We systematically assess the current clinical evidence of Gualouxiebaibanxia (GLXBBX) decoction for the treatment of angina pectoris (AP). We included RCTs testing GLXBBX against conventional drugs and GLXBBX combined with conventional drugs versus conventional drugs. 19 RCTs involving 1730 patients were finally identified, and the methodological quality was evaluated as generally low. The results of the meta-analysis showed that GLXBBX alone had significant effect on improving angina symptoms (RR: 1.24, 95% CI 1.14 to 1.35;
Coronary artery disease (CAD) is one of the main causes of morbidity and mortality worldwide [
Angina significantly limits the ordinary activities of most of these patients and worsens their quality of life (QOL), in terms of not only physical activity/pain but also mental health [
Gualouxiebaibanxia (GLXBBX) decoction, which originated in the Eastern Han Dynasty (25–220), is a traditional Chinese medicinal herbal containing four commonly used herbs (
A systematic search was conducted in the following 7 online electronic databases from their inception until January 20, 2016: Cochrane Central Register of Controlled Trials (CENTRAL, 1996–2016), PubMed (1959–2016), EMBASE (1980–2016), Chinese Scientific Journal Database (VIP, 1989–2016), Chinese Biomedical Literature Database (1978–2016), Wanfang database (WMOD, 1985–2016), and Chinese National Knowledge Infrastructure (CNKI, 1979–2016). In addition, as GLXBBX is mainly prescribed in China, we also conducted a literature search of the website of the Chinese Clinical Trial Registry (available at
Studies that met the following criteria were included: (1) GLXBBX combined with conventional drugs versus conventional drugs; (2) GLXBBX versus conventional drugs; and (3) duration of treatment being at least 2 weeks. The participants who were suffering from and had been diagnosed with AP should be included regardless of the severity. The primary outcome measures in RCTs were mortality due to ischemic heart disease or incidence of heart events; the secondary outcome measure was reduction of angina symptoms (RAS) and ECG improvements. Other outcomes like frequency of angina attack (FAA), blood lipid, follow-up, and adverse events were also measured. Duplicated publications reporting the same groups of participants were excluded. The clinical standards of AP are by “the International Society and Federation of Cardiology/World Health Organization (ISFC/WHO) [
Two reviewers (Wei Liu and Xingjiang Xiong) independently screened the titles, abstracts, and key words of each searched article according to the eligibility criteria. One author (Xiaochen Yang) extracted data from the included RCTs and then put them into Microsoft Excel. Another 2 authors (Wei Liu and Fuyong Chu) examined the accuracy of extracted data. The data extraction form comprised the authors, title, publication year, sample size, age, sex distribution, diagnosis standard, study design, interventions in the treatment and control groups, composition of GLXBBX or modified GLXBBX, trial duration, outcome measures, and adverse effects. If there were discrepancies in the process of selection, whether to include or exclude a study was resolved by a third author (Hongxu Liu).
The methodological quality of trials was assessed independently by two authors (Xiaochen Yang and Xingjiang Xiong) using criteria from the Cochrane Handbook for Systematic Review of Interventions [
Meta-analyses of RCTs were performed by using RevMan 5.1 software (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, 2011). Dichotomous data were expressed as relative risk (RR) or continuous outcomes as weighted mean difference (WMD), both with 95% confidence intervals (CI). Subgroups analysis was conducted among different types of comparisons (including GLXBBX versus conventional drugs and GLXBBX plus conventional drugs versus conventional drugs). Heterogeneity between trials was recognized as significant when
An initial screening yielded 418 potentially relevant citations in accordance with the search strategy. A total of 176 articles were screened after 242 duplicates of the same articles included in different databases were removed. According to the inclusion criteria, 145 articles were excluded on the basis of the titles and abstracts. These studies were primarily excluded because they were not RCTs. A total of 37 full-text articles were retrieved for further assessment, of which 18 were excluded for the following reasons: participants not meeting the inclusion criteria (
Flow diagram of study selection and identification.
The 19 RCTs [
Characteristics and methodological quality of included studies.
Study ID | Sample (M/F) | Age (yrs) | Type of angina | Diagnosis standard | Intervention | Control | Course (week) | Outcome measure |
---|---|---|---|---|---|---|---|---|
Chen, 2008 [ |
60 |
T: 48–70 (52 ± 10) |
T: SAP: 20, UAP: 10 |
GCRNDTCM | Modified GLXBBX decoction |
Conventional drugs | 4 | RAS; ECG; adverse event |
|
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Bai and Shi, 2007 [ |
92 |
43–75 | AP | 1979 ISFC/WHO | Modified GLXBBX decoction |
Conventional drugs | 4 | RAS |
|
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Yang and Zhou, 2007 [ |
62 |
T: 48–75 |
AP | 1979 ISFC/WHO | Modified GLXBBX decoction |
Conventional drugs | 4 | RAS; ECG |
|
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Hu, 2001 [ |
69 |
T: 40–74 |
AP | 1979 ISFC/WHO | Modified GLXBBX decoction |
Conventional drugs | 4 | RAS; ECG |
|
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Zhang and Li, 2013 [ |
100 |
T: 35–72 (56.5 ± 5.3) |
SAP: 71; UAP: 29 | Unclear | Modified GLXBBX decoction |
Conventional drugs | 4 | RAS; ECG; BL |
|
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He et al., 2006 [ |
110 |
T: 47–76 (59.25 ± 6.07) |
AP | 1979 ISFC/WHO | Modified GLXBBX decoction |
Conventional drugs | 4 | RAS; ECG; BL; adverse event |
|
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Shi et al., 2013 [ |
90 |
T: 40–68 (53.75) |
AP | GCRNDTCM | Modified GLXBBX decoction |
Conventional drugs | 4 | RAS; ECG; adverse event |
|
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Si and Yin, 2012 [ |
60 |
T: 40–68 (53.75) |
UAP | Unclear | Modified GLXBBX decoction |
Conventional drugs | 2 | RAS; ECG |
|
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Wang, 2012 [ |
110 |
T: 39–75 (62.6) |
AP | GCRNDTCM | Modified GLXBBX decoction |
Conventional drugs | 2 | RAS; FAA; adverse event |
|
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Zhang and Zhu, 2003 [ |
120 |
T: 40–65 |
SAP | 1979 ISFC/WHO | Modified GLXBBX decoction |
Conventional drugs | 4 | RAS; ECG |
|
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Fang, 2011 [ |
64 |
T: 46–86 |
SAP | GCRNDTCM | Modified GLXBBX decoction |
Conventional drugs | 8 | RAS; BL |
|
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Zhu, 2012 [ |
80 |
T: 40–82 |
AP | 1979 ISFC/WHO | Modified GLXBBX decoction |
Conventional drugs | 8 | RAS |
|
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Li and Cai, 2011 [ |
82 |
T: 48–76 |
AP | 1979 ISFC/WHO | Modified GLXBBX decoction |
Conventional drugs | 4 | RAS |
|
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Zhang, 2015 [ |
84 |
T: 62–86 (71.53 ± 5.26) |
AP | GCRNDTCM | Modified GLXBBX decoction |
Conventional drugs | 2 | RAS; ECG |
|
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Ma, 2015 [ |
110 |
T: 40–81 (53.73 ± 5.6) |
T: SAP: 14, UAP: 41 |
1979 ISFC/WHO | Modified GLXBBX decoction |
Conventional drugs | 8 | RAS; ECG; adverse event |
|
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Yang et al., 2015 [ |
84 |
T: 55.9 ± 5.7 |
SAP: 30, UAP: 54 | 1979 ISFC/WHO | Modified GLXBBX decoction |
Conventional drugs | 2 | RAS; ECG |
|
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Tong and Xiong, 2013 [ |
63 |
T: 48–74 (61.77 ± 8.34) |
UAP | 2002 ACCF/AHA | Modified GLXBBX decoction |
Conventional drugs | 3 | RAS; BL; adverse event |
|
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Wang, 2015 [ |
210 |
T: 45–70 (59.25) |
SAP | 1979 ISFC/WHO | Modified GLXBBX decoction |
Conventional drugs | 4 | RAS; ECG; adverse event |
|
||||||||
Yang, 2015 [ |
80 |
T: 39–78 (58.3 ± 5.7) |
AP | GCRNDTCM | Modified GLXBBX decoction |
Conventional drugs | 8 | RAS; adverse event |
T, intervention group; C, control group; SAP: stable angina pectoris; UAP: unstable angina pectoris; RAS: reduction of angina symptoms; FAA: frequency of angina attack; GCRNDTCM: Guidelines of Clinical Research of New Drugs of Traditional Chinese Medicine; BL: blood lipid.
Compositions of GLXBBX decoction in the included trials.
Study ID | Formula | Composition of formula |
---|---|---|
Chen, 2008 [ |
Modified GLXBBX decoction | Snake Gourd Fruit (Gualou, |
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Bai and Shi, 2007 [ |
Modified GLXBBX decoction | Snake Gourd Fruit (Gualou, |
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Yang and Zhou, 2007 [ |
Modified GLXBBX decoction | Snake Gourd Fruit (Gualou, |
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Hu, 2001 [ |
Modified GLXBBX decoction | Snake Gourd Fruit (Gualou, |
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Zhang and Li, 2013 [ |
Modified GLXBBX decoction | Snake Gourd Fruit (Gualou, |
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He et al., 2006 [ |
Modified GLXBBX decoction | Snake Gourd Fruit (Gualou, |
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Shi et al., 2013 [ |
Modified GLXBBX decoction | Medicinal Changium Root (Shenqu, Medicated Leaven) 15 g, |
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Si and Yin, 2012 [ |
Modified GLXBBX decoction | Snake Gourd Fruit (Gualou, |
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Wang, 2012 [ |
Modified GLXBBX decoction | Snake Gourd Fruit (Gualou, |
|
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Zhang and Zhu, 2003 [ |
Modified GLXBBX decoction | Snake Gourd Fruit (Gualou, |
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Fang, 2011 [ |
Modified GLXBBX decoction | Snake Gourd Fruit (Gualou, |
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Zhu, 2012 [ |
Modified GLXBBX decoction |
|
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Li and Cai, 2011 [ |
Modified GLXBBX decoction | Snake Gourd Fruit (Gualou, |
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Zhang, 2015 [ |
Modified GLXBBX decoction | Snake Gourd Fruit (Gualou, |
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Ma, 2015 [ |
Modified GLXBBX decoction | Snake Gourd Fruit (Gualou, |
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Yang et al., 2015 [ |
Modified GLXBBX decoction | Snake Gourd Fruit (Gualou, |
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Tong and Xiong, 2013 [ |
Modified GLXBBX decoction | Snake Gourd Fruit (Gualou, |
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Wang, 2015 [ |
Modified GLXBBX decoction | Snake Gourd Fruit (Gualou, |
|
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Yang, 2015 [ |
Modified GLXBBX decoction | Snake Gourd Fruit (Gualou, |
Among trials, only 9 studies [
Risk of bias summary: reviewing authors’ judgments about each risk of bias item for each included study.
Risk of bias graph: reviewing authors’ judgments about each risk of bias item presented as percentages across all included studies.
There was no report of mortality as the primary outcome measures (e.g., AMI, severity arrhythmia, heart failure, and revascularization). We analyzed the outcomes, RAS (19 trials), ECG (13 trials), and blood lipid (HDL-C, LDL-C) level (4 trials), and used subgroup analysis with consideration of clinical heterogeneity across the studies. 19 studies were divided into two groups: one evaluated the effects of GLXBBX versus conventional drugs; the other compared GLXBBX plus conventional drugs versus conventional drugs alone.
All the 19 trials [
Analysis of RAS for AP. Forest plot of comparison: GLXBBX versus conventional drugs.
Analysis of RAS for AP. Forest plot of comparison: GLXBBX combined with conventional drugs versus conventional drugs.
13 RCTs evaluated the effect of ECG improvement [
Analysis of ECG improvement for AP. Forest plot of comparison: GLXBBX versus conventional drugs.
Analysis of ECG improvement for AP. Forest plot of comparison: GLXBBX combined with conventional drugs versus conventional drugs.
Compared with conventional medicine, one trial [
Forest plot of comparison: GLXBBX versus conventional drugs, outcome: HDL-C.
Compared with conventional drugs, 2 RCTs [
Compared with conventional medicine, two individual trials [
Three subgroups were analyzed based on methodological variables of different AP subtypes; 13 studies provided the data necessary to perform our evaluation. Of these RCTs, 2 RCTs [
The effect of GLXBBX for SAP or UAP group, outcome = RAS.
Study ID | Response rate% (response/ |
Therapeutic gain, % | NNT | RR | |
---|---|---|---|---|---|
Experimental | Control | ||||
Shi et al., 2013 [ |
93.33 (42/45) | 75.56 (34/45) | 17.77 | 5.63 | 1.24 |
Wang, 2012 [ |
94.12 (64/68) | 85.71 (36/42) | 8.41 | 11.89 | 1.10 |
Zhu, 2012 [ |
88.00 (44/50) | 66.67 (20/30) | 21.33 | 4.69 | 1.32 |
Li and Cai, 2011 [ |
95.24 (40/42) | 80.00 (32/40) | 15.24 | 6.56 | 1.19 |
Zhang, 2015 [ |
90.48 (38/42) | 71.43 (30/42) | 19.05 | 5.25 | 1.27 |
Ma, 2015 [ |
92.73 (51/55) | 76.36 (42/55) | 16.37 | 6.11 | 1.21 |
Yang et al., 2015 [ |
90.48 (38/42) | 80.95 (34/42) | 9.53 | 10.49 | 1.12 |
Yang, 2015 [ |
90.00 (36/40) | 72.50 (29/40) | 17.5 | 5.71 | 1.24 |
Pooled RR | 91.93 (353/384) | 76.49 (257/336) | 15.44 | 6.48 | 1.20 |
The effect of GLXBBX for SAP or UAP group, outcome = ECG.
Study ID | Response rate% (response/ |
Therapeutic gain, % | NNT | RR | |
---|---|---|---|---|---|
Experimental | Control | ||||
Shi et al., 2013 [ |
88.89 (40/45) | 71.11 (32/45) | 17.78 | 5.62 | 1.25 |
Zhang, 2015 [ |
73.81 (31/42) | 54.76 (23/42) | 19.05 | 5.25 | 1.35 |
Ma, 2015 [ |
96.36 (53/55) | 80.00 (44/55) | 16.36 | 6.11 | 1.20 |
Yang et al., 2015 [ |
88.10 (37/42) | 76.19 (32/42) | 11.90 | 8.40 | 1.16 |
Pooled RR | 87.5 (161/184) | 71.20 (131/184) | 16.30 | 6.13 | 1.23 |
The effect of GLXBBX for SAP, outcome = RAS.
Study ID | Response rate% (response/ |
Therapeutic gain, % | NNT | RR | |
---|---|---|---|---|---|
Experimental | Control | ||||
Zhang and Zhu, 2003 [ |
96.67 (58/60) | 86.67 (52/60) | 10.00 | 10.00 | 1.12 |
Fang, 2011 [ |
79.41 (27/34) | 66.67 (20/30) | 12.74 | 7.85 | 1.19 |
Wang, 2015 [ |
98.10 (103/105) | 88.57 (93/105) | 9.53 | 10.49 | 1.11 |
Pooled RR | 94.47 (188/199) | 84.62 (165/195) | 9.85 | 10.15 | 1.12 |
The effect of GLXBBX for SAP, outcome = ECG.
Study ID | Response rate% (response/ |
Therapeutic gain, % | NNT | RR | |
---|---|---|---|---|---|
Experimental | Control | ||||
Zhang and Zhu, 2003 [ |
71.67 (43/60) | 50.00 (30/60) | 21.67 | 4.61 | 1.43 |
Wang, 2015 [ |
97.14 (102/105) | 82.86 (87/105) | 14.28 | 7.01 | 1.17 |
Pooled RR | 87.88 (145/165) | 70.91 (117/165) | 16.98 | 5.89 | 1.24 |
The effect of GLXBBX for UAP, outcome = RAS.
Study ID | Response rate% (response/ |
Therapeutic gain, % | NNT | RR | |
---|---|---|---|---|---|
Experimental | Control | ||||
Si and Yin, 2012 [ |
93.33 (28/30) | 76.67 (23/30) | 16.66 | 6.00 | 1.22 |
Tong and Xiong, 2013 [ |
93.75 (30/32) | 87.10 (27/31) | 6.65 | 15.04 | 1.08 |
Pooled RR | 93.55 (58/62) | 81.97 (50/61) | 11.59 | 8.63 | 1.14 |
The effect of GLXBBX for UAP, outcome = ECG.
Study ID | Response rate% (response/ |
Therapeutic gain, % | NNT | RR | |
---|---|---|---|---|---|
Experimental | Control | ||||
Si and Yin, 2012 [ |
80.00 (24/30) | 63.33 (19/30) | 16.67 | 6.00 | 1.26 |
Pooled RR | 80.00 (24/30) | 63.33 (19/30) | 16.67 | 6.00 | 1.26 |
A total of 8 trials [
The forest plot of comparison of GLXBBX combined with conventional drugs and conventional drugs for the outcome of RAS was shown in Figure
Funnel plot of comparison: GLXBBX combined with conventional drugs versus conventional drugs for the outcome of RAS.
Angina pectoris (AP) is a highly prevalent condition in persons with known coronary artery disease (CAD), and the burden of cardiovascular (CV) disease (CVD) remains high, with more than 2200 Americans dying of CVD every day [
Nineteen claimed RCTs, with a total of 1730 patients with AP, met the inclusion criteria and were included in this review. The results suggested that RAS and ECG were significantly improved in patients receiving GLXBBX plus conventional drugs therapy or GLXBBX alone. The combination therapy of GLXBBX and conventional drugs could also reduce the frequency of angina attack. In recent years, there are many studies proving the role of lipid profile fractions for the development of coronary artery disease (CAD) [
Firstly, the following problems reported contribute to the limited methodological quality of most included trials. Although all studies claimed randomization, only 9 studies [
Secondly, heterogeneity is another critical issue that should be considered. The 4 independent trials [
Thirdly, none of the included trials reported severe adverse events possibly related to GLXBBX, and the adverse effects included 4 cases with nausea, 2.76% (4/145), 8 cases with gastrointestinal reaction, 4.57% (8/175), and 12 cases with headache, 10.43% (12/115), and these side effects may be related to the adverse effect of conventional drugs. Safety is a serious concern that should be recorded in detail. Thus, definitive conclusions about the safety of GLXBBX still cannot be drawn since 4 of 19 trials did report information on safety.
Fourthly, Figure
Last but not least, apart from the limitations on the mediocre methodological quality of included studies, the inadequate reporting of mortality or the incidence of complications was another important limitation of this systematic review. Moreover, outcome measures of AP including RAS and ECG improvement and the blood lipid level and frequency of angina attack were limited by relatively small sample size. As a result, evaluating the efficacy of GLXBBX on AP requires more strictly designed large-scale randomized clinical trials.
From this systematic review, we find that patients receiving GLXBBX adjunct therapy alone or combined with conventional drugs could significantly improve RAS, ECG, the blood lipid level, and frequency of angina attack in patient with AP. But the previous results should be read with caution owing to the poor methodological quality and some possible biases. Thereby, in order to explore the efficacy and safety of GLXBBX treating AP, well-designed, complete efficacy indicator, larger scaled, and multicenter randomized clinical trials with long-term follow-up are warranted for stronger evidence in the future.
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
All authors declare that they have no conflict of interests.
Wei Liu, Xingjiang Xiong, and Xiaochen Yang contributed equally to this paper.
The current work was partially supported by the National Natural Science Foundation of China (no. 81273741), Capital Clinical Medicine Application Characteristic Project of Beijing Science and Technology Committee (no. Z131107002213152), Scientific Research Common Program of Beijing Municipal Commission of Education (no. KM201311420084), and Basic Clinical Cooperation Projects of Capital Medical University (no. 13JL86).