Evidence-Based Complementary and Alternative Medicine

Evidence-Based Complementary and Alternative Medicine / 2012 / Article
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The Potential Benefit of Complementary/Alternative Medicine in Cardiovascular Diseases

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Review Article | Open Access

Volume 2012 |Article ID 636547 | https://doi.org/10.1155/2012/636547

Qinghua Shang, Zhaolan Liu, Keji Chen, Hao Xu, Jianping Liu, "A Systematic Review of Xuezhikang, an Extract from Red Yeast Rice, for Coronary Heart Disease Complicated by Dyslipidemia", Evidence-Based Complementary and Alternative Medicine, vol. 2012, Article ID 636547, 18 pages, 2012. https://doi.org/10.1155/2012/636547

A Systematic Review of Xuezhikang, an Extract from Red Yeast Rice, for Coronary Heart Disease Complicated by Dyslipidemia

Academic Editor: Myeong Soo Lee
Received14 Nov 2011
Accepted09 Jan 2012
Published12 Apr 2012

Abstract

Objective. This systematic review aims to evaluate the benefit and side effect of Xuezhikang for coronary heart disease (CHD) complicated by dyslipidemia. Methods. All randomized clinical trials (RCTs) with Xuezhikang as a treatment for CHD combined with dyslipidemia were considered for inclusion. Data extraction and analyses and quality assessment were conducted according to the Cochrane standards. Results. We included 22 randomized trials. Xuezhikang showed significant benefit on the incidence of all-cause deaths, CHD deaths, myocardial infarction, and revascularization as compared with placebo based on conventional treatment for CHD. It remarkably lowered total cholesterol (TC), triglyceride (TG), and low-density lipoprotein-cholesterol (LDL-C) as compared with the placebo or inositol nicotinate group, which was similar to statins group. Xuezhikang also raised high-density lipoprotein cholesterol (HDL-C) compared to placebo or no intervention, which was similar to Inositol nicotinate and slightly inferior to statins. The incidence of adverse events did not differ between the Xuezhikang and control group. Conclusions. Xuezhikang showed a comprehensive lipid-regulating effect and was safe and effective in reducing cardiovascular events in CHD patients complicated by dyslipidemia. However, more rigorous trials with high quality are needed to give high level of evidence.

1. Introduction

Coronary heart disease (CHD) is one of the most serious diseases with high incidence and mortality. Dyslipidemia contributes greatly to the formation and progression of atherosclerosis (AS), which plays a dominant role in leading to CHD. Patients with CHD are also commonly complicated with dyslipidemia. Modulating dyslipidemia actively, especially lowering low-density lipoprotein-cholesterol (LDL-C) by statins, has been demonstrated to be very crucial to prevent AS and reduce the morbidity and mortality of CHD. Most recently, the updated ESC/EAS guidelines for management of dyslipidemia [1] further highlighted the aggressive lipid-lowering strategy in subjects with documented coronary vascular disease (CVD) or previous myocardial infarction (MI). However, the application of statins might be restricted by the adverse effect on the liver function and creatine kinase, especially in patients with old age, multiple comorbid diseases, high-dose statins, or a combination lipid-lowering therapy. Thus it is of great clinical significance to find an effective but safer alternative therapy in CHD patients complicated by dyslipidemia.

Xuezhikang is a partially purified extract of fermented red yeast rice (Monascus purpureus). It is composed of 13 kinds of natural statins, unsaturated fatty acids, ergosterol, amino acids, flavonoids, alkaloid, trace element, and so forth. The health enhancing qualities of this yeast have been introduced and used in China for over two thousand years. At latest systematic review indicated the beneficial effects of Xuezhikang in the treatment of hyperlipidemia [2]. Therefore, Xuezhikang has been recommended in a guideline for China adult dyslipidemia prevention [3]. Recently, clinical benefits of Xuezhikang were also found in CHD patients combined with dyslipidemia in some randomized controlled trials [46]. This systematic review aims to evaluate the benefit and side effect of Xuezhikang, a potential alternative drug of statins, for CHD patients complicated by dyslipidemia, and thus provide further evidence for clinical application.

2. Methods

2.1. Inclusion Criteria

Randomized controlled trials (RCTs) comparing Xuezhikang with placebo, no intervention, or established lipid-lowing agents in English or Chinese were considered. Quasirandomized trials were excluded, and the duration of the intervention was no less than four weeks. Participants of all age with CHD complicated by dyslipidemia meeting with at least one of the current or past definitions or guidelines of CHD [including acute coronary syndrome (ACS)] [713] and dyslipidemia (treatment goal as the lower limit, see Table 1) [1420] were considered. Those who did not introduce diagnostic criteria in the text but stated patients with definite CHD or dyslipidemia were also included. Secondary dyslipidemia, high serum lipid level after meal, serious heart failure, and serious hepatic or renal failure were excluded.


OriginationDefinition of dyslipidemia or treatment goal of Patients with CHD or equivalents on serum lipid level

ATP I 1988 [14]Ideal lipid level: mmol/L (200 mg/dL); mmol/L (130 mg/dL). Patients with HDL- (35 mg/dL) were defined unmoral. The definition of dyslipidemia was according to the level of LDL-C

ATP II 1993 [15]Treatment goal: LDL- mmol/L (100 mg/dL)

Ministry of Health of the People’s Republic of China 1993 [8]The treatment goal was not introduced

CADPS 1997 [16]Treatment goal: mmol/L (180 mg/dL);  mmol/L (150 mg/dL); LDL-  mmol/L (100 mmol /L)

ATP III 2001 [17]Treatment goal: LDL-  mmol/L (100 mg/dL)

Implication of ATP III 2004 [18]Treatment goal: LDL-  mmol/L (100 mg/dL); the optional goal: LDL-  mmol/L (70 mg/dL)

AHA/ACC Guideline 2006 [19]Treatment goal: LDL-  mmol/L (100 mmol/L), and it is seasonal for lower than 1.8 mmol/L (70 mg/dL)

CADPG 2007 [3]Treatment goal:  mmol/L (160 mg/dL) and LDL-  mmol/L (100 mg/dL) for CHD or equivalents
Treatment goal:  mmol/L (120 mg/dL); LDL-  mmol/L (80 mg/dL) for ACS or ischemic cardiovascular disease complicated with diabetes mellitus
Suitable scope of HDL-C: 1.04 mmol/L (40 mg/dL); suitable scope of TG: <1.7 mmol/L (150 mg/dL)

ESC/EAS 2011 [1]In patients at very high CV risk (established CVD, type 2 diabetes, type I diabetes with target organ damage, moderate to severe CKD or a score ), the LDL-C goal is <1.8 mmol/L (70 mg/dL) and/or 50% LDL-C reduction when target level cannot be reached (I A recommendation)

Outcome measures include primary outcomes (including all-cause mortality, CHD mortality, incidence of MI, revascularization, and rehospitalization for unstable angina) and secondary outcomes [including serum total cholesterol (TC), triglyceride (TG), LDL-C, and-high density lipoprotein cholesterol (HDL-C)].

2.2. Search Strategy

Two reviewers searched the following databases up to September 2011 independently for the identifications of trials (publication or nonpublication): The Cochrane Library, Pubmed, Chinese Biomedical Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese VIP Information (VIP), and Wanfang Databases. We used the terms as follows: coronary heart disease, CHD, coronary artery disease, angina pectoris, myocardial infarction, acute coronary syndrome, cardi*, and Xuezhikang, red yeast rice, monascus. Because of different characteristics of various databases, MeSH terms and free text terms were used regardless of the report types in full text, title, keyword, subject terms, or abstract.

2.3. Data Extraction and Quality Assessment

Two reviewers (Shang QH, Liu ZL) independently extracted data according to a data extraction form made by the authors. Disagreements were resolved by consensus or consultation from a third reviewer (Liu JP). The methodological quality of trials was assessed independently using criteria from the Cochrane Handbook for Systematic Review of Interventions, Version 5.0.1 (Shang QH, Liu ZL) [20]. We contacted with the authors if there was any doubt in randomization and blinding method. The items included 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), and other bias. We judged each item from three levels (“Yes” for a low of bias, “No” for a high risk of bias, “Unclear” otherwise), and then we assessed the trials and categorized them into three levels: low risk of bias (all the items were in low risk of bias), high risk of bias (at least one item was in high risk of bias), unclear risk of bias (at least one item was in unclear).

2.4. Data Synthesis

We used Revman 5.1 software provided by the Cochrane Collaboration for data analyses. Studies were stratified by the types of comparisons. We will express dichotomous data as risk ratio (RR) and its 95% confidence intervals (CI). Continuous outcome will be presented as mean difference (MD) and its 95% CI. Heterogeneity was recognized significant when %. Fixed effects model was used if there is no significant heterogeneity of the data; random effects model was used if significant heterogeneity existed ( ). Publication bias was explored using a funnel plot.

3. Results

3.1. Description of Included Trials

22 RCTs (23 papers) [46, 2139] were included, 21 papers were published in Chinese, one paper published in English, and one was unpublished as a postgraduate dissertation. The whole process of trials selection was demonstrated in Figure 1. The characteristics of included trials were listed in Table 2.


IDDiagnostic criteria of CHD (ACS)Diagnostic criteria of dyslipidemiaTypes of CHDSample size (I/C)Age (y, I/C)Interventions groupControl groupDuration of treatmentOutcomes evaluationBalance
report
of
baseline

CCSPS 2005
[4]
Not specifiedTC: 4.40–6.47MI2441/2429(Male: ;
female: )
/(male: ;
female: 6
Xuezhikang 600 mg  therapy (no detail)Placebo + conventional therapy (no detail)4 year
in average
Serum lipid level (TC, TG, LDL-C, HDL-C), all-cause mortality, cardiovascular events, serum lipid level (TC, TG, HDL-C, LDL-C),
ADs
Yes

Dai et al. 1999 [5]WHO 1979 and Gao 1994Ministry of Health of the People’s Republic of China 1993Unstable angina33/25 Xuezhikang 600 mg, Nitrate esters 10 mg BID + nifedipine GIFTS 30 mg QD/diltiazem 30 mg tid + metoprolol 12.5 mg BID + aspirin 50 mg QD8 weeksSerum lipid level (TC, TG, HDL-C, LDL-C), ADsYes

Gao and Liao 2003 [21]Not specified  mmol/L,
LDL-  mmol/L,
 mmol/L
Stable Angina30/3053–85, 67.5 in averageXuezhikang 600 mg  therapy (no detail)Fluvastatin (Lescol see fluvastatin) 20 mg QD + conventional therapy (no detail)4 weeksSerum lipid level (TC, TG, LDL-C, HDL-C)Unclear

Guan 2010
[22]
Not specified  mmol/L;
; LDL- ;
.
Two items of the above were included
Stable Angina72/6449–76, 62 in
average
Xuezhikang 600 mg BIDSimvastatin 10 mg QN1 yearCHD mortality, ADsYes

Huang et al. 2005 [23]WHO 1979CADPS 1997OMI and UA45/6344–72Xuezhikang 600 mg BIDSimvastatin 20 mg QN6 weeksSerum lipid level (TC, TG, LDL-C, HDL-C)Yes

Huang et al. 2009 [24]WHO 1979CADPS 1997Unclear Xuezhikang 600 mg, Nitroglycerine 20 mg BIDIV + 10% KCL + insulinIV QD12 weeksSerum lipid level (TC, TG, HDL-C, LDL-C)Yes

Jiang and Cai 2001 [25]Not specifiedCADPS 1997Unclear Xuezhikang 600 mg  therapy (as same as B)Simvastatin 10 mg QN + conventional therapy (nitrate esters 10 mg tid, aspirin 100 mg QD or anticoagulation drugs or thrombolytic drug or hypoglycemic)8 weeksSerum lipid level (TC, TG, LDL-C, HDL-C), ADsYes

Li et al. 2011 [26]References [12, 13]As same as Guan 2010Unclear
Xuezhikang 600 mg BIDLovastatin 40 mg QD (20 mg QD if the ALT or AST was 3 times higher than the normal)8 weeksSerum lipid level (TC, TG, LDL-C, HDL-C), ADsYes

Lin et al. 2009 [27]Chinese Society of cardiology 2000  mmol/L
or LDL-  mmol/L
Unstable angina 35–71, 55.4 in averageXuezhikang 600 mg, Simvastatin 60 mg QN + conventional therapy (nitrate esters, β adrenergic blocking agent, CCB, aspirin, low molecular heparin and et al.6 monthsSerum lipid level (TC, LDL-C), CHD eventsYes

Lou et al. 2008 [28]Chinese society of cardiology 2000  mmol/L
and  mmol/L
and LDL-
Unstable angina Xuezhikang 600 mg  therapy (as same as B)Simvastatin 20 mg QD + conventional therapy (anticoagulation drugs, nitrate esters, β adrenergic blocking agent, ACEI, CCB and et al.)6 monthsSerum lipid level (TC, TG, LDL-C, HDL-C), Cardiovascular events, ADsUnclear

Ma and Teng 2005 [29]WHO 1979CADPS 1997Unclear
Xuezhikang 600 mg  Conventional therapy (nitrate esters, adrenergic blocking agent, ACEI, CCB and et al.)8 weeksSerum lipid level (TC, TG)Yes

Qi et al. 2001 [30]WHO 1979  mmol/LUnclear Xuezhikang 600 mg, BID (600 mg TID if the lipid level was still higher than the treatment goal) + controlConventional therapy (nitrate esters, adrenergic blocking agent, ACEI, CCB, and et al.)12 weeksSerum lipid level (TC, TG), ADsUnclear

Shang 2007
[31]
WHO 1979CADPS 1997Stable Angina Xuezhikang 1200 mg therapy (as same as control group)Atorvastatin 10 mg QN + conventional therapy (aspirin, nitrate esters, β adrenergic blocking agent, ACEI, and et al.)2 monthsSerum lipid level (TC, TG, LDL-C, HDL-C)Yes

Wang and Xiao 2000 [32]WHO 1979CADPS 1997MI, UA, CHD with no symptoms 49–76, 62 in averageXuezhikang 600 mg  50 mg QDInositol niacinate 400 mg TID + aspirin 50 mg QD1 yearSerum lipid level (TC, TG, LDL-C, HDL-C), cardiovascular evnets, ADsYes

Wang et al.
2004 [6]
ACC/AHH 2000CADPS 1997ACS
Xuezhikang 600 mg  Conventional therapy (aspirin, nitrate esters, β adrenergic blocking agent, ACEI, and et al.)12 weeksSerum lipid level (TC, TG, LDL-C, HDL-C), ADsYes

Xu 2005 [39]Chinese Society of cardiology 2000Not specifiedUA UnclearXuezhikang 600 mg group (1)(1) Conventional therapy (isosorbide dinitrate 10 mg tid, betaloc 25–50 mg BID/TID, aspirin 50–150 mg QD, low molecular heparin 0.4–0.6 mL Q12H or diltiazem 30 mgtid/qid, or plendil 5 mg QD/BID or captopril 12.5–25 mg TID or nitroglycerine)
(2) Conventional therapy (as same as (1)) and atorvastatin 20 mg Qn
1 monthSerum lipid level (TC, TG, LDL-C, HDL-C)Yes

Yan 2006 [34]Chinese Society of cardiology 2000LDL-C: 1.84–4.12 mmol/LUA Xuezhikang 600 mg  magnesium polarizing liquorIV + heparinIH + Aspirin, Nitrate esters, β adrenergic blocking agent CCB and et al.8 weeksSerum lipid level (TC, TG, LDL-C, HDL-C), ADsUnclear

Yan and Li
2007 [33]
WHO 1979CADPS 1997Unclear
Xuezhikang 600 mg, Nitroglycerine 20 mg BID.iv + 10% KCL + insulinIV QD8 weeksSerum lipid level (TC, TG, LDL-C, HDL-C)Yes

Yu et al. 2002 [35]WHO 1979CADPS 1997Unclear
Xuezhikang 600 mg, therapy (as same as control)Placebo + conventional therapy (aspirin, nitrate esters, CCB and et al.)8 weeksSerum lipid level (TC, TG, LDL-C, HDL-C)Yes

Zhang 2010
[36]
Reference [8]CADPS 1997Unclear (58–80, 72.3 in average)
/(59–82, 73.1 in average)
Xuezhikang 600 mg, Fluvastatin 40 mg QD4 weeksSerum lipid level (TC, TG, LDL-C, HDL-C)Yes

Zhang 2011
[37]
Unclear  mmol/L
or LDL-  mmol/L
complicated with high TG level
Unclear40/40
Xuezhikang 300 mg TIDAtorvastatin 20 mg/d QD8 weeksSerum lipid level (TC, TG, LDL-C), ADsYes

Zhou et al.
2003 [38]
Unclear  mmol/L and (or) LDL-  mmol/L or complicate with >1.92 mmol/LACS Xuezhikang 600 mg Conventional therapy (nitrate esters, β adrenergic blocking agent, CCB, anticoagulation drugs, thrombolytic drug, PTCA and et al.)8 weeksSerum lipid level (TC, TG, LDL-C)Yes

6520 Participants were included (3264 in intervention group and 3256 in control group). Two of the trials did not report the gender, and 4905 male and 1538 female were included in the other 20 trials. A total of 7 criteria of CHD (including ACS) were selected, but 6 trials did not introduce criteria of CHD but mentioned “patients with CHD were eligible to include.” 3 criteria of dyslipidemia were used for 11 trials, and the other 11 trials only reported the serum lipid levels, which were categorized to dyslipidemia according to the previous and current definitions and guidelines Table 1. One trial [4] included patients with MI; five of the trials [5, 27, 28, 34, 39] included patients with unstable angina; two of the trials [6, 38] included patients with ACS; three of the trials [21, 22, 31] included patients with stable angina. The other 11 trials [2326, 29, 30, 32, 33, 3537] did not introduce the types of CHD or all types were included.

Patients in 19 trials prescribed Xuezhikang 600 mg QD (regulation was conducted for adverse events), one trial used Xuezhikang 600 mg TID if the serum TC or TG still higher after having been prescribed for 6 weeks (600 mg BID in previous 6 weeks) [30], one trial [37] prescribed Xuezhikang 300 mg TID, and one trial [31] prescribed Xuezhikang 1200 mg QN. The duration of treatment ranged from 4 weeks to 7 years.

There were five comparisons in the review according to various control groups. (1) Xuezhikang and conventional therapy versus conventional therapy (8 trials) [5, 6, 24, 29, 33, 34, 38, 39]; (2) Xuezhikang and conventional therapy versus placebo and conventional therapy (2 trials) [4, 35]; (3) Xuezhikang and conventional therapy versus statin and conventional therapy (9 trials) [2123, 25, 26, 28, 31, 37, 39]; (4) Xuezhikang and statin and conventional therapy versus statin and conventional therapy (2 trials) [27, 36]; (5) Xuezhikang and aspirin versus inositol nicotinate and aspirin (1 trials) [32]. One trial [39] was designed as three groups with two comparisons and Xuezhikang and conventional therapy versus conventional therapy; Xuezhikang and conventional therapy versus atorvastatin and conventional therapy.

3.2. Methodological Quality of Included Trials

According to the criteria introduced above, no trial was evaluated as having a low risk of bias. Only one trial of the 22 trials reported the method to generate the allocation sequence (random number table) in the paper [6]. After we contacted with the authors, six trials announced a correct method for allocation sequence [46, 31, 33, 35]. One trial was assessed as having adequate concealment [35]. Two trials applied double-blinding [4, 35], and two trials used single-blinding but did give us objective to be blinded [25, 37]. One trial blinded the outcome assessors [4]. One trial reported prior sample size estimation and mentioned intention-to-treat analysis [4]. Five trials reported information on withdrawal/dropout [4, 6, 22, 29, 32]. 18 trials [46, 2227, 29, 3133, 3539] provided baseline data for the comparability among groups. The results of the assessment of risk of bias are presented in a “risk of bias summary” figure produced by Revman 5.1 automatically Figure 2.

3.3. Effect Estimates of Outcomes (Tables 3 and 4)

Outcomes (comparisons)Treatment group (n/N)Control group (n/N)RR95% CI

(1) All-cause mortality
Xuezhikang capsule and conventional therapy versus placebo and conventional therapy
CCSPS 2005 [4]126/2429189/24410.67
(2) Mortality of CHD
(2.1) Xuezhikang capsule and conventional therapy versus placebo and conventional therapy
CCSPS 2005 [4] 134/24410.69
(2.2) Xuezhikang and conventional therapy versus simvastatin and conventional therapy
Guan 2010 [22] 6/640.15
Lou et al. 2008 [28] 1/410.95
Overall (FEM, I2 = 13%) 0.26
(2.3) Xuezhikang and simvastatin and conventional therapy versus simvastatin and conventional therapy
Lin et al. 2009 [27] 0.33
(2.4) Xuezhikang and aspirin versus inositol nicotinate and aspirin
Wang and Xiao 2000 [32] 0.15
(3) Myocardial infarction
(3.1) Xuezhikang and conventional therapy versus placebo and conventional therapy
CCSPS 2005 [4] 0.39
(3.2) Xuezhikang and conventional therapy versus simvastatin and conventional therapy
Lou et al. 2008 [28] 0.95
(3.3) Xuezhikang and simvastatin and conventional therapy versus simvastatin and conventional therapy
Lin et al. 2009 [27] 0.2
(4) Revascularization
(4.1) Xuezhikang capsule and conventional therapy versus placebo and conventional therapy
CCSPS 2005 [4] 0.67
(4.2) Xuezhikang and conventional therapy versus simvastatin and conventional therapy
Lou et al. 2008 [28] 1.14
(5) Rehospitalization
(5.1) Xuezhikang and conventional therapy versus simvastatin and conventional therapy
Lou et al 2008 [28] 1.02
(5.2) Xuezhikang and simvastatin and conventional therapy versus simvastatin and conventional therapy
Lin et al. 2009 [27] 0.2


Serum lipid level (comparison)Intervention groupControl groupWeight (%) MD 95% CI
MeanSDMeanSD

(1) TC (mmol/L)
(1.1) Xuezhikang and conventional therapy versus conventional therapy
Dai et al. 1999 [5] 5.41 0.87 6.54 0.89 11.40 −1.13
Huang et al. 2009 [24] 4.98 0.79 5.99 0.87 13.30 −1.01
Ma and Teng 2005 [29] 9.00
Wang et al. 2004 [6] 4.33 0.96 0.79 11.10 −1.97
Xu 2005 [39] 5.49 1.12 0.93 6.60 −0.71
Yan 2006 [34] 17.30
Yan and Li 2007 [33] 0.13 5.93 0.23 17.00 −1.03
Zhou et al. 2003 [38] 0.54 4.84 0.78 14.30 −0.54
Overall (REM, I2 = 92%)100
(1.2) Xuezhikang and conventional therapy versus placebo and conventional therapy
CCSPS 2005 [4] 4.65 0.67 5.22 0.88 −0.57
Yu et al. 2002 [35] 0.58 6.72 0.85 −2.62
(1.3) Xuezhikang and conventional therapy versus statin and conventional therapy
(1.3.1) Xuezhikang and conventional therapy versus lovastatin and conventional therapy
Li et al. 2011 [26] 4.57 1.42 5.32 1.72 9.5 −0.75
(1.3.2) Xuezhikang and conventional therapy versus simvastatin and conventional therapy
Huang et al. 2005 [23] 4.62 0.63 4.36 13.8 0.26
Jiang and Cai 2001 [25] 5.19 4.91 0.66 12.8 0.28
Lou et al. 2008 [28] 5.4 0.12 0.11 14.4
SubgroupOverall (REM, I2 = 69%)
(1.3.3) Xuezhikang and conventional therapy versus fluvastatin and conventional therapy
Gao and Liao 2003 [21] 4.05 0.74 3.63 0.59 13.1 0.42
(1.3.4) Xuezhikang and conventional therapy versus atorvastatin and conventional therapy
Shang 2007 [31] 4.65 0.79 4.88 0.85 13.5 −0.23
Xu 2005 [39] 5.49 1.12 0.92 8.8 −0.01
Zhang 2011 [37] 4.51 0.38 3.35 14.1 1.16
SubgroupOverall (REM, I2 = 97%)
After sensitive analysisSubgroupOverall (FEM, I2 = 0%)
TotalOverall (REM, I2 = 96%)
After sensitive analysisTotalOverall (REM, I2 = 66%)
(1.4) Xuezhikang and statin and conventional therapy versus statin and conventional therapy
(1.4.1) Xuezhikang and simvastatin and conventional therapy versus simvastatin and conventional therapy
Lin et al. 2009 [27] 0.71 0.81 35.6
(1.4.2) Xuezhikang and fluvastatin and conventional therapy versus fluvastatin and conventional therapy
Zhang 2010 [36] 0.24 64.4
TotalOverall (REM, I2 = 68%)
(1.5) Xuezhikang and aspirin versus inositol nicotinate and aspirin
Wang and Xiao 2000 [32] −1.05
2. TG (mmol/L)
(2.1) Xuezhikang and conventional therapy versus conventional therapy
Dai et al. 1999 [5] 1.84 0.68 0.87 5.50 −0.48
Huang et al. 2009 [24] 1.49 0.31 1.97 0.37 44.40 −0.48
Ma and Teng 2005 [29] 10.50
Wang et al. 2004 [6] 1.88 0.5 2.2 0.76 7.70 −0.32
Xu 2005 [39] 0.92 2.52 1.67 0.90 0.18
Yan and Li 2007 [33] 1.54 2.02 0.59 19.10 −0.48
Zhou et al. 2003 [38] 0.66 0.61 12.10
Overall (FEM, I2 = 0%)100%
(2.2) Xuezhikang and conventional therapy versus placebo and conventional therapy
CCSPS 2005 [4] 1.58 0.78 1.75 0.88 50.80 −0.17
Yu et al. 2002 [35] 2.22 0.71 3.51 0.36 49.20 −1.29
(2.3) Xuezhikang and conventional therapy versus statin and conventional therapy
(2.3.1) Xuezhikang and conventional therapy versus lovastatin and conventional therapy
Li et al. 2011 [26] 3.75 1.17 3.82 1.29 1.3 −0.07
(2.3.2) Xuezhikang and conventional therapy versus simvastatin and conventional therapy
Huang et al. 2005 [23] 1.85 0.81 1.92 0.72 5.5 −0.07
Jiang and Cai 2001 [25] 1.9 0.72 2.11 0.91 3.5 −0.21
Lou et al. 2008 [28] 3.1 0.2 3.2 0.33 35.2
SubgroupOverall (FEM, I2 = 0%)
(2.3.3) Xuezhikang and conventional therapy versus fluvastatin and conventional therapy
Gao and Liao 2003 [21] 1.01 0.63 1.42 0.46 6.2 −0.41
(2.3.4) Xuezhikang and conventional therapy versus atorvastatin and conventional therapy
Shang 2007 [31] 1.61 0.53 1.57 0.55 14.1 0.04
Xu 2005 [39] 2.7 0.92 2.22 0.73 1.0 0.48
Zhang 2011 [37] 1.64 0.33 1.61 0.21 33.0 0.03
SubgroupOverall (FEM, I2 = 0%)
TotalOverall (FEM, I2 = 45%)
(2.4) Xuezhikang and statin and conventional therapy versus statin and conventional therapy
Zhang 2010 [36] 1.58 1.85 −0.27
(2.5) Xuezhikang and aspirin versus inositol nicotinate and aspirin
Wang and Xiao 2000 [32]
(3) LDL-C (mmol/L)
(3.1) Xuezhikang and conventional therapy versus conventional therapy
Dai et al. 1999 [5] 3.42 0.96 3.93 0.81 13.50 −0.51
Huang et al. 2009 [24] 2.88 0.91 3.96 0.96 14.10 −1.08
Wang et al. 2004 [6] 2.21 0.4 3.87 0.56 15.20 −1.66
Xu 2005 [39] 2.82 0.95 3.7 0.95 10.50 −0.88
Yan 2006 [34] 2.89 0.44 2.9 0.6 15.50 −0.01
Yan and Li 2007 [33] 2.97 3.88 16.20 −0.91
Zhou et al. 2003 [38] 3.22 0.6 3.68 0.71 15.00 −0.46
Overall (REM, I2 = 94%)
(3.2) Xuezhikang and conventional therapy versus placebo and conventional therapy
CCSPS 2005 [4] 2.66 0.85 3.23 0.85 50.30 −0.57
Yu et al. 2002 [35] 2.48 0.39 0.39 49.70 −1.82
(3.3) Xuezhikang and conventional therapy versus statin and conventional therapy
(3.3.1) Xuezhikang and conventional therapy versus lovastatin and conventional therapy
Li et al. 2011 [26] 2.45 0.72 3.25 0.84 10.6
(3.3.2) Xuezhikang and conventional therapy versus simvastatin and conventional therapy
Huang et al. 2005 [23] 2.68 0.55 2.52 0.49 13.9 0.16
Jiang and Cai 2001 [25] 3.1 0.41 12.2
Lou et al. 2008 [28] 2.8 0.09 2.9 0.1 15.7
SubtotalOverall (REM, I2 = 79%)
(3.3.3) Xuezhikang and conventional therapy versus fluvastatin and conventional therapy
Gao and Liao 2003 [21] 2.13 0.58 2.08 0.61 12.2 0.05
(3.3.4) Xuezhikang and conventional therapy versus atorvastatin and conventional therapy
Shang 2007 [31] 2.54 0.56 2.44 0.52 14.2
Xu 2005 [39] 2.82 0.95 2.93 0.52 6.9 −0.11
Zhang 2011 [37] 3.04 0.48 2.51 0.32 14.3 0.53
SubtotalOverall (REM, = 84%)
After sensitive analysisSubtotalOverall (FEM, = 0%)
TotalOverall (REM, = 90%)
After sensitive analysisTotalOverall (REM, = 64%)
(3.4) Xuezhikang and statin and conventional therapy versus statin and conventional therapy
(3.4.1) Xuezhikang and simvastatin and conventional therapy versus simvastatin and conventional therapy
Lin et al. 2009 [27] 0.78 8.4
(3.4.2) Xuezhikang and fluvastatin and conventional therapy versus fluvastatin and conventional therapy
Zhang 2010 [36] 2.87 0.32 91.6 −0.43
TotalOverall (FEM, = 0%)
(3.5) Xuezhikang and aspirin versus inositol nicotinate and aspirin
Wang and Xiao 2000 [32] 100 −0.88
(4) HDL-C (mmol/L)
(4.1) Xuezhikang and conventional therapy versus conventional therapy
Dai et al. 1999 [5] 1.71 0.42 1.04 0.49 14.60 0.67
Huang et al. 2009 [24] 1.12 0.3 0.82 0.2 19.50 0.3
Wang et al. 2004 [6] 1.44 0.38 1.31 0.27 17.00 0.13
Xu 2005 [39] 1.67 0.51 1.68 0.75 7.10 −0.01
Yan 2006 [34] 1.04 1.04 20.60
Yan and Li 2007 [33] 1.09 0.09 0.07 21.10 0.29
Overall (REM, = 93%)
(4.2) Xuezhikang and conventional therapy versus placebo and conventional therapy
CCSPS 2005 [4] 1.24 0.31 1.19 0.31 50.80 0.05
Yu et al. 2002 [35] 1.45 0.25 0.97 0.19 49.20 0.48
(4.3) Xuezhikang and conventional therapy versus statin and conventional therapy
(4.3.1) Xuezhikang and conventional therapy versus lovastatin and conventional therapy
Li et al. 2011 [26] 1.12 0.38 1.06 0.36 11.4 0.16
(4.3.2) Xuezhikang and conventional therapy versus simvastatin and conventional therapy
Huang et al. 2005 [23] 1.85 0.81 1.92 0.72 6.4 −0.09
Jiang and Cai 2001 [25] 1.16 0.17 1.21 0.12 19.0 −0.05
Lou et al. 2008 [28] 0.8 0.03 0.9 0.03 21.4
Overall (FEM, = 0%)
(4.3.3) Xuezhikang and conventional therapy versus fluvastatin and conventional therapy
Gao and Liao 2003 [21] 1.14 0.27 0.45 11 −0.16
(4.3.4) Xuezhikang and conventional therapy versus atorvastatin and conventional therapy
Shang 2007 [31] 1.45 0.41 1.44 0.33 14.9 0.01
Xu 2005 [39] 1.67 0.51 1.53 0.48 3.8 0.14
Zhang 2011 [37] 1.09 0.48 1.62 0.27 12.1 −0.53
SubtotalOverall (REM, = 93%)
After sensitive analysisSubtotalOverall (FEM, I2 = 0%)
TotalOverall (REM, I2 = 79%)
After sensitive analysisTotalOverall (FEM, I2 = 35%)
(4.4) Xuezhikang and fluvastatin and conventional therapy versus fluvastatin and conventional therapy
Zhang 2010 [36] 0.97 0.28 0.82 0.06 100 0.15
(4.5) Xuezhikang and aspirin versus inositol nicotinate and aspirin
Wang and Xiao 2000 [32] 0.95 0.22 0.91 0.25 100 0.17

Note: FEM: fixed effects model; REM: random effects model.
3.3.1. All-Cause Mortality

There was only 1 trial [4] reported the all-cause mortality in the comparisons of Xuezhikang and conventional therapy versus placebo and conventional therapy [RR 0.67; 95% CI 0.54 to 0.83; 1 trial, ].

3.3.2. Mortality of CHD

There were 5 studies [4, 22, 27, 28, 32] that presented the effect of Xuezhikang in reducing the mortality of CHD. Compared to placebo on the basis of conventional therapy, Xuezhikang showed a reduction of mortality of CHD (RR 0.69; 95% CI 0.54 to 0.89; 1 trial, ) [4]. Compared to simvastatin on the basis of conventional therapy, Xuezhikang showed no significant difference in mortality of CHD (RR 0.26; 95% CI 0.06 to 1.21; 2 trial, ) [22, 28]. Compared to no treatment on the basis of simvastatin and conventional therapy, Xuezhikang showed no effect in reducing mortality of CHD (RR 0.33; 95% CI 0.01 to 7.80; 1 trial, ) [27]. Compared with inositol nicotinate on the basis of aspirin, Xuezhikang showed no significant difference in mortality of CHD (RR 0.15; 95% CI 0.02 to 1.18; 1 trial, ) [32].

3.3.3. Incidence of MI

There were 3 studies reporting CHD events in 3 different comparisons. Compared with placebo on the basis of conventional therapy, Xuezhikang showed a reduction of morbidity of MI (RR 0.39; 95% CI 0.28 to 0.55; 1 trial, ) [4]. Compared with simvastatin on the basis of conventional therapy, Xuezhikang showed no significant difference (RR 0.95; 95% CI 0.30 to 3.05; 1 trial, ) [28]. In comparisons of Xuezhikang and simvastatin and conventional therapy versus simvastatin and conventional therapy, Xuezhikang showed no effect in reducing incidence of MI (RR 0.20; 95% CI 0.01 to 3.96; 1 trial, ) [27].

3.3.4. Revascularization

Revascularization included percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG). There were 2 studies [4, 28] reporting revascularization in 2 different comparisons. Compared with placebo on the basis of conventional therapy, Xuezhikang showed a significant reduction of revascularization (RR 0.67; 95% CI 0.50 to 0.89; 1 trial, ) [4]. Compared with simvastatin on the basis of conventional therapy, Xuezhikang showed no significant difference (RR 1.14; 95% CI 0.38 to 3.46; 1 trial, ) [28].

3.3.5. Rehospitalization for Unstable Angina

There were 2 trials [27, 28] reporting rehospitalization in 2 different comparisons. Compared with simvastatin on the basis of conventional therapy, Xuezhikang showed no significant difference in the number of rehospitalization (RR 1.02; 95% CI 0.57 to 1.84; 1 trial, ) [28]. Compared with no treatment on the basis of simvastatin and conventional therapy, Xuezhikang showed no effect in reducing rehospitalization (RR 0.20; 95% CI 0.03 to 1.59; 1 trial, ) [27].

3.3.6. Serum TC Level

There were 21 studies that reported the level of total cholesterol Table 4, but one trial only reported the serum lipid level of the treatment group [30]. (1) Compared to no treatment with cointervent