Efficacy and safety of Yinchenwuling powder for ...ject word for hyperlipidemia as "Hyperlipidemias" and free texts as Hyperlipemia, Hyperlipemias, Hyperlipid-emia, Lipidemia, Lipidemias,

JTCM |www. journaltcm. com April 15, 2016 |Volume 36 | Issue 21 |

Online Submissions: http://www.journaltcm.com J Tradit Chin Med 2016 April 15; 36(2): [email protected] ISSN 0255-2922

© 2016 JTCM. All rights reserved.

SYSTEMATIC REVIEW

Efficacy and safety of Yinchenwuling powder for hyperlipidemia: asystematic review and Meta-analysis

Yao Haiqiang, Zhang Zengliang, Wang Ji, Zuo Jiacheng, Chen Yu, Zhu Libing, Li Xiaoke, Yang Zheng, WangZisong, Sun Ranran, Xu Xuanxuan, Li Changming, Wu Yanling, Li Lingru, Wang Qiaa

Yao Haiqiang, Wang Ji, Libing Zhu, Li Xiaoke, YangZheng, Wang Zisong, Sun Ranran, Xu Xuanxuan, LiChangming, Wu Yanling, Li Lingru, Wang Qi, Basic Medi-cal College, Beijing University of Chinese Medicine, Beijing100029, ChinaZhang Zengliang, Traditional Chinese Medicine College, In-ner Mongolia Medical University, Hohhot 010110, ChinaChen Yu, Department of Nutrition, Chinese-Japan Friend-ship Hospital, Beijing 100029, ChinaSupported by the Chinese National Natural Science Foun-dation Key Project (Identification of the Molecular SignatureContributing to the Susceptibility of Phlegmatic HygrosisConstitution to Metabolic Syndrome, No. 81030064)Correspondence to: Li Lingru and Wang Qi, Basic MedicalCollege, Beijing University of Chinese Medicine, Beijing100029, China. [email protected]; [email protected]: +86-10-64286766Accepted: December 3, 2015

AbstractOBJECTIVE: To assess the clinical effectiveness andadverse effects of Yinchenwuling powder (YCWLP)in the treatment of hyperlipidemia using Meta-anal-ysis.

METHODS: Seven electronic databases weresearched for randomized controlled trials designedto evaluate the clinical effectiveness of YCWLP forhyperlipidemia published in any language prior toFebruary 2015. Two reviewers independently identi-fied articles, extracted data, assessed quality, andcross-checked the results. Revman 5.3 was used toanalyze the data.

RESULTS: Only five randomized controlled trialswith poor methodology were included in the analy-

sis. The five trials compared YCWLP with conven-tional lipid-lowering drugs. Meta-analysis indicatedthat YCWLP was more effective at the levels of totalcholesterol and triglycerides, while increasing thelevel of high-density lipoprotein cholesterol with-out serious adverse effects. However, it was notmore effective than lipid-lowering drugs in reduc-ing low-density lipoprotein cholesterol and improv-ing hemorheology.

CONCLUSION: YCWLP appeared to improve lipidlevels. However, given the high risk of bias amongthe trials, we could not conclude that YCWLP wasbeneficial to patients with hyperlipidemia. More rig-orous trials are required to provide stronger evi-dence for the conclusion.

© 2016 JTCM. All rights reserved.

Key words: Hyperlipidemias; Review; Meta-analy-sis; Yinchenwuling powder; Randomized controlledtrials

INTRODUCTIONHyperlipidemia refers to elevated lipid levels in blood.1

The condition is also called hyperlipemia, lipemia, orlipidemia, and includes elevated total cholesterol (TC),low-density lipoprotein cholesterol (LDL-C), and totaltriglyceride (TG) levels in the blood.2 Hyperlipidemiais a major risk factor for cardiovascular and cerebrovas-cular disease.3,4 Hyperlipidemia can induce atherosclero-sis, which can lead coronary heart disease, stroke, andmyocardial infarction.5,6 Approximately 33.5% of theadult population in the United States has elevated se-rum cholesterol levels, and millions of people world-

135


Yao HQ et al. / Systematic Review

wide are affected.7 The incidence of hyperlipidemia isgradually increasing, and may worsen with an agingpopulation. Therefore, the prevention and manage-ment of hyperlipidemia is important.8 Hypolipidemicagents commonly used in clinic include polyene unsat-urated fatty acids, statins, fibrates, nicotinic acids, ezeti-mibe, probucol, and other compound preparations.9

However, almost all of the main lipid-lowering drugscause side effects. For instance, statins cause myopathyin approximately 10% of patients receiving treat-ment.10 An estimated 20% of patients are statin-resis-tant or intolerant;11 novel treatments are therefore re-quired.In several Asian countries, such as China, Korea, andJapan, herbs have been widely used in the treatment ofhyperlipidemia. The etiology and pathogenesis of hy-perlipidemia in Traditional Chinese Medicine (TCM)is pathogenic dampness, a TCM symptom patternidentified in terms of TCM's theory. Because of bodyfluid Metabolic disturbances, excessive phlegm-damp-ness stays within the body, affecting blood circulationand causing hyperlipidemia.12,13 Based on the symptompattern identified, and experience from the manage-ment of hyperlipidemia with TCM, a specific formula,Yinchenwuling powder, was developed. YCWLP iscomposed of: Yinchen (Herba Artemisiae Frigidae),Guizhi (Ramulus Cinnamomi), Fuling (Poria), Baizhu(Rhizoma Atractylodis Macrocephalae), Zexie (RhizomaAlismatis), and Zhuling (Polyporus). YCWLP is widelyused alone or combined with lipid-lowering drugs totreat hyperlipidemia in China. Recent studies haveshown that YCWLP could obviously decrease the levelsof TC, TG, and LDL, increase high-density lipopro-tein cholesterol (HDL), reduce blood viscosity, packedcell volume, and platelet adhesion rate, maintain aortastructure, and lower bcl-2 mRNA expression.14,15 Fur-thermore, several clinical studies have reported effec-tiveness of YCWLP. These studies range from case re-ports and case series to controlled observational studiesand randomized clinical trials. However, critically ap-praised evidence is not yet available, including system-atic reviews or Meta-analyses. Therefore, we aimed toevaluate the beneficial and harmful effects of YCWLPfor hyperlipidemia in randomized controlled trials.

METHODS

The protocol of this study was registered in the PROS-PERO International prospective register of systematicreviews (http://www.crd.york.ac.uk/PROSPERO/dis-play_record.asp?ID=CRD42015019428).

Inclusion criteriaTypes of study. All randomized controlled clinical trials(RCTs) that assessed the effect of YCWLP for hyperlip-idemia were included with no language restrictions. Allmodified YCWLP combinations were also included.

No restrictions on the population characteristics, lan-guage, or publication type were imposed.Types of participant. Patients with hyperlipidemia whowere diagnosed with the criteria of "Screening andmanagement of lipids"6 and any other studies deemedreasonable were included regardless of age, sex, or raceof the study participants.Outcome measures. The primary outcome measureswere: TC, TG, LDL, HDL, and adverse events. Thesecond outcome indexes were effective rate and hemo-dynamic indexes, including high shear rate blood vis-cosity, low shear rate blood viscosity, and plasma viscos-ity. The curative effect valuation standards were mainlydetermined according to the "Chinese Adult Dyslipid-emia Prevention Guide."17 "Effective rate" was definedas TC decreasing by > 10%, TG decreasing by > 20%,or restoration of one of the lipid indexes to normal af-ter intervention. "Invalid" was defined as TC decreas-ing by < 10%, TG decreasing by < 20%, or restorationof none of the lipid indexes to normal after interven-tion. "Worsened" was defined as TC or TG increasingby > 10%, or other lipid indexes exceeding the normallevels after intervention.

Search strategyLiterature searches were conducted in the three Englishelectronic databases: Cochrane Central Register ofControlled Trials (CENTRAL) in the Cochrane Li-brary, PubMed, EMBASE, and four Chinese databases:Chinese Biomedical Literature Database (CBM), Chi-nese National Knowledge Infrastructure (CNKI), Chi-nese Scientific Journal Database (VIP), and the Wang-fang Database for publications dating up to February2015. First, we checked the subject headings throughMesh database in MEDLINE and we found the sub-ject word for hyperlipidemia as "Hyperlipidemias" andfree texts as Hyperlipemia, Hyperlipemias, Hyperlipid-emia, Lipidemia, Lipidemias, Lipemia, and Lipemias.There was no subject word for Yinchenwuling powder,so we just used the free text as "yinchen wuling" and"yin chen wu ling." Finally, we formulated the litera-ture search formula for PubMed as follows:#1: (Hyperlipidemias[MeSH Terms]) OR Hyperlipe-mia[Title/Abstract]) OR Hyperlipemias[Title/Ab-stract]) OR Hyperlipidemia[Title/Abstract]) OR Lipid-emia[Title/Abstract]) OR Lipidemias[Title/Abstract])OR Lipemia[Title/Abstract]) OR Lipemias[Title/Ab-stract]#2: ("yinchen wuling" [Title/Abstract]) OR "yin chenwu ling" [Title/Abstract]#3: Random[Title/Abstract]#4: #1 and #2 and #3When searching in Chinese databases, we first checkedCBM and VIP to retrieve synonyms, and then we for-mulated the search formula as: ("Gao Zhi Xue Zheng"or "Gao Xue Zhi Zheng" or "Gao Dan Bai XueZheng" or "Gao Dan Gu Chun Xue Zheng" or "GaoGan You San Zhi Xue Zheng") and ("Yin Chen Wu

136



Ling Sa"). However, the specific search procedure var-ied in some cases given the different interface settingsof each database.The bibliographies of included studies were alsosearched for additional references. Academic annualconference proceedings (from 2010 to 2015) of threechapters of China Association of Chinese Medicine,namely the Internal Medicine Chapter, Heart DiseaseChapter, and Zhongjing Doctrine Chapter, weresearched manually to identify additional studies. Wesearched the seven databases for target articles with noresearch type limitations. Gray literature or ongoingstudies were not included.

Data extraction and quality assessmentTwo reviewers (HY and JZ) independently identifiedthe articles according to the established inclusion crite-ria and extracted data for collection. The extracted dataincluded the authors and title of the study, year of pub-lication, sample size, and age and sex of the partici-pants, as well as details of methodological informationand control interventions. Chinese herbs, treatmentprocess, outcomes, and adverse effects were also includ-ed. Disagreements were resolved by discussion and con-sensus as mediated by a third reviewer (ZZ). The meth-odological quality of the trials was assessed using sevencriteria from the Cochrane Handbook for SystematicReview of Interventions, Version 5.10 (HY).18 Theitems included random sequence generation (selectionbias), allocation concealment (selection bias), blindingof participants and personnel (performance bias), blind-ing of outcome assessment (detection bias), incompleteoutcome data (attrition bias), selective reporting (re-porting bias), and other types of bias. Three levels wereused to evaluate the trials: low risk of bias (all the itemswere in low risk of bias), high risk of bias (at least oneitem was in high risk of bias), and unclear risk of bias(at least one item was in unclear).

Data analysisRevMan 5.3 software (ver. 5.3 RevMan, Copenhagen,Denmark)19 provided by Cochrane Collaboration wasused for data analyses. The odds ratio (OR) of data wascalculated if the variables were dichotomous data, andthe weighted mean difference (WMD) was calculatedif the variables were continuous data, respectively, with95% confidence intervals (CI). Heterogeneity betweentrials was identified by the Chi-squares (χ2) test. Whenthere was acceptable homogeneity (P > 0.1, I 2 ≤ 50%),the fixed effect model was used for Meta-analysis.When heterogeneity was significant (P ≤ 0.1, I 2 >50%), the random effect model was used.18

RESULTS

Description of studiesSixty-eight relevant articles were identified andscreened, and only 32 remained after duplicate records

were deleted. After screening the titles and abstracts,19 articles were excluded. Fifteen were excluded be-cause they were not clinical trials, three were excludedbecause their study focus was not only hyperlipidemia,and one was excluded because it did not involve YC-WLP. After reviewing the full texts, three were exclud-ed because they lacked detailed data and only reporteddifferences between the treatment and control groupsafter intervention. Another three were excluded be-cause they were case reports or lacked a comparisongroup. One study was excluded because hyperlipidemiawas only a complication and lipids were not the mainevaluating indexes. Another study was excluded be-cause YCWLP was combined with simvastatin and wasnot used alone in the trial. Therefore, five studies wereincluded in the final analysis.20-24 The flow diagram ofthe abovementioned process is shown in Figure 1.All five RCTs were conducted in China and publishedin Chinese between 2001 and 2012. The characteris-tics of those randomized trials are summarized in Table1. A total of 363 patients were involved in the five tri-als, and two different diagnosis criteria were followed.One trial20 used the "Chinese Adult Dyslipidemia Pre-vention Guide" (2007 edition), whereas another trial23

used the criteria made by the Geriatrics Research col-laborative group in the National Administration of Tra-ditional Chinese Medicine. The remaining three tri-als21,22,24 only described patients with hyperlipidemiaand did not mention definite diagnostic criteria. All in-cluded trials used YCWLP alone as the treatment mea-sure. Among the five trials, one trial20 used simvastatinas the control intervention, one trial21 used atorvas-tatin, one trial23 used gypenoside, and the two remain-ing trials22,24 used hexanicotol. The treatment durationof the five trials was inconsistent. Four trials20,21,23,24 last-ed for 4 weeks, and one22 lasted for 12 weeks. Other de-tails are presented in Table 1.

Risk of bias in included studiesAfter evaluation, all studies included have a high riskof bias and were considered of poor methodologicalquality. All trials claimed that participants were ran-domly allocated, but only one study20 stated the specif-ic method of sequence generation as random numbertable. The other four trials reported no detailed infor-mation. Therefore, we could not evaluate the appropri-ateness of their methods. The allocation concealment,as well as the blinding of participants and personnel,was not mentioned in all trials. None of the trials pro-vided information about dropouts or withdrawals. Allof the included studies appeared to have adequate andacceptable compliance. Selective reporting was general-ly unclear because of the inaccessibility to the studyprotocol. Other bias may exist but could not be con-firmed given the lack of sufficient evidence. No con-tact information was provided in the five articles.Therefore, we were unable to obtain more details fromthe authors (Figures 2 and 3).

137



Effective rateAll five trials used YCWLP as the treatment group ver-sus anti-lipemic agents as the control group. Three tri-als21,23,24 used effective rate as an evaluation index, butthe criteria they used to define effective were not entire-ly consistent. In the study by Zhang,21 effective was de-fined as "TC reduced by ≥ 10% , TG reduced by ≥20% , or HDL increased by ≥ 0.10 mmol/L." In thestudy by Wang et al.,23 the effective criteria was "TC re-duced by ≥ 10%, TG reduced by ≥ 20%, or HDL in-creased by ≥ 4 mg/dL," whereas the criteria was "TC re-duced by ≥ 10% or TG reduced by ≥ 20% " in thestudy by Kang.24 The three independent trials showedhomogeneity in the results (P = 0.80, I 2 = 0%). There-fore, we used a fixed-effects model to analyze the dataand confirmed that YCWLP had a significantly im-proved clinical effective rate as compared with the con-trol group (OR=3.57; 95%CI = [1.49, 8.51]) (Figure 4).

TCAll five studies compared the effect of lowering TC be-tween the treatment and control groups, but theyshowed heterogeneity (P < 0.00001, I 2 = 96%). Afterconducting the sensitivity analysis, we excluded thestudy by Hu (2012). The data then showed acceptablehomogeneity (P = 0.18, I 2 = 39%), so the fixed-effectsmodel was used to pool the data. A forest plot demon-strated that the treatment group was significantly moreeffective than the control group［(MD = −0.50; 95%CI = (−0.53, −0.47)] (Figure 5).

TGAll five studies used TG as an outcome measurement,but they showed significant heterogeneity (P = 0.02;I 2 = 66%). The study by Wang et al.23 (P = 0.55; I 2 =0% ) was excluded, and the fixed-effects model wasused to conduct the statistical analysis. YCWLP had a

68 records identifiedthrough database

searching

0 additional recordsidentified through

other sources

32 records after duplicates removed

32 records screened

19 records excluded:Animal study, literature review or

theoretical research (n = 15)Not about YCWLP (n = 1)

Not about hyperlipidemia (n = 3)

13 full-text articlesassessed for eligibility

8 full-text articles excluded, with reasons:Lack of detailed data (n = 3)

Case reports or case series (n = 3)Lipid is not the main evaluating index (n = 1)

The intervention was not YCWLP alone (n = 1)

5 studies included inqualitative synthesis

5 studies includedin quantitative

synthesis(Meta-analysis)

Figure 1 Study flow diagramYCWLP: Yinchenwuling power

138



Tabl

e1

Char

acte

ristic

sof

incl

uded

stud

ies

Stud

y

Hu

Y20

1220

Zha

ngN

2011

21

Liu

YLet

al20

0422

Wan

gD

Set

al20

0123

Kan

gX

X20

0024

Sam

ple

(T/C

)

135

(68/

67)

40(2

0/20

)

36(2

1/15

)

60(3

0/30

)

92(4

6/46

)

Age

(T/C

)

(44.

0±

4.21

)/(4

2.7

±3.

21)

45-6

5

40-6

0

(57.

03±

8.05

)/(5

9.07

±6.

76)

55.4

/56

Gen

derM

:F(T

/C)

(40∶

28)/

(48∶

19)

22∶

18

19∶

17

(23∶

7)/(

21∶

9)

(30∶

16)/

(31∶

15)

Inte

rven

tion

YCW

LP

YCW

LP

YCW

LP

YCW

LP

YCW

LP

Con

trol

simva

statin

ator

vasta

tin

hexa

nico

tol

gype

nosid

e

hexa

nico

tol

Cou

rse

(wee

k)

4 4 12 4 4

Out

com

em

easu

re

TC

,TG

,HD

L,LD

L,hi

ghsh

earr

ate

bloo

dvi

scos

ity,l

owsh

earr

ate

bloo

dvi

scos

ity,p

lasm

avi

scos

ity,e

ryth

rocy

teas

sem

blin

gin

dex,

eryt

hroc

yte

defo

rmat

ion

inde

x

TC

,TG

,HD

L

TC

,TG

,HD

LTC

,TG

,HD

L,LD

L,hi

ghsh

earr

ate

bloo

dvi

scos

ity,l

owsh

earr

ate

bloo

dvi

scos

ity,p

lasm

avi

scos

ity,e

ryth

rocy

tese

dim

enta

tion

rate

,er

ythr

ocyt

eel

ectro

phor

esis,

hem

atoc

rit,f

ibrin

ogen

TC

,TG

Effe

ctiv

era

te(T

/C)

NM

T

(19∶

20)/

(17∶

20)

NM

T

(28∶

30)/

(26∶

30)

(41∶

46)/

(30∶

46)

Side

effe

cts

(T/C

)

4/30 0/1

NM

T

NM

T

0/6

Not

es:T

/C:t

reat

men

tgro

up/c

ontro

lgro

up;M

/F:m

ale/

fem

ale;

YCW

LP:Y

inch

enw

ulin

gpo

wde

r;TC

:tot

alch

oles

tero

l;TG

:trig

lyce

rides

;LD

L:lo

w-d

ensit

ylip

opro

tein

chol

este

rol;

HD

L:hi

gh-d

ensit

ylip

opro

-te

inch

oles

tero

l;N

MT:

notm

entio

ned.

Stud

ies

Hu

Y20

1220

Zha

ngN

2011

21

Liu

YLet

al20

0422

Wan

gD

Set

al20

0123

Kan

gX

X20

0024

Form

ula

YCW

LP

YCW

LP

YCW

LP

YCW

LP

YCW

LP

Pres

crip

tion

Yinc

hen

(Her

baAr

tem

isiae

Frig

idae

)20

g,Ze

xie

(Rhi

zom

aAl

ismat

is)10

g,Zhu

ling

(Pol

ypor

us)1

0g,

Fulin

g(P

oria

)10

g,Ba

izhu

(Rhi

zom

aAt

racty

lodi

sMac

roce

phal

ae)1

0g,

Gui

zhi(

Ram

ulus

Cin

nam

omi)

6g

Yinc

hen

(Her

baAr

tem

isiae

Frig

idae

)10

g,Zhu

ling

(Pol

ypor

us)1

0g,

Fulin

g(P

oria

)10

g,Ze

xie

(Rhi

zom

aAl

ismat

is)15

g,Ba

izhu

(Rhi

zom

aAt

racty

lodi

sMac

roce

phal

ae)1

0g,

Gui

zhi(

Ram

ulus

Cin

nam

omi)

5g,

Hua

ngqi

(Rad

ixAs

traga

liM

ongo

lici)

10g,

Hon

g-hu

a(F

losC

arth

ami)

15g,

Shan

zha

(Fru

ctusC

rata

egiP

inna

tifid

ae)1

5g

Yinc

hen

(Her

baAr

tem

isiae

Frig

idae

)50

g,Fu

ling

(Por

ia)1

0g,

Zexi

e(R

hizo

ma

Alism

atis)

20g,

Zhu

ling

(Pol

ypor

us)1

0g,

Baizh

u(R

hizo

ma

Atra

ctylo

disM

acro

ceph

alae

)10

g,G

uizh

i(Ra

mul

usC

inna

mom

i)5

g

NM

T

Yinc

hen

(Her

baAr

tem

isiae

Frig

idae

)30

g,Ze

xie

(Rhi

zom

aAl

ismat

is)9

g,Fu

ling

(Por

ia)15

g,Zhu

ling

(Pol

ypor

us)9

g,Ba

izhu

(Rhi

zom

aAt

racty

lodi

sM

acro

ceph

alae

)10

g,G

uizh

i(R

amul

usC

inna

mom

i)6

g,Sh

anzh

a(F

ructu

sC

rata

egi

Pinn

atifi

dae)

10g,

Dan

shen

(Rad

ixSa

lvia

eMilt

iorr

hiza

e)15

g

Taki

ngin

struc

tion

deco

ctio

n,or

alta

k-en

,tw

ice

ada

y

gran

ule,

oral

take

n,th

ree

times

ada

y

deco

ctio

n,or

alta

k-en

,tw

ice

ada

y

deco

ctio

n

deco

ctio

n,or

alta

k-en

,tw

ice

ada

y

Tabl

e2

Inte

rven

tion

deta

ilsof

incl

uded

stud

ies

Not

es:Y

CW

LP:Y

inch

enw

ulin

gpo

wde

r;N

MT:

notm

entio

ned.

139



better effect on lowering the TG than that of the lip-id-lowering drugs [MD = －0.12; 95% CI = (－0.14,－0.10)] (Figure 6).

HDLFour studies20-23 reported a comparison of HDL be-tween the treatment group and the control group afterintervention. The data of the four trials showed homo-

geneity (P = 0.85, I 2 = 0%). Therefore, the fixed-effectmodel was used. Meta-analysis demonstrated that YC-WLP was more effective than lipid-lowering drugs inincreasing HDL [MD = 0.07; 95% CI = (0.03, 0.11)](Figure 7).

LDLOnly two studies20,23 compared the effect of lowering

Random 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 reporting (reporting bias)

Other bias

Low risk of bias Unclear risk of bias High risk of bias

0% 25% 50% 75% 100%

Figure 2 Risk of bias graph

Random 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 reporting (reporting bias)

Other bias

Hu

2012

Kang

2000

Liu2004

Wang

2001

Zhang

2011

Figure 3 Risk of bias summary

Figure 4 Effective rate of Yinchenwuling power versus lipid-lowering drugs

Figure 5 Total chole sterol of Yinchenwuling power versus lipid-lowering drugs

140



LDL between treatment and experimental group afterintervention. The data showed significant heterogene-ity (P = 0.009, I 2 = 85%), therefore, the random ef-fects model was chosen to analyze the data. Resultsshowed that YCWLP was not more effective than lip-id-lowering drugs in reducing LDL (MD = − 0.46;95% CI = [−1.21, 0.29]) (Figure 8).

Hemodynamic indexesTwo trials20,23 explored the effect on hemorheology by

testing the changes of some indexes after interventionbetween the treatment and control groups. Both stud-ies used three hemorheology indexes, namely, the highshear rate blood viscosity, low shear rate blood viscosi-ty, and the plasma viscosity. The three data groups oftwo trials all showed heterogeneity. After analyzing thedata with the random effects model, we found that YC-WLP was not more effective than the lipid-loweringdrugs in improving hemorheology (Figures 9-11).

Figure 6 Total triglyceride of Yinchenwuling power versus lipid-lowering drugs

Figure 7 High-density lipoprotein cholesterol of Yinchenwuling power versus lipid-lowering drugs

Figure 8 Low-density lipoprotein of Yinchenwuling power versus lipid-lowering drugs

Figure 9 High shear rate blood viscosity of Yinchenwuling power versus lipid-lowering drugs

Figure 10 Low shear rate blood viscosity of Yinchenwuling power versus lipid-lowering drugs

Figure 11 Plasma viscosity of Yinchenwuling power versus lipid-lowering drugs

141



Adverse eventsAdverse events were reported in three trials,20,21,24 whichinvolved 4 patients in the treatment group and 37 pa-tients in the control group. Three kinds of side effectswere observed. In the control group, 16 patients suf-fered from abnormally elevated alanine aminotransfer-ase levels and 4 patients had flushed skin or itching.Meanwhile, 4 patients in the treatment group and 17patients in the control group were reported to have ab-dominal pain, bloating, or constipation. The datashowed homogeneity (P = 0.71, I 2 = 0%), so the fixedeffect model was chosen for Meta-analysis. YCWLPhad a lower odds ratio of adverse events than the lip-id-lowering drugs [OR = − 0.08, 95% CI = (0.03,0.23)] (Figure 12).

DISCUSSIONSummary of the main findingsFive RCTs involving 363 patients were included in theMeta-analysis. The data and forest plots demonstratedthat YCWLP might be more effective at lowering lipidlevels than conventional drugs used to treat hyperlipid-emia. Based on the Meta-analysis, our preliminary con-clusion was that YCWLP had a significantly improvedclinical effective rate as compared with the controlgroup. YCWLP was more effective in lowering TC andTG and increasing HDL. However, YCWLP was notmore effective than the lipid-lowering drugs in reduc-ing LDL and improving hemorheology. Three trials re-ported side effects but showed that YCWLP has feweradverse events and may be potentially safer than lip-id-lowering drugs.

Strengths and limitationsThis is the first systematic review and Meta-analysisthat evaluates the efficacy and safety of YCWLP intreating hyperlipidemia. This study was conducted ac-cording to the PRISMA statement and followed a stan-dard protocol that was registered in PROSPERO (regis-tration number: CRD42015019428), an internationalprospective register of systematic reviews. All reviewersin this study have an academic qualification in Tradi-tional Chinese Medicine. The literature search compre-hensively and rigorously assessed the methodologicalquality of the included trials.This Meta-analysis has several limitations. The includ-ed trials were of poor methodological quality. Onlyone study reported a randomization procedure, where-

as the other four trials merely stated that the patientswere randomly divided into two groups. Given the lackof necessary information in the articles, we could notjudge whether randomization was properly conducted.All five studies lacked information on allocation con-cealment, as well as the blinding of participants, per-sonnel, and the outcome assessment. None of the stud-ies reported dropouts or loss to follow-up, and the in-tention-to-treat analysis and pre-trial sample size esti-mates were not mentioned. In addition, reporting onadverse events was inadequate. The information aboutquality control and qualitative testing for the herbalpreparations was lacking, which is a common problemin Chinese clinical trials. Given the insufficient num-ber of included trials in this Meta-analysis, we couldnot perform a funnel plot analysis. Therefore, potentialpublication bias may be present.In conclusion, the results of the included trials and Me-ta-analysis suggest that YCWLP may be more effectivethan lipid-lowering drugs in treating hyperlipidemia.However, the evidence available from this study is in-sufficient to draw a conclusion that confirms the bene-ficial effects of YCWLP on hyperlipidemia. Positivefindings should be conservatively interpreted becauseof the methodological limitations of the included trials.Additional well-designed clinical trials need to be con-ducted to verify the effectiveness and safety of YCWLPfor hyperlipidemia. Through the present Meta-analysis,we obtained some implications for future clinical stud-ies. Sample size estimation should be conducted beforeenrollment. Adequate information on methodologyshould also be provided, such as randomization, alloca-tion concealment, and blinding methods. The inten-tion to treat analysis and dropouts during the trialshould be clearly described. Follow-up should be takento assess the long-term effectiveness and safety of theintervention. More attention should be paid to the ad-verse events reporting. Furthermore, clinical trialsshould be registered in the WHO International Clini-cal Registry Platform in advance and should follow theCONSORT statement25 or CONSORT extension forHerbal Interventions.26 with detailed information ad-dressed.

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Figure 12 Adverse events from Yinchenwuling power versus lipid-lowering drugs

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Efficacy and safety of Yinchenwuling powder for ...ject word for hyperlipidemia as "Hyperlipidemias" and free texts as Hyperlipemia, Hyperlipemias, Hyperlipid-emia, Lipidemia, Lipidemias,