional drugs (ACCD) was superior to conventionaldrugs alone in reducing the incidence of acutemyocardial infarction (AMI) [OR=0.18, 95%CI (0.04,

0.84), P=0.03]. Moreover, ACCD was superior to con-ventional drugs in the relief of angina symptoms[OR=4.23, 95% CI (2.73, 6.56), P<0.00001], and im-provement of electrocardiography (ECG) [OR=2.61,95%CI (1.83, 3.73), P<0.00001]. Acupuncture by it-self was also superior to conventional drugs for angi-na symptoms [OR=3.59, 95%CI (1.76, 7.92),P=0.0004]and ECG improvement [OR=3.07, 95%CI (1.54, 6.10),P=0.001]. ACCD was superior to conventionaldrugs in shortening the time to onset of anginarelief [WMD=-1.40, 95% CI (-1.65, -1.15), P<0.00001]. However, the time to onset was signifi-cantly longer for acupuncture treatment than forconventional treatment alone [WMD=2.43, 95%CI(1.63, 3.23), P<0.000 01].

CONCLUSION: ACCD reduced the occurrence ofAMI, and both acupuncture and ACCD relieved an-gina symptoms and improved ECG. However, com-pared with conventional treatment, acupunctureshowed a longer delay before its onset of action.This indicates that acupuncture is not suitable foremergency treatment of heart attack. Owing to thepoor quality of the current evidence, the findingsof this systematic review need to be verified bymore RCTs to enhance statistical power.

© 2012 JTCM. All rights reserved.

Key words: Acupuncture therapy; Randomizedcontrolled trial; Efficacy; Review; Meta-analysis

INTRODUCTIONCoronary artery disease (CAD) commonly results fromatherosclerotic obstruction of coronary arteries andmostly manifests as angina pectoris and acute myocar-

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Chen J et al. Acupuncture therapy for angina pectoris: a systematic review

dial infarction. An ischemic heart disease, it is likely toattack people over 40 years of age. It has been reportedthat the incidence of angina pectoris is 0.1%-1% in Eu-ropean women aged 40%-54% years, and 2%-5% inmen of the same age group. The incidence is10%-15% in females and 10%-20% in males in peo-ple aged 65 to 74 years.1 With the rapid developmentof the Chinese economy, ischemic heart disease has be-come increasingly common in recent years. Accordingto a survey of a community in Beijing, the incidence ofangina pectoris and myocardial infarction is 30.7%(male 26.2%, female 33.7%) and 2.9% (male 4.8%, fe-male 1.7% ), respectively.2 It has been estimated thatthe global mortality of CAD will rise from 6.3 millionin 1990 to 11 million by the end of 2020, and that themortality will increase to 74.6% in the coming thirtyyears.3

Modern treatments to reduce ischemic symptoms andimprove prognosis of angina pectoris include nitrates,beta blockers, calcium antagonists, aspirin, and ACEinhibitors. These drugs can have undesirable effects.For instance, nitrate treatment carries the risks of toler-ance and rebound, and can cause headaches, flushedcheeks and other adverse reactions.4, 5

Acupuncture was recorded in Huang Di Nei Jing6 overtwo thousand years ago to work well in the treatmentof chest Bi syndrome (precordial pain). In more recentyears, acupuncture therapy for angina has occasionallybeen reported outside China. A non-randomized con-trolled trial in Denmark indicated that integrated reha-bilitation dominated by acupuncture reduced the riskof death in patients with coronary heart disease and de-creased their economic burden.7,8

Currently available randomized controlled trials(RCTs) have had small sample sizes and shown diverseoutcomes. The assessment and integration of these tri-als using an evidence-based approach to guide clinicaltreatment are of global priority. Therefore, in this sys-tematic review we synthesize the results of availableRCTs to assess the effectiveness and safety of acupunc-ture therapy for angina pectoris.

METHODS

Inclusion criteria for studiesAll RCTs, except those containing inaccurate or incom-plete data, were included.

Inclusion criteria for participantsParticipants had been diagnosed with angina pectorissince at least three months. Participants were excludedif they had acute myocardial infarction, severe arrhyth-mia, heart failure, hepatic failure or renal failure.

Inclusion criteria for the interventionsThis review included trials that made a comparison be-tween an acupuncture-dominated therapy and nitrates.The acupuncture-dominated treatments included acu-

puncture combined with conventional drugs (ACCD)and acupuncture itself. ACCD or acupuncture therapyconsisted of manipulations such as stimulation with fi-liform needles, and cupping after needling, and the du-ration of treatment was >10 days. We included studiesthat predominantly used nitrates as the conventionaltreatment. If they used other antianginal drugs, such asbeta-blockers or calcium antagonists, we included thetrial as long as the drugs were used equally across thecontrol and experimental groups.

Primary and secondary outcomesPrimary outcome: incidence ofmyocardial infarction.Secondary outcomes: 1) improvement of angina symp-toms; 2) time to onset of angina relief in response to treat-ment; and 3) electrocardiography (ECG) improvement.

Search methodsWe searched the following databases: Academic SourcePremier (1975 to August 2011), MEDLINE (1993 toAugust 2011), Science Citation Index Expanded (1973to August 2011) and the three Chinese databases Chi-na biology medicine (1978 to August 2011), China na-tional knowledge infrastructure (1979 to August 2011)and VIP database for Chinese technical periodicals(1989 to August 2011). Studies published in both Eng-lish and Chinese were retrieved. Further, studies includ-ed in reference lists of relevant trials and reviews werealso identified. The following key words were used inthe search: angina, angina pectoris, coronary heart dis-ease, acupuncture, and electroacupuncture. A sampleretrieval strategy for MEDLINE is shown below.1) acupuncture therapy.mp. or expAcupunctureTherapy2) electroacupuncture. mp. or exp Electroacupuncture3) electric acupuncture.mp. or expElectric Acupuncture4) electric stimulat$.tw.5) transcutaneous electrical nerve stimulation6) tens.mp7) or/1)-6)8) angina pectoris.mp. or exp Angina Pectoris9) angina.mp.10) stable angina.mp.11) unstable angina.mp.12) or/8)-11)13) 7) and 12)14) randomized controlled trial.pt.15) controlled clinical trial.pt.16) randomized controlled trials.sh.17) random allocation.sh.18) double blind method.sh.19) single-blind method.sh.20) or/14)-19)21) (animals not human).sh.22) 20 not 2123) clinical trial.pt.24) exp clinical trials25) (clin$ adj25 trial$).ti,ab.26) ((singl$ or doubl$ or trebl$ or tripl$) adj25 (blind$ or mask$)).ti,ab.

495



27) random$.ti,ab.28) research design.sh.29) or/23-2830) 29) not 21)31) 30) not 21)32) comparative study.sh.33) exp evaluation studies34) follow up studies.sh.35) prospective studies.sh.36) (control$ or prospectiv$ or volunteer$).ti,ab.37) or/32)-36)38) 37) not 21)39) 38) not 22) or 31)40) 22) or 31) or 39)41) 13) and 40)

Data collection and extractionRCTs evaluating the efficacy of acupuncture-dominat-ed therapy for angina pectoris were included. Titlesand abstracts of searched studies were screened for fur-ther review. Those that appeared eligible were deter-mined eligible by review of the full text. The inclusioncriteria were applied by two authors independently.Disagreements were resolved by discussion and by con-sultation with other authors of our group, and a judg-ment was made based on consensus.Data were collected independently by two authors us-ing a piloted data extraction form. The following char-acteristics of the trials were recorded on the form: de-sign, methods, participants, interventions, and out-comes. Any disagreements were resolved by referring tothe trial report and by discussion. The standards ad-vised by the Cochrane handbook9 in terms of random-ization, allocation concealment, binding, complete da-ta and selective reporting were employed to evaluatethe quality of the RCTs. "Yes", "No" or "not-reported"were used to determine the standards mentionedabove. The quality of each study was assessed as lowrisk of bias (one or more criteria not met), as moderaterisk of bias (one or more criteria partly met), or as highrisk of bias (all of the criteria met).For dichotomous outcomes, the number of partici-pants experiencing the event in each group was record-ed. For continuous outcomes, the means and standarddeviations for each group were extracted. Data entriesin RevMan 5.1 (free software downloadable from http://ims.cochrane.org/revman/download) were dou-ble-checked.

Statistical analysisData were used for a meta-analysis if they were avail-able, of sufficient quality and sufficiently similar. Di-chotomous data were expressed as relative risks (OR).Continuous data were expressed as weighted mean dif-ferences (WMD). Overall results were calculated basedon the fixed effects model when no heterogeneity wasfound among pooled studies. Where heterogeneity ex-isted, the random effects model was used. Heterogene-

ity was tested using the Z score and the Chi-square sta-tistics with significance set at P<0.1. Possible sources ofheterogeneity were assessed by sensitivity and subgroupanalyses as described below.

RESULTS

Description of included studiesWe selected 21 studies out of the 296 relevant referenc-es by screening titles and reviewing full texts. The dataof the included studies were extracted using a formthat included study design, sample size, interventionand outcome measure (Figure 1).

General data of included studiesSixteen independent studies were reported in the 21 in-cluded articles. The treatment groups received eitherACCD or acupuncture therapy, while the controlgroups were treated with conventional drugs. The num-ber of participants varied from 49 to 200 and the dura-tion of treatment was between 10 days and 6 weeks(Table 1).

Quality assessment of included studiesSix of the included articles reported their method ofrandomization, whereas none mentioned allocationconcealment, blinding, loss of follow-up or drop-out,or selective report. All studies were assessed as having ahigh or moderate risk of bias (Table 2).

Effect of ACCD on the incidence of myocardialinfarctionTwo papers reported their follow-up of participantswith myocardial infarction.21,26 In those trials, the pa-tients received ACCD together with the same conven-tional drugs as the control group, and there was littleheterogeneity between the two studies (P=1.00, I2=0%). Meta-analysis was conducted using the fixed ef-fect model. The result indicated that ACCD was bet-ter than conventional treatment for preventing acutemyocardial infarction [OR=0.18, 95%CI (0.04, 0.84),P=0.03] (Figure 2).

Effects of ACCD and acupuncture on anginasymptomsTen studies reported the effective rate of angina reliefby ACCD.11-13,16,20-22,26,30 There was little heterogeneityamong these studies (P=0.95, I2 =0%), so meta-analysiswas conducted using the fixed effect model.The result in-dicated that ACCD was superior for improvement of an-gina symptoms compared to the conventional treatment[OR=4.23, 95%CI (2.73, 6.56),P<0.00001] (Figure 3).Two studies reported the effective rate of angina reliefby acupuncture.27,28 There was little heterogeneity be-tween the two studies (P=0.35, I2 = 0%), so meta-analy-sis was conducted using the fixed effect model. The re-sult indicated that acupuncture was superior compared

496



Table 1 Characteristics of included studies

Notes: A: acupuncture; CT: conventional treatment; T: treatment group; C: control group.

Study

Yuan ZJ10

Wang X11

Cao JP12

Liu WP13

Liu WP14

Liu WP15

Chang PF16

Tong YH18

Tong YH19

Tong YH20

Huang FQ17

Xu FH21

Yu SH22

Li CP23

Xu GD25

Liu WP24

Zhou W27

Zhai WS26

Yin LH28

Yin LH29

Lin Z30

n

T C

30 28

28 21

30 21

32 31

32 30

32 30

30 22

120 80

80 60

120 80

80 60

35 35

33 30

36 34

120 80

32 30

72 56

35 35

40 38

40 38

35 30

Intervention

T C

A+CT CT

A+CT CT

A+CT CT

A+CT CT

A+CT CT

A+CT CT

A+CT CT

A+CT CT

A+CT CT

A+CT CT

A+CT CT

A+CT CT

A+CT CT

A+CT CT

A+CT CT

A+CT CT

A CT

A+CT CT

A CT

A CT

A+CT CT

Drugs employed as conventional treatment

isosorbide 5-mononitrate

isosorbide 5-mononitrate, betaloc, aspirin

isosorbide dinitrate, aspirin

isosorbide dinitrate

isosorbide 5-mononitrate, diltiazem hydrochloride, aspirin

isosorbide 5-mononitrate, diltiazem hydrochloride, aspirin

nitrates, betaloc

isosorbide 5-mononitrate, betaloc, simvastatin, aspirin




nitrates, beta-blocker, calcium antagonist, aspirin

Nitrates

isosorbide 5-mononitrate, betaloc, aspirin


isosorbide 5-mononitrate, diltiazem hydrochloride , aspirin

isosorbide dinitrate, betaloc, aspirin

nitrates, beta-blocker, calcium antagonist, aspirin



isosorbide 5-mononitrate, aspirin

Course

4 weeks

2 weeks

3weeks

8 weeks

4 weeks

4 weeks

2 weeks

6 weeks

6 weeks

6 weeks

6 weeks

10 days

2 weeks

24 sessions

6 weeks

4 weeks

6 weeks

10 days

30 sessions

30 sessions

4 weeks

Figure 1 Flow diagram of the search method and selection processASP: academic source premier; SCI-E: science citation index expanded; CBM: China biology medicine; CNKI: China national knowl-edge infrastructure; VIP: VIP database for Chinese technical periodicals.

Relevant reference（n=296）ASP (n=13)MEDILINE(n=19)SCI-E（n=14）CBM（n=35）CNKI（n=184）VIP（n=31）

Review titles and abstract：duplication-elimination（n=62）non-conforming articles（n=181）

Articles proposed to include(n=53)

In-depth review of the full-text:non-conforming articles（n=32）

Final included studies(n=21)

497



with the conventional treatment in reducing anginasymptoms [OR=3.59, 95%CI (1.76, 7.92), P=0.0004](Figure 4).

Effect of ACCD and acupuncture on the time toonset of angina reliefTwo studiesreported the time to onset of angina relief pro-vided by ACCD.11,22 There was little heterogeneity be-tween the two studies (P=1.00, I2=0% ), so meta-analysis

wasconductedusingthefixedeffectmodel.Theresultindi-cated thatACCDshortened the time toonset of angina re-lief compared with conventional treatment [WMD=-1.40, 95%CI (-1.65, -1.15), P<0.00001] (Figure 5).Only one study reported the effect of acupuncture onthe time to onset of angina relief.27 The fixed effectmodel was employed to conduct meta-analysis inwhich no combined effect was applied. The resultshowed that acupuncture had a slower onset of action

Table 2 Methodological quality assessment of included studies

Study

Yuan ZJ 10

Wang X 11

Cao JP 12

Liu WP13

Liu WP14

Liu WP15

Chang PF16

Huang FQ17

Tong YH18

Tong YH19

Tong YH20

Xu FH21

Yu SH22

Li CP23

Liu WP24

Xu GD25

Zhai WS26

Zhou W27

Yin LH28

Yin LH29

Zhang L30

Method ofrandomization

Unclear

Unclear

Yes (coin toss)

Unclear

Yes (random number table)


Unclear

Unclear

Unclear

Unclear

Unclear

No (medical record number)

Unclear


Unclear

Unclear

Unclear

Unclear

Yes (computer-generatingrandom numbers)

Yes (computer-generatingrandom numbers)

Unclear

allocation con-cealment

not reported

not reported

not reported

not reported

not reported

not reported

not reported

not reported

not reported

not reported

not reported

not reported

not reported

not reported

not reported

not reported

not reported

not reported

not reported

not reported

not reported

blinding

not reported

not reported

not reported

not reported

not reported

not reported

not reported

not reported

not reported

not reported

not reported

not reported

not reported

not reported

not reported

not reported

not reported

not reported

not reported

not reported

not reported

Loss of follow-upor drop-out

non

non

non

non

non

non

non

non

non

non

non

non

non

non

non

non

non

non

non

non

non

Selectivereport

non

non

non

non

non

non

non

non

non

non

non

non

non

non

non

non

non

non

non

non

non

Quality assess-ment

high risk

high risk

moderate risk

high risk

moderate risk

moderate risk

high risk

high risk

high risk

high risk

high risk

high risk

high risk

moderate risk

high risk

high risk

high risk

high risk

moderate risk

moderate risk

high risk

Figure 2 Forest plot of ACCD for acute myocardial infarctionACCD: acupuncture combined with conventional drugs.

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Figure 6 Forest plot of the effect of acupuncture on the time to onset of angina relief

Figure 7 Forest plot of the efficacy of ACCD in improving ECGACCD: acupuncture combined with conventional drugs; ECG: electrocardiography.

Figure 4 Forest plot of acupuncture for effective improvement of angina symptoms

Figure 5 Forest plot of the effect of ACCD in reducing the time to onset of angina reliefACCD: acupuncture combined with conventional drugs.

Figure 3 Forest plot of ACCD for effective improvement of angina symptomsACCD: acupuncture combined with conventional drugs.

499



compared to nitrates [WMD=2.43, 95%CI (1.63, 3.23),P<0.000 01] (Figure 6).

Effects of ACCD and acupuncture on ECGimprovementTen studies reported the efficacy of ACCD on ECG im-provement.10-12,16,20,21,23,26,30 There was little heterogeneityamong these studies (P=0.36, I2=8%), so meta-analysiswas conducted using the fixed effect model.The result in-dicated that ACCD was superior compared to the con-ventional treatment for the improvement of ST segmentischemia [OR=2.61, 95%CI (1.83, 3.73), P<0.000 01](Figure 7).Two studies reported the efficacy of acupuncture inECG improvement.27,28 There was little heterogeneityamong these studies (P=0.93, I2=0%), so meta-analysiswas conducted using the fixed effect model. The resultindicated that acupuncture was superior comparedwith the conventional treatment for the improvementof ST segment ischemia [OR=3.07, 95% CI (1.54,6.10), P=0.001] (Figure 8).

Assessment of publication biasudging from to the symmetry of the funnel plot, no ap-parent publication bias was found in the meta-analysis,indicating that the results are reliable (Figure 9).

Adverse effectNone of the studies reported any adverse effects associ-ated with acupuncture therapy.

DISCUSSIONAll current randomized controlled trials were conduct-

ed in China, and all patients were Chinese. The articleswere all published in Chinese journals. Nitrate treat-ment was given to all control groups. This typical andpopular vasodilator has been proven to be effective inthe treatment of angina pectoris, as reported by a sys-tematic review abroad.31 Based on our analysis, acu-puncture-dominated therapy appears beneficial fortreating angina pectoris, as it relieves symptoms, pro-vides pain relief, and promotes ECG restoration. How-ever, acupuncture shows a slower time to onset thanconventional treatment and is therefore not advised forthe emergency treatment of ischemic disease.The main shortcoming of the conclusions of our studyis the poor quality of the original studies, as this is like-ly to influence the reliability of our results. It also sug-gests that there is a need for medical staff in China toimplement further improvements in terms of the de-sign and methodology of clinical studies. Moreover,more RCTs with larger samples are needed to validatethe use of acupuncture in angina treatment.Our study indicates that ACCD can play an active rolein preventing acute myocardial infarction, whichwould lead to improvements in the life quality of pa-tients. In addition, when compared to the controlgroup, ACCD or acupuncture treatment increased theoverall efficacy in terms of symptom relief and ECGimprovement. When the time to onset of angina reliefwas used as an outcome measure, ACCD was superiorto the conventional treatment alone, whereas acupunc-ture showed a slower onset of action. In conclusion,acupuncture therapy is indicated for treating stable an-gina pectoris, but it is unsuitable for the treatment ofpatients with an acute ischemic heart event.

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Figure 8 Forest plot of the effect of acupuncture on ECG improvementECG: electrocardiography.

Figure 9 Funnel plot of the included studies on the effectson ECG improvementECG: electrocardiography.

SE (log[OR])0

0.2

0.4

0.6

0.8

10.02 0.1 1 10 50

OR

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