Please wait a minute...
6TMR Modern Herbal Medicine  2019, Vol. 2 Issue (2): 91-114    DOI: 10.12032/TMRmhm2017B42
Review     
Wenxin granule for cardiac arrhythmia: an overview of systematic reviews
Ruijin Qiu1#, Changming Zhong1#, Huichan Yuan1, Xiaoyi Tang2, Ya Huang1, Tianmai He1, Songjie Han1, Manke Guan1, Min Li1, Jiayuan Hu1, Xiaoyu Zhang1, Jing Chen3,*(), Hongcai Shang1,4,*()
1Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
2The First Hospital of Tsinghua University, Beijing, China.
3Baokang Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.
4School of Medical Information Engineering, Guangzhou University of Chinese medicine. Guangzhou, China.
Download: HTML     PDF(1104KB)
Export: BibTeX | EndNote (RIS)      

Objectives: Evaluating the quality of systematic reviews/meta-analysis of Wenxin granule in treating cardiac arrhythmia to provide evidence for clinical practice, and analyzing the problems in the research to identify potential research priorities for researchers. Method: The systematic reviews of Wenxin granule in treating cardiac arrhythmia were searched from 8 databases. The methodological quality and evidence quality were assessed by AMSTAR and GRADE respectively. Results: Nineteen eligible systematic reviews with 52,905 participants were included. The overall scores of AMSTAR ranged from 3 to 10 with a mean score of 6.5, the median score was 6. There were 9 (9/19, 47.37%) systematic reviews had the score of 7 or more. 6 of them with appropriate information were assessed the quality of evidence by GRADE. The results showed that the overall quality of evidence was limited (range from “very low” to “low”), no “moderate” or “high” quality of evidence existed. For the outcome reporting, no systematic reviews reported endpoints and limited evidence showed that there is causality between Wenxin granule and adverse effects/events. The outcome matrix showed that there are obvious heterogeneity and incompleteness for the outcome reporting in included systematic reviews, so that some included studies cannot be conducted meta-analysis. Meanwhile, there were studies excluded because of inappropriate outcome measures, such as outcome measures did not meet inclusion criteria, treatment time did not meet inclusion criteria, treatment time was unclear, incomplete data or the data cannot be extracted. Conclusions: Wenxin granule have limited efficacy and safety for treating arrhythmia. In the future, high quality of RCTs and systematic reviews should be conducted. Core outcome set for cardiac arrhythmia is needed to improve outcome reporting and decrease waste.

Highlights
1. This is the first overview of systematic reviews for Wenxin granule in treating cardiac arrhythmia, which summarized the efficacy and safety of Wenxin granule in treating cardiac arrhythmia and strictly assessed the quality of methodology and evidence.
2. Besides methodological quality and evidence quality assessment, this overview also analyzed some other problems, such as outcome reporting in systematic reviews and RCTs, so that researchers may identify potential research priorities from the results.
3. The outcome matrix of included reviews showed that there was heterogeneity in outcome reporting, and some clinical trials cannot be included in systematic reviews or cannot be conducted meta-analysis in systematic reviews because of inappropriate outcomes reporting. These problems reduce the value of clinical trials and systematic reviews. This research presents that core outcome set for cardiac arrhythmia is necessary to solve these problems.



Key wordsWenxin granule      cardiac arrhythmia      overview of systematic reviews     
Published: 25 April 2019
Fund:  This work wasfunded byNational Natural Science Foundation of China [No: 81430098].
Corresponding Authors: Chen Jing,Shang Hongcai     E-mail: cjshcsyc@126.com;shanghongcai@foxmail.com
About author: # These authors contributed equally to this work.
Cite this article:

Ruijin Qiu, Changming Zhong, Huichan Yuan, Xiaoyi Tang, Ya Huang, Tianmai He, Songjie Han, Manke Guan, Min Li, Jiayuan Hu, Xiaoyu Zhang, Jing Chen, Hongcai Shang. Wenxin granule for cardiac arrhythmia: an overview of systematic reviews. 6TMR Modern Herbal Medicine, 2019, 2(2): 91-114. doi: 10.12032/TMRmhm2017B42

URL:

https://www.tmrjournals.com/mhm/EN/10.12032/TMRmhm2017B42     OR     https://www.tmrjournals.com/mhm/EN/Y2019/V2/I2/91

Databases Search strategies
PubMed #1(((Wenxin[Title/Abstract]) OR Wen xin[Title/Abstract]) OR wenxinkeli[Title/Abstract]) OR WXKL[Title/Abstract]
#2 (systematic review[Title/Abstract]) OR meta[Title/Abstract]
#3 #1 AND #2
Cochrane Library


Web of Science
wenxin:ti,ab,kw or wen xin:ti,ab,kw or wenxinkeli:ti,ab,kw or WXKL:ti,ab,kw
Notes: search in ‘Cochrane Reviews’ and ‘Other Reviews’

#1 TS=(Wenxin OR Wen xin OR wenxinkeli OR WXKL)
#2 TS=(systematic review OR meta)
#3 #1 AND #2
Embase #1 'wenxin':ti,ab,kw OR 'wen xin':ti,ab,kw OR 'wenxinkeli':ti,ab,kw OR 'wxkl':ti,ab,kw
#2 'systematic review':ti,ab,kw OR 'meta':ti,ab,kw
#3 #1 AND #2
Table 1 Full search strategies of English electronic databases
Figure 1 The flowchart of the overview of systematic reviews
Study ID Conditions No. of authors No. of Trials/ participants Quality of original trials AMSTAR score Comparisons Outcomes and included trials/participants Conclusions
Chen 2013 [17] PAF 13 14/1180 High or unclear (Cochrane handbook) 9 WG vs WM, WG + WM vs WG 1. P-wave dispersion (Pd, 9 /828)
2. maintenance of SR (7/ 476)
After treatment with WG, there is a significant reduction in Pd in patients with PAF, and the maintenance of SR is significantly improved. Due to the poor quality of design and methodology, the evidence remains weak.
Du 2014 [33] AF 2 13/1050 1 (Jadad scale, 0-5) 4 WG + CT vs CT 1. Clinical efficacy (13/1050)
2. SR conversion rate (3/263)
3. ventricular rate (4/319)
4. adverse effect (6/558)
Compared with CT, WG can further improve the clinical outcome, reduce ventricular rate, increase conversion rate and reduce the incidence of adverse reactions in the treatment of atrial fibrillation.
Zhao 2014 [34] AF 5 11/805 High (Cochrane handbook) 7 Metoprolol + WG vsmetoprolol 1. Symptoms (4/269)
2. Attacks of AF (5/330)
3. Adverse effect (9/657)
Compared to metoprolol, WG + metoprololhas better effect on symptoms and attacks of AF. The adverse effect rate between two groups is not significantly different.But because of small sample, low quality and high risk of bias of included trials, much more researchers are needed.
Wang 2015 [35] AF 3 12/924 Range 3-4, (Revised Jadad scale, 0-7) 5 WG + amiodaronevsamiodarone 1. Clinical efficacy (11/854)
2. Adverse effects (8/630)
WG + amiodaronehas significant curative effect and less adverse reactions with higher safety. As this analysis has limited quantity of RCTs, more large-sample RCT with higher quality are required.
Wang C 2017 [20] AF 9 15/1447 High risk of bias (Cochrane handbook) 9 WG vsamiodarone; WG + amiodaronevsamiodarone 1. The SR maintenance rate (WG group: 6/528, WG + amiodarone group: 12/1136)
2. The total incidence of adverse drug (WG group: 6/528, WG + amiodarone group: 10 RCTs)
WG may have a potential effect on less adverse events in SR control for patients with AF. WG+ amiodarone can significantly increase the rate of SR maintenance and reduce the incidence of adverse events compared to amiodarone. However, there were some methodological defects in the included studies.
Li M 2018 [36] AF 15 24/2246 Unclear (Cochrane handbook) 6 WG + CT vs CT/ placebo; WG + WM vs WM 1. Mean ventricular rate (10/870)
2. Frequency of AF (2 trials)
3. Duration of AF (1 trial)
4. SR conversion time (5/407)
5. SR conversion rate (6/499)
6. Recurrence rate of AF (5/346)
7. Heart functional outcome (7 trials)
8. ECG (6 trials)
9.Adverse effect (10/1012)
Compared with WM, WG combined with WM could effectively control rapid ventricular rate, reduce the frequency and duration of AF, shorten SR conversion time, increase SR conversion rate, reduce AF recurrence rate, improve cardiac structural and electrophysiological dysfunction with less adverse reactions. However, due to the low quality of the included trials, the evidence is weak.
Du 2014 [37] VPB 2 20/1985 1 (Jadad scale, 0-5) 5 WG + CT vs CT 1. ECG (8/714)
2. Clinical efficacy (20/1985)
3. Adverse effect (11/1117)
WG can significantly improve the clinical efficacy and ECG, reduce the adverse reaction ,but which needs to be further confirmed by more large-sample, high-quality RCTs.
He 2016 [18] VPB 5 10/2251 Moderate or high risk of bias (Cochrane handbook) 10 WG vs placebo/ CT, WG + WM vs WM 1. VPB’s numbers (10/2168)
2. Symptoms (9/1976)
3. Adverse events (8/1998)
In spite of poor methodology quality of most included trials, the results show that WG, alone or combined with WM, might be beneficial to reduce VPBs’ numbers and relieve symptoms for non-fatal VPBs patients. WG may be associated with an increased risk of gastrointestinal adverse events and a reduced risk of proarrhythmic reactions.
Guo 2016 [38] VPB 6 20/1568 Range 1-3 (Revised Jadad scale, 0-7) 7 WG + metoprolol + CT vsmetoprolol + CT 1. Smptoms (10/703)
2. Efficacy of Bradyarrhythmia (19/1476)
3. Adverse events (13/952)
WG + metoprolol can effectively improve the symptoms of patients, and significantly diminish the ventricular premature, while there is no significant difference in the incidence of total adverse drug reactions and bradycardia between the two groups. Also the difference in the incidence of atrioventricular block is with marginal significance. So the safety between the two groups may need further study after more samples be tested.
Shen J 2016 [39] VPB 9 10/938 Range 1-3 (Revised Jadad scale, 0-7) 6 WG + metoprololvsmetoprolol 1. Clinical efficacy (4/503)
2. Symptoms (7/658)
3. Dynamic ECG (6/ 435)
4. Adverse effect (8/696)
WG + metoprololtakes more curative effect than metoprolol alone, also can relieve symptoms and improve ECG, and has no significant difference in adverse reactions. The quantity and quality of included trials are limited. RCTs with higher quality for further proving the conclusion.
Li M 2017 [19] VPB with HF 8 8/595 High risk of bias (Cochrane handbook) 8 based on CT, WG alone or WG + WM vs blank control or WM 1. The frequency of VPBs within 24 h (4/332)
2. LVEF (6/475)
3. BNP (4 RCTs)
4. VPBs (6/511)
5. LVED ( 12 weeks: 2/147, 8 weeks: 3/220 )
6. 6-min walking test (2/147)
7. Adverse effects (8/595)
WG may be effective and safe for treating VPBs and HF. However, these problems (blind uncertainty, single country) were main limitations and deficiencies, resulting in the lack of high quality evidence.
Lu J 2018 [40] ventricular arrhythmia 4 31/3075 Range 2-3 (Revised Jadad scale, 0-7) 5 WG + metoprolol + CT vsmetoprolol + CT 1. Clinical efficacy (31/3075)
2. 24 h dynamic ECG (11/1124)
3.ST segment depression (6/671)
4. Duration of ST segment depression (7/751)
5. Number of VPBs (7/751)
6.Short-term ventricular tachycardia (5/478)
7. Adverse effect (16/1857)
Compared with metoprolol alone, WG + metoprolol can significantly improve the total clinical efficacy, reduce the ST segment depression, shorten the ST segment depression duration, and reduce the number of VPBs and s Short-term ventricular tachycardia. In addition, they can reduce adverse reactions rate. However, the disease status, drug dose, and follow-up time of included studies were not completely unified, and the quality of the included studies was low, which affected the reliability of the results.
Miao 2016
[41]
APB 4 16/1441 High or unclear (Cochrane handbook) 6 WG + WM/CT vsWM/CT; WG vs WM/CT 1. Clinical efficacy (13 trials)
2. Symptoms (2 trials)
3. ECG (3 trials)
WG alone or combined with WM can be more effective in improving the ECG and clinical symptoms in patients with atrial premature contractions. However, the low quality of the included studies caused a bad effect on the conclusion which still need high quality studies to demonstrate.
Li 2011 [23] Arrhythmias 6 24/25640 Moderate or high risk (Cochrane handbook) 7 WG vsmexiletine/ propafenone/amiodarone 1. Clinical efficacy (WG vsmexiletine: 4/472, WG vspropafenone: 15/1677, WG vsamiodarone: 5/415)
2. ECG (WG vsmexiletine: 2/205, WG vspropafenone: 10/1281, WG vsamiodarone: 2/171)
3. Gastrointestinal adverse reaction (WG vspropafenone: 10/915, WG vsamiodarone: 4/383)
4. Adverse effect rate (WG vspropafenone: 7/673 WG vsamiodarone: 4/383)
The effect of WG in anti-arrhythmia is not worse than the WM, and the incidence of adverse reactions is lower. The study was limited by the quality of included studies.
Shi 2012
[42]
Arrhythmias 2 10/987 Moderate or high risk (Cochrane handbook) 3 WG vs WM 1. Clinical efficacy (10/987) The comprehensive analysis shows that WG is a safe and effective drug for arrhythmia.
He 2014
[43]
Arrhythmias 3 25/2947 Moderate risk of bias (Cochrane handbook) 6 WG vs WM 1. Clinical efficacy (WG vspropafenone: 9/1129, WG vsmetoprolol: 5/490, WG vsmexiletine hydrochloride: 3/412, WG vsamiodarone: 8/916)
2. ECG (WG vspropafenone: 7/895, WG vs metoprolol:3/318)
3. Adverse effect (6/726)
WG is effective and safe for arrhythmia, but more clinical study should be done to confirm the effective and safety.
Shi 2017 [22] Arrhythmias 6 7/683 Moderate or high risk of bias (Cochrane handbook) 7 Bisoprolol + WG vsbisoprolol 1. Arrhythmias (7/683)
2. Symptoms (7/683)
3. Adverse effect (6/576)
The results showed to a certain extent that combined treatment of WG and bisoprolol is more effective and can reduce the adverse reactions in treating CHD-induced arrhythmias.
Zhang J 2017 [44] Arrhythmias 4 23/2671 Range 1-2 (Jadad scale) 5 WG + amiodaronevsamiodarone 1. Clinical efficacy (21/2082)
2. ECG (2/256)
3. Number of VPBs (3/365)
4. Number of APBs (2/179)
5. Time of symptom relief (2/118)
6. Adverse effect (16/1462)
WG + amiodaroneis more effective and safe for the treatment of CHD arrhythmia than amiodarone alone.
Liang Y 2017 [21] Heart failure with arrhythmia 2 5/472 High risk of bias (Cochrane handbook) 8 WG + amiodarone + CT vsamiodarone + CT 1. LVEF (4/386)
2. QTduration (5/472)
3. Heart rate (5/472)
4. Clinical efficacy (4/386)
5. Adverse effect (4/372)
WG + WM had more effect on the treatment of heart failure combined with arrhythmia. High quality of RCTs are needed to support this conclusion.
Table 2 Characteristics of included systematic reviews/meta-analyses
Study ID Conditions No. of trials P-wave dispersion Maintenance of SR Clinical efficacy SR conversion rate Ventricular rate Adverse effect Symptoms Attacks of AF Frequency of AF Duration of AF SR conversion time Recurrence rate of AF Heart functional outcome ECG
Chen 2013 [17] PAF 14 9 (64.29%) 7(50.00%)
Du 2014 [33] AF 13 13(100%) 3(23.08%) 4(30.77%) 6(46.15%)
Zhao 2014 [34] AF 11 9(81.82%) 4(36.36%) 5(45.45%)
Wang 2015 [35] AF 12 11(91.67%) 8(66.67%)
Wang C 2017 [20] AF 15 15(100%) 13(86.67%)
Li M 2018 [36] AF 24 6(25.00%) 10(41.67%) 10(41.67%) 2(8.33%) 1(4.17%) 5(20.83%) 5(20.83%) 7(29.17%) 6(25.00%)
Table 3 The outcome matrix of included reviews for atrial fibrillation
Study ID Conditions No. of trials Clinical efficacy Adverse effect Symptoms Dynamic ECG ECG TCM syndrome VPB’s numbers Bradyarrhythmia The frequency of VPBs within 24 h LVEF BNP VPBs LVED 6-min walking test
Du 2014 [37] VPB 20 20(100%) 11(55.00%) 8(40.00%)
He 2016 [18] VPB 10 8(80.00%) 9(90.00%) 10(100%)
Guo 2016 [38] VPB 20 13(65.00%) 10(50.00%) 19(95.00%)
Shen J 2016 [39] VPB 10 4(40.00%) 8(80.00%) 7(70.00%) 6(60.00%)
Li M 2017
[19]
VPB with HF 8 8(100%) 4(50.00%) 6(75.00%) 4(50.00%) 6(75.00%) 5(62.50%) 2(25.00%)
Table 4 The outcome matrix of included reviews for ventricular premature beats
Study ID Conditions No. of trials LVEF ST segment depression Clinical efficacy Number of APBs Number of VPBs Gastrointestinal adverse reaction Adverse effect Symptoms Duration of ST segment depression Short-term ventricular tachycardia Arrhythmias Time of symptom relief Heart rate QT duration Dynamic ECG ECG
Lu J 2018 [40] ventricular arrhythmia 31 6(19.35%) 31(100%) 7(22.58%) 16(51.61%) 7(22.58%) 5(19.35%) 11(35.48%)
Miao 2016 [41] APB 16 13(81.25%) 2(12.5%) 3(18.75%)
Li 2011 [23] Arrhythmias 24 24(100%) 14(58.33%) 14(58.33%) 14(58.33%)
Shi 2012 [42] Arrhythmias 10 10(100%)
He 2014 [43] Arrhythmias 25 25(100%) 6(24.00%) 10(40.00%)
Shi 2017 [22] Arrhythmias 7 7(100%) 7(100%) 7(100%)
Zhang J 2017 [44] Arrhythmias 23 21(91.30%) 2(8.70%) 3(13.04%) 16(69.57%) 2(8.70%) 2(8.70%)
Liang Y 2017 [21] Heart failure with arrhythmia 5 4(80%) 4(80.00%) 4(80%) 5(100%) 5(100%)
Table 5 The outcome matrix of included reviews for other types of arrhythmia
Study ID Adverse effects/events Relationship between AEs and WG
Du 2014 [33] 6 RCTs (6/13, 46.15%) mentioned AEs. The rate of AEs is lower in WG + CT group than CT group (OR=0.52, 95%CI: 0.29-0.94, P=0.03) Not reported
Zhao 2014 [34] 9 RCTs (9/11, 81.82%) mentioned AEs. In WG + metoprolol group, 25 patients had AEs, included dizziness, nausea and loss of appetite (n=24), improved T4 (n=1). In metoprolol group, 23 patients had AEs, included fatigue (n=1), abdominal distension (n=1), improved T4 (n=2), dizziness, nausea and loss of appetite (n=15), atrioventricular block (n=6), drug discontinuance because of heart failure (n=1). There is no statistical significance between two groups for AEs (RR=1.00, 95% CI: 0.59-1.69, P=1.00) Not reported
Wang 2015 [35] 8 RCTs (8/12, 66.67%) mentioned AEs. The rate of AEs is lower in WG + amiodarone group than amiodarone group (RR=0.46, 95%CI: 0.32-0.65, P<0.0001). Not reported
Wang C 2017 [20] 6 RCTs (6/12, 50%) mentioned AEs in WG and amiodaronecomparision. In amiodarone group, the AEs included cardiac toxic reaction such as sinus bradycardia (n=8), Q-T interval prolongation (n=2), II AVB (n=1), and other organ toxic reaction, for instance stomach discomfort (n=16), thyroid dysfunction (n=7), pulmonary fibrosis (n=2), liver dysfunction (n=1). In WG group, the AEs included stomach discomfort, dizziness and sinus bradycardic (n=20). There were 2 patients dropped out of the trials in the amiodarone group for the adverse events of pulmonary fibrosis.The total incidence of adverse drug events was lower in the WG group than in amiodarone group (RR=0.54, 95% CI: 0.32, 0.90, P=0.02).
10 RCTs (10/12, 83.33%) mentioned AEs both in the combination with WXG and amiodarone group and amiodarone group. The combination with WXG and amiodarone do not increase the incidence of adverse events in the treatment duration when compared with amiodarone. (RR= 0.51, 95%, CI: 0.32,0.80, P=0.003)
Not reported
Li M 2018 [36] 10 (10/2441.67%) RCTs mentioned AEs. In WG group, there were 45 (45/508, 8.86%) patients had AEs, while there were 84 (84/504, 16.67%) in control group. AEs included thyroid dysfunction, gastrointestinal discomfort, bradycardia, QT interval prolonged. Not reported
Du 2014 [37] 11 (11/20, 55.00%) RCTs mentioned AEs. WG group had less AEs than control group (OR=0.27, 95%CI: 0.19-0.39). Not reported
He 2016 [18] 8 (8/10, 80.00%) RCTs mentioned AEs. In WG group, AEs included gastrointestinal adverse reactions (n=19). While in control group, AEs included dizziness, hypotension, first degree AV, or a sinus bradycardia (n=22). There was no statistical difference between WG group and control group in the rate of total adverse drug events (RR=0.59, 95%CI: 0.35-1.01, P = 0.05). Not reported
Guo 2016 [38] 13 (13/20, 65.00%) RCTs mentioned AEs. The rate of AEs in WG group was 10.25% (49/478), while it was 14.56% (69/474) in control group. In WG group, the AEs included nausea (n=14), upper abdominal discomfort (n=10), bradycardia (n=10), gastrointestinal reaction (n=9), fatigue (n=5), hypotension (n=1). In control group, the AEs included nausea (n=20), upper abdominal discomfort (n=2), bradycardia (n=19), gastrointestinal reaction (n=12), fatigue (n=4), hypotension (n=4), atrioventricular block (n=8). The WG group had less rate of AEs ([RR=0.70, 95% CI: 0.50-0.98, P=0.04) than control group. Not reported
Shen J 2016 [39] 8 (8/10, 80.00%) RCTs mentioned AEs. There was no statistical difference between WG group and control group in the rate of AEs (RR=0.77, 95%CI: 0.42-1.18, P=0.18). Not reported
Li M 2017
[19]
All of the RCTs (8/8, 100%) reported adverse drug reactions. In the treatment group, AEs included bradycardia (n=8), dizziness (n=6) and nausea (n=5). In the control group, AEs included, including bradycardia, low cardiac function, thyroid dysfunction, gastrointestinal reaction, dizziness, etc (n= 16). Not reported
Lu J 2018 [40] 16 (16/31, 51.61%) RCTs reported AEs. WG group had less AEs than control group. (OR=0.56, 95%CI: 0.40-0.77, P=0.0005). Not reported
Li 2011 [23] 14 (14/24, 58.33%) RCTs reported gastrointestinal reaction. WG group can lower gastrointestinal reaction than propafenone (OR= 0.24, 95% CI: 0.12 -0.45, P <0.01). There was no statistical difference between WG andamiodarone (OR=0.58, 95% CI: 0.28-1.22, P> 0.05).The total incidence of gastrointestinal reactions in WG group was significantly lower than control group (OR = 0.34, 95% CI: 0.21- 0.54, .P < 0.01). 11 (11/24, 45.83%) RCTs reported AE of arrhythmia. WG group can lower arrhythmia than propafenone (OR=0.15, 95% CI: 0.05-0.47, P <0.01) and amiodarone (OR=0. 06, 95% CI: 0.01-0.24, P<0.01).The total incidence of gastrointestinal reactions in WG group was significantly lower than control group (OR= 0.10, 95% CI: 0.04-0.23, P<0.01). Yes
He 2014
[43]
6(6/25, 24.00%) RCTs reported gastrointestinal reaction. WG group can lower gastrointestinal reaction than amiodarone (OR=0.54, 95% CI: 0.29-0.98, P=0.04). 6(6/25, 24.00%) RCTs reported AE of arrhythmia. WG group can lower arrhythmia than amiodarone (OR=0.05, 95% CI: 0.02-0.16, P<0.00001). Yes
Shi 2017 [22] All of RCTs mentioned AEs (7/7, 100%) AEs, which included dizziness, nausea, loss of appetite, thirst, bradycardia, hypotension, gastrointestinal reaction. WG group had less AEs than control group (RR= 0. 41, 95% CI: 0.22-0.77, p<0.01) Not reported
Zhang J 2017 [44] 16 (16/23, 69.57%) RCTs mentioned AEs. WG + amiodarone had less AEs than amiodarone (OR=0.68, 95%CI: 0.49. 0.94, P=0.02). Not reported
Liang Y 2017 [21] 4 (4/5, 80%) RCTs mentioned AEs. In treatment group, 6 (6/186, 3.23%) patients had AEs, including gastrointestinal reaction (n=4), sinus bradycardia (n=1), abnormal liver function (n=1). In control group, 22 (22/186, 11.83%) patients had AEs, including gastrointestinal reaction (n=15), sinus bradycardia (n=5), abnormal liver function (n=2). Not reported
Table 6 Reported adverse effects/events in included reviews
Stud ID Item 1 Item 2 Item 3 Item 4 Item 5 Item 6 Item 7 Item 8 Item 9 Item 10 Item 11 Score
Chen 2013[17] No Yes Yes Yes No Yes Yes Yes Yes Yes Yes 9
Du 2014 [33] No Yes No No No No Yes No Yes Yes No 4
Zhao 2014 [35] No Yes Yes Can’t answer No Yes Yes Yes Yes Yes No 7
Wang 2015 [35] No No No No No Yes Yes Yes Yes Yes No 5
Wang C 2017 [20] No Yes Yes Yes No Yes Yes Yes Yes Yes Yes 9
Li M 2018 [36] No Yes Yes Can’t answer No Yes Yes Yes No Yes No 6
Du 2014 [37] No Yes No No No No Yes Yes Yes Yes No 5
He 2016[18] Yes Yes Yes Yes No Yes Yes Yes Yes Yes Yes 10
Guo 2016 [38] No Yes Yes Can’t answer No Yes Yes Yes Yes Yes No 7
Shen J 2016 [39] No No Yes No No Yes Yes Yes Yes Yes No 6
Li M 2017 [19] No Yes Yes Can’t answer No Yes Yes Yes Yes Yes Yes 8
Lu J 2018 [40] No Yes Yes Can’t answer No No Yes No Can’t answer Yes Yes 5
Miao 2016 [41] No Yes Yes Can’t answer No Yes Yes Yes Yes No No 6
Li 2011 [23] No Yes Yes Can’t answer No Yes Yes Yes Yes Yes No 7
Shi 2012 [42] No No No Can’t answer No Yes Yes No No Yes No 3
He 2014 [43] No Yes Yes Can’t answer No Yes Yes Yes Yes No No 6
Shi 2017 [22] No Yes Yes Can’t answer No Yes Yes Yes Yes Yes No 7
Zhang J 2017 [44] No Yes Yes No No No Yes No Yes Yes No 5
Liang Y 2017 [21] No Yes Yes Yes No Yes Yes Yes Yes Yes No 8
Table 7 The methodological quality assessment of included systematic reviews with AMSTAR
Item Yes, n (%) No, n (%) Can’t answer, n (%) Not applicable, n (%)
1. Was an ‘a priori’ design provided? 1 (5.26) 18 (94.74) 0 0
2. Was there duplicate study selection and data extraction? 16 (84.21) 3 (15.79) 0 0
3. Was a comprehensive literature search performed? 15 (78.95) 4 (21.05) 0 0
4. Was the status of publication (i.e., grey literature) used as an inclusion criterion? 4 (21.05) 5 (26.32) 10 (52.63) 0
5. Was a list of studies (included and excluded) provided? 0 19 (100) 0 0
6. Were the characteristics of the included studies provided? 15 (78.95) 4 (21.05) 0 0
7. Was the scientific quality of the included studies assessed and documented? 19 (100) 0 0 0
8. Was the scientific quality of the included studies used appropriately in formulating conclusions? 15 (78.95) 4 (21.05) 0 0
9. Were the methods used to combine the findings of studies appropriate? 16 (84.21) 2 (10.53) 1 (5.26) 0
10. Was the likelihood of publication bias assessed? 17(89.47) 2 (10.53) 0 0
11. Was the conflict of interest stated? 5 (26.32) 14 (73.68) 0 0
Table 8 Methodological quality assessment of included systematic reviews (n=19)
Publication time Number of publications AMSTAR score Mean AMSTAR score
2011 1 7 7
2012 1 3 3
2013 2 2-9 5.5
2014 4 4-7 5.5
2015 1 5 5
2016 4 6-10 7.25
2017 5 5-9 7.4
2018 1 5 5
Table 9 The relationship of publication time with AMSTAR score
Study ID Conditions No. of studies No. of patients Effect Quality
Treatment group Control group Relative (95% CI) Absolute
Chen 2013 [17] PAF WG or WG + WM WM
P-Wave Dispersion
9 420 408 - MD < 7.65 (11.73 to 3.56 lower) Low
SR maintainance
7 203/240 (84.6%) 148/236 (62.7%) RR 1.35 (1.21 to 1.51) >219/1000 (> 132 to >320) Very low
Zhao 2014[34] AF Metoprolol + WG Metoprolol
Symptoms
4 117/134 (87.3%) 88/135 (65.2%) RR 1.34 (1.17 to 1.54) >222/1000 (>111 to >352 ) Very low
Attacks of AF
5 141/165 (85.5%) 108/165 (65.5%) RR 1.31 (1.15 to 1.48) >203/1000 (>98 to >314 ) Very low
Attacks of AF
6 239/257 (93%) 165/218 (75.7%) RR 1.23 (1.14 to 1.34) >174/1000 (>106 to >257 ) Very low
Wang C[20] AF SR maintainance
6 WG group Amiodarone group RR 0.91 (0.75 to 1.09) <41/1000 (< 114 to > 41 ) Very low
112/269 (41.6%) 118/259 (45.6%)
12 WG + amiodarone group Amiodarone group RR 1.34 (1.22 to 1.47) >169/1000 (>110 to >234 ) Low
383/572 (67%) 281/564 (49.8%)
Adverse effects
6 WG group Amiodarone group RR 0.52 (0.31 to 0.87) <69/1000 (<19 to <99 ) Very low
20/269 (7.4%) 37/259 (14.3%)
10 WG + amiodarone group Amiodarone group RR 0.51 (0.32 to 0.8) <53/1000 (<21to <73 ) Very low
26/480 (5.4%) 51/475 (10.7%)
He M, 2016 [18] VPB WG or WG + WM Placebo / CT / WM
VPB's numbers
10 940/1134 (82.9%) 646/1034 (62.5%) RR 1.16 (1 to 1.35) >100/1000 (> 0 to >219 ) Very low
Symptoms
9 20/1044 (1.9%) 31/954 (3.2%) RR 0.59 (0.35 to 1.01) <13/1000 (<21 to >0 ) Very low
Adverse effects
8 20/1044 (1.9%) 31/954 (3.2%) RR 0.59 (0.35 to 1.01) <13/1000 (<21 to >0 ) Very low
Guo 2016[38] VPB WG + metoprolol metoprolol
Smptoms
10 317/356 (89%) 246/347 (70.9%) RR 1.26 (1.17 to 1.36) >184/1000 (> 121 to >255 ) Low
Efficacy of Bradyarrhythmia
19 660/741 (89.1%) 536/735 (72.9%) RR 1.22 (1.16 to 1.29) >160/1000 (>117 to >211 ) Low
Adverse events
13 49/478 (10.3%) 69/474 (14.6%) RR 0.7 (0.5 to 0.98) <44/1000 (<3 to <73) Very low
Li M 2017[19] VPB with HF The frequency of VPBs
2 WG + WM Blank control or WM - <337.92 (366.94 to <308.91) Very low
106 102
2 WG Blank control - < 1001.14 (1257.65 to <744.63) Very low
62 62
4 WG or WG+βblockers β blockers or blank control - <427.08 (526.73 to< 327.43) Very low
168 164
WG or WG+β blocker β blockers or blank control
LVEF
6 239 236 - > 4.12 (2.97 to >5.27) Very low
The effect of VPBs
6 37/257 (14.4%) 75/254 (29.5%) RR 0.48 (0.34 to 0.69) <154/1000 (<92 to <195 ) Very low
The variation of LVED
5 183 184 - <0.61 (<1.41 to>0.18) Very low
Table 10 The quality of evidence for included reviews
Study ID Outcome measures did not meet inclusion criteria Treatment time did not meet inclusion criteria Treatment time was unclear Incomplete data or the data cannot be extracted
He 2016 [18] 8/174 Not reported Not reported 1/11
Chen 2013 [17] 86/209 Not reported Not reported Not reported
Li 2011 [23] Unclear Unclear Unclear Unclear
Wang 2015 [35] Unclear Not reported Not reported 1/26
Shi 2017 [22] 27/36 Not reported Not reported Not reported
Zhao 2014[34] Unclear Unclear Unclear 2/13
Guo2016[38] Unclear Unclear Unclear Unclear
Miao 2016 [41] Unclear Unclear Unclear Unclear
Du 2014 [37] Unclear Unclear Unclear Unclear
Du 2014 [33] Unclear Unclear Unclear Unclear
He 2014 [43] Unclear Unclear Unclear Unclear
Shi 2012 [42] Unclear Unclear Unclear Unclear
Wang C [20] 69/216 9/33 1/33 Not reported
Li M 2017 [19] 28/46 Not reported Not reported Not reported
Zhang J 2017 [44] Unclear Unclear Unclear Unclear
Liang Y 2017 [21] 8/19 Not reported Not reported 3/19
Shen J 2016 [39] 2/12 Not reported Not reported Not reported
Lu J 2018 [40] Not reported Not reported Not reported Not reported
Li M 2018 [36] 86/184 3/184 10/184 Not reported
Table 11 Excluded studies because of inappropriate outcome measures
1.   Y. Miyasaka, M. E. Barnes, B. J. Gersh, et al. Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence.Circ 2006, 114: 119-125
doi: 10.1161/CIRCULATIONAHA.105.595140
2.   L. Friberg, M. Rosenqvist, G. Y. Lip.Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182 678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study. EurHeart J 2012, 33: 1500-1510.
3.   S. G. Priori, C. Blomstrom-Lundqvist, A. Mazzanti, et al.2015 ESC Guidelines for the Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death.Rev Esp Cardiol (Engl Ed)2016,69: 176
4.   L. Macle, S. Nattel.Arrhythmias in 2015: Advances in drug, ablation, and device therapy for cardiac arrhythmias. Nat Rev Cardiol 2016, 13: 179
5.   Liu S, Chen J.Marketing strategy of wenxingranuel of Buchang Pharmaceuticals. Bus Econ 2014, 14: 2014.
6.   A. Burashnikov, A. Petroski, D. Hu, et al.Atrial-selective inhibition of sodium-channel current by WenxinKeli is effective in suppressing atrial fibrillation. Heart Rhythm 2012, 9: 125-131.
doi: 10.1016/j.hrthm.2011.08.027
7.   D. Hu, H. Barajas-Martinez, A. Burashnikov, et al. Antzelevitch, "Mechanisms underlying atrial-selective block of sodium channels by WenxinKeli: Experimental and theoretical analysis. Int J Cardiol2016, 207: 326-334.
8.   Y. Minoura, B. K. Panama, V. V. Nesterenko, et al.Effect of WenxinKeli and quinidine to suppress arrhythmogenesis in an experimental model of Brugada syndrome. Heart Rhythm 2013, 10: 1054-1062.
doi: 10.1016/j.hrthm.2013.03.011
9.   Tang QZ, Shi XT, Wang T, et al. Effects of Nardostachyschinensisbatal extract on sodium and calcium channels in rabbit ventricular myocytes. Chin J Cardiol 2004, 32: 267-270.
10.   Xing Y, Gao Y, Chen J, et al, Wenxin-Keli Regulates the Calcium/Calmodulin-Dependent Protein Kinase II Signal Transduction Pathway and Inhibits Cardiac Arrhythmia in Rats with Myocardial Infarction.Evid Based Complement Alternat Med 20113, 2013: 464508.
11.   Hua W, Gao RL, Zhao BC, et al. The Efficacy and Safety of WenxinKeli in Patients with Frequent Premature Ventricular Contractions: A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Trial.Chin Med J (Engl) 2015, 128: 2557-2564.
doi: 10.4103/0366-6999.166026
12.   Wang HP, Zhu HJ, Yan CF.The clinical efficady of WenxinKeli combined with low dose of propafenone in treating frequent atrial premature beats.ModJ IntegrTradi Chin Western Med 2012, 21: 3489-3490, .
13.   Meng Z, Tan J, He Q, et al. WenxinKeli versus Sotalol for Paroxysmal Atrial Fibrillation Caused by Hyperthyroidism: A Prospective, Open Label, and Randomized Study. Evid Based Complement Alternat Med 2015, 2015: 101904.
14.   Heart Rhythm Society of the Chinese Society of Biomedical Engineering; Nao Xin Tong Zhi Committee of the Chinese Association of Integrative Medicine. Expert Consensus on Wenxin Granule for Treatment of Cardiac Arrhythmias. Chin Med J (Engl) 2017, 130: 203-210.
15.   B. J. Shea, J. M. Grimshaw, G. A. Wells, et al.Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews. BMC Med Res Methodol 2007, 7: 10.
doi: 10.1186/1471-2288-7-10
16.   D. Atkins, D. Best, P. A. Briss, et al. Grading quality of evidence and strength of recommendations.BMJ 2004, 328: 1490.
doi: 10.1136/bmj.328.7454.1490
17.   Chen Y, Nie S, Gao H, et al. The effects of wenxinkeli on p-wave dispersion and maintenance of sinus rhythm in patients with paroxysmal atrial fibrillation: a meta-analysis of randomized controlled trials.Evid Based Complement Alternat Med 2013, 2013: 245958.
18.   He M, Lv Z, Yang ZW, et al. Efficacy and safety of Chinese herbal medicine WenxinKeli for ventricular premature be ats: A systematic review. Complement Ther Med 2016, 29: 181-189.
doi: 10.1016/j.ctim.2016.10.007
19.   Li M, QiuR, TianG, et al. WenxinKeli for Ventricular premature complexes with Heart failure: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. Complement Ther Med 2017, 33: 85-93.
doi: 10.1016/j.ctim.2017.06.006
20.   Wang C, Wu W, Wu H, et al. The clinical efficacy and adverse reaction of wenxin granule and amiodarone for patient with atrial fibrillation: A meta-analysis. Int J Clin Exp Med 2017, 10: 14256-14265.
21.   Liang Y, Yao X.Wenxin granule combined with amiodarone in the treatment of heart failure with arrhythmia: a meta-analysis. Chin J Integr Med Cardio Cerebrovasc Dis 2017, 16: 2006-2009.
22.   Shi S, Geng Y,Du B, et al. Treatment of CHD-induced arrhythmias by WenxinKeli combined with bisoprolol: a systematic review and meta-analysis.Beijing J Tradi Chin Med 2017, 1: 6-11.
23.   Li J, Tang H, Li J, Zhou Z, et al.A meta-analysis on effect of WenxinKeli in treatment of arrhythmia.Chin J EvidBasedCardiovasc Med 2011, 2: 84-89, 100.
doi: 10.4236/cm.2011.23015
24.   Bian Z, Liu B, Moher D, et al. Consolidated standards of reporting trials (CONSORT) for traditional Chinese medicine: current situation and future development. Front Med 2011, 5: 171-177.
doi: 10.1007/s11684-011-0132-z
25.   D. Moher, A. Liberati, J. Tetzlaff, D. G. Altman.Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009, 339: b2535.
doi: 10.1136/bmj.b2535
26.   J. P. Ioannidis, S. J. Evans, P. C. Gotzsche, et al. Better reporting of harms in randomized trials: an extension of the CONSORT statement. Ann Intern Med 2004, 141: 781-788.
doi: 10.7326/0003-4819-141-10-200411160-00009
27.   L. Zorzela, Y. K. Loke, J. P. Ioannidis, et al. PRISMA harms checklist: improving harms reporting in systematic reviews. BMJ 2016, 352: i157.
28.   M. Clarke and P. R. Williamson. Core outcome sets and systematic reviews. Syst Rev 2016, 5: 11.
doi: 10.1186/s13643-016-0188-6
29.   Qiu R, Li M, Zhang X, et al. Development of a core outcome set (COS) and selecting outcome measurement instruments (OMIs) for non-valvular atrial fibrillation in traditional Chinese medicine clinical trials: study protocol.Trials 2018, 19: 541.
30.   J. P. Ioannidis, S. Greenland, M. A. Hlatky, et al.Increasing value and reducing waste in research design, conduct, and analysis. Lancet 2014, 383: 166-175.
doi: 10.1016/S0140-6736(13)62227-8
31.   S. Treweek, S. Bevan, P. Bower, et al.Trial Forge Guidance 1: what is a Study Within A Trial (SWAT)?Trials 2018, 19: 139.
32.   S. R.Al-Shahi, E. Beller, J. Kagan, et al.Increasing value and reducing waste in biomedical research regulation and management. Lancet 2014, 383: 176-185.
doi: 10.1016/S0140-6736(13)62297-7
33.   Du H, Dai X. Efficacy and safety of Wenxin Granule in treatment of atrial fibrillation: a Meta-analysis. J Anhui Univ Chin Med2014, 6: 27-30.
34.   Zhao M, Wang H, Xiong F, et al. Effect of Wenxin Granule combined metoprolol on atrial fibrillation: a meta-analysis. China Med 2014, 4: 458-463.
35.   Wang H, Yang B, Zhou S.Efficacy and safety of Wenxin Granules combining amiodarone on atrial fibrillation: a Meta-analysis. Chin J Evid Based Cardiovascu Med 2015, 2: 161-164.
36.   Li M, Qiu R, Sun Y, et al. The Clinical Study of WenxinKeli in the Treatment of Atrial Fibrillation: a Systematic Review. World Sci Technol/Mod Tradi Chin Med Mater Med 2018, 20: 1761-1771.
37.   Du H, Dai X.Efficacy and safety of Wenxin Granule in the treatment of premature ventricular beats: a Meta-analysis. J ClinElectrocardiol 2014,5: 366-369.
38.   Guo R, Jv N, Lin X,et al. Meta-analysis on efficacy and safety of Wenxin Granule combined with metoprolol for treatment of ventricular premature. Chin Tradi Herb Drugs 2016, 6: 1053-1060.
39.   Shen J, Yuan P, Tang J, et al. Efficacy and safety of Wenxin Granules combining betaloc on ventricular premature beat:a Meta-analysis. Chin J EvidBased Cardiovascu Med 2016, 7: 786-791.
40.   Lu J, Liu S, Li J.Wenxin Granules Combined with Metoprolol in the Treatment of Coronary Heart Disease with Ventricular Arrhythmias: A Meta-analysis.J Tradi Chin Med Univ Hunan 2018, 38: 670-676.
41.   Miao P, Zhang M, Zhang L, et al. Effects of Wenxin granule on electrocardiogram. Effects of Wenxin granule on electrocardiogram and clinical symptoms in adults with atrial premature contractions: a Meta-analysis of randomized controlled trials. J Tianjin UnivTradi Chin Med2016, 3: 160-166.
42.   Shi H, Peng W.Meta-analysis of efficacy and safety of Wenxin Granules in the treatment of arrhythmia. China Med Herb 2012,5: 65-66, 68.
43.   He Y, Liu Y, Zou A.Meta-analysis on Wenxin Granules in treatment of arrhythmia. Chin Tradi Herb Drugs 2014, 15: 2277-2282.
44.   ZhangJ, ChenY, LuY, et al. Meta-analysis of therapeutic effect of Wenxin granules combined with amiodarone for arrhythmia in coronary heart disease. Tradi Chin .Drug Res Clin Pharmacol 2017, 2:. 244-248
No related articles found!