Tong-xin-luo capsule for patients with coronary heart disease after percutaneous coronary intervention.

Cochrane Database of Systematic Reviews

Tong-xin-luo capsule for patients with coronary heart disease after percutaneous coronary intervention (Review) Mao C, Fu XH, Yuan JQ, Yang ZY, Chung VCH, Qin Y, Huang Y, Tam WWS, Kwong JSW, Xie W, Tang JL

Mao C, Fu XH, Yuan JQ, Yang ZY, Chung VCH, Qin Y, Huang Y, Tam WWS, Kwong JSW, Xie W, Tang JL. Tong-xin-luo capsule for patients with coronary heart disease after percutaneous coronary intervention. Cochrane Database of Systematic Reviews 2015, Issue 5. Art. No.: CD010237. DOI: 10.1002/14651858.CD010237.pub2.

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TABLE OF CONTENTS HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . SUMMARY OF FINDINGS FOR THE MAIN COMPARISON . . . . . . . . . . . . . . . . . . . BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 4. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.1. Comparison 1 Tong-xin-luo + Convetional treatment vs. Convetional treatment, Outcome 1 Occurrence of angiographic restenosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.2. Comparison 1 Tong-xin-luo + Convetional treatment vs. Convetional treatment, Outcome 2 Occurence of myocardial infarction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.3. Comparison 1 Tong-xin-luo + Convetional treatment vs. Convetional treatment, Outcome 3 Occurence of heart failure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.4. Comparison 1 Tong-xin-luo + Convetional treatment vs. Convetional treatment, Outcome 4 Occurrence of angina. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.5. Comparison 1 Tong-xin-luo + Convetional treatment vs. Convetional treatment, Outcome 5 All-cause mortality. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.6. Comparison 1 Tong-xin-luo + Convetional treatment vs. Convetional treatment, Outcome 6 Mortality due to any cardiovascular event. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.7. Comparison 1 Tong-xin-luo + Convetional treatment vs. Convetional treatment, Outcome 7 Use of revascularization. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . . . . . . . . . . . . INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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[Intervention Review]

Tong-xin-luo capsule for patients with coronary heart disease after percutaneous coronary intervention Chen Mao1 , Xiao-Hong Fu2 , Jin-Qiu Yuan2 , Zu-Yao Yang1 , Vincent CH Chung3 , Ying Qin2 , Yafang Huang2 , Wilson Wai San Tam 4 , Joey SW Kwong5 , Wei Xie6 , Jin-Ling Tang1 1 Division

of Epidemiology, The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong SAR, China. 2 Division of Epidemiology, School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, China. 3 Jockey Club School of Public Health and Primary Care, Chinese University of Hong Kong, NT, Hong Kong, Hong Kong. 4 Alice Lee Centre for Nursing Studies, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. 5 Chinese Cochrane Center, Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu, China. 6 Chinese Medicine, School of Chinese Medicine, Southern Medical University, Guangzhou, China Contact address: Jin-Ling Tang, Division of Epidemiology, The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong SAR, China. [emailprotected]. Editorial group: Cochrane Heart Group. Publication status and date: New, published in Issue 5, 2015. Review content assessed as up-to-date: 12 June 2014. Citation: Mao C, Fu XH, Yuan JQ, Yang ZY, Chung VCH, Qin Y, Huang Y, Tam WWS, Kwong JSW, Xie W, Tang JL. Tong-xinluo capsule for patients with coronary heart disease after percutaneous coronary intervention. Cochrane Database of Systematic Reviews 2015, Issue 5. Art. No.: CD010237. DOI: 10.1002/14651858.CD010237.pub2. Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

ABSTRACT Background Percutaneous coronary intervention (PCI) is a standard treatment for coronary heart disease (CHD). Restenosis, defined as a 50% reduction in luminal diameter at six months after PCI, indicates a need for revascularisation. Restenosis has proven to be a major drawback to PCI. Tong-xin-luo is one of the prophylactic strategies for cardiovascular events in patients after PCI that is widely used in China, but its efficacy and safety have not been systematically evaluated. Objectives To systematically assess the efficacy and safety of Tong-xin-luo capsules in preventing cardiovascular events after PCI in patients with CHD. Search methods We searched the Cochrane Central Register of Controlled Trials in The Cochrane Library, MEDLINE (OVID), EMBASE (OVID), WanFang, Chinese Biomedical Database, Chinese Medical Current Contents, and China National Knowledge Infrastructure from their inception to June 2014. We also searched other resources, including ongoing trials and research registries. We applied no language restrictions. Selection criteria Randomised controlled trials of participants with CHD after PCI were included. Participants in the intervention group received Tongxin-luo capsules for at least three months. Tong-xin-luo capsule for patients with coronary heart disease after percutaneous coronary intervention (Review) Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Data collection and analysis Two review authors independently extracted data and assessed the risk of bias. Any disagreements were resolved by discussion with a third review author. The primary outcomes included occurrence of angiographic restenosis and adverse events; the secondary outcomes included myocardial infarction, heart failure, angina, all cause mortality, mortality due to any cardiovascular event, use of revascularisation, patient acceptability, quality of life and cost-effectiveness. Dichotomous data were measured with risk ratios (RRs) with 95% confidence intervals (CIs). Main results Sixteen studies involving 1063 participants were identified. The risk of bias for fifteen studies was high and along with imprecision and possible publication bias, this lowered our confidence in the results. There was low quality evidence that Tong-xi-luo reduced the rates of angiographic restenosis (RR 0.16, 95% CI 0.07 to 0.34), myocardial infarction (RR 0.32, 95% CI 0.16 to 0.66), heart failure (RR 0.26, 95% CI 0.11 to 0.62), and use of revascularisation (RR 0.26, 95% CI 0.15 to 0.45). There was very low quality evidence for the effect of Tong-xin-luo on all-cause mortality (RR 0.38, 95% CI 0.06 to 2.56), angina (RR 0.24, 95% CI 0.17 to 0.34) and death due to any cardiovascular event (RR 0.31, 95% CI 0.08 to 1.12). Adverse events were seldom reported, and included gastrointestinal reactions and nausea. Authors’ conclusions The addition of Tong-xin-luo to conventional Western medicine may possibly prevent restenosis and recurrence of cardiovascular events in patients with CHD after PCI. However, the data are limited by publication bias and high risk of bias for included studies. Further high-quality trials are required to evaluate the potential effects of this intervention.

PLAIN LANGUAGE SUMMARY Tong-xin-luo capsule for patients with coronary heart disease after percutaneous coronary intervention Review question: What is the efficacy and safety of Tong-xin-luo capsules in preventing cardiovascular events after percutaneous coronary intervention, a procedure involving placing a stent to open up the heart’s blood vessels, in patients with coronary heart disease? Background: Coronary heart disease is a major cause of mortality globally. Percutaneous coronary intervention is regarded as a standard treatment for coronary heart disease to improve symptoms of heart-related chest pain. However, a major drawback of percutaneous coronary intervention is the need for a repeat procedure due to symptoms related to recurring narrowing of the heart’s blood vessels. Previous studies have indicated that Tong-xin-luo capsule, a Chinese herbal medicine product, might be effective in preventing recurrence of narrowing of a blood vessel after percutaneous coronary intervention. Study characteristics: We included sixteen randomised controlled trials (1063 participants) comparing Tong-xin-luo capsules plus conventional treatment with placebo plus/or conventional treatment (literature search date: though June 2014). All studies were undertaken in China. The sample size was from 50 to 178 and the duration of follow-up ranged from three months to two years. Key results: We found that Tong-xin-luo may possibly reduce the risk of narrowing of a blood vessel detected by angiography, cardiovascular events (including myocardial infarction, angina and heart failure) and use of repeat procedure. Adverse events were seldom reported. Quality of evidence: Because of high risk of bias for fifteen studies, imprecision and possible publication bias, the quality of evidence was low or very low for all study outcomes.

S U M M A R Y O F F I N D I N G S F O R T H E M A I N C O M P A R I S O N [Explanation]

Tong-xin-luo compared with placebo/no treatment for patients with CHD after PCI Patient or population: participants with CHD after PCI Settings: China Intervention: Tong-xin-luo capsules Comparison: placebo/no treatment Outcomes

Illustrative comparative risks* (95% CI)

Assumed risk

Corresponding risk

Placebo/no treatment

Tong-xin-luo

Relative effect (95% CI)

No of Participants (studies)

Quality of the evidence (GRADE)

Comments

Occurrence of angio- 134 per 1000 graphic restenosis [follow-up: 6 months]

21 per 1000 (9 to 46)

RR 0.16 (0.07 to 0.34)

595 (6)

⊕⊕

low

Quality of evidence downgraded two levels due to study limitations (lack of blinding in all studies, high risk of reporting bias in one study)

Adverse event

Adverse events were not evaluated as very limited information was reported from original studies

RR 0.32 (0.16 to 0.66)

1306 (13)

⊕⊕

low

Quality of evidence downgraded two levels due to study limitations (lack of blinding in all studies except Wang 2010, high risk of reporting bias in two studies).

Occurence of myocar- Myocardial infarction dial infarction [follow-up: 3-48 months] 22 per 1000

7 per 1000 (3 to 21)

Acute myocardial infarction 53 per 1000

16 per 1000 (6 to 44)

Occurrence of angina 211 per 1000 [follow-up: 3-48 months]

51 per 1000 (36 to 72)

RR 0.24 (0.17 to 0.34)

1210 (11)

⊕

very low

Quality of evidence downgraded two levels due to study limitations (lack of blinding in all studies except Wang 2010, high risk of reporting bias in one study), and one additional level due to publication bias

Occurence of heart fail- 88 per 1000 ure [follow-up: 3-48 months]

23 per 1000 (10 to 54)

RR 0.26 (0.11 to 0.62)

529 (4)

⊕⊕

low

Quality of evidence downgraded two levels due to study limitations (lack of blinding in all studies, high risk of reporting bias in one study)

All-cause mortality 12 per 1000 [follow-up: 3-48 months]

5 per 1000 (1 to 31)

RR 0.38 (0.06 to 2.56)

[419] (4)

⊕

very low

Mortality due to any car- 34 per 1000 diovascular event [follow-up: 3-48 months]

11 per 1000 (3 to 39)

RR 0.31 (0.08 to 1.12)

552 (5)

⊕

very low

Quality of evidence downgraded two levels due to study limitations (lack of blinding in all studies, high risk of reporting bias in one study), and one additional level due to imprecision of the estimate

Use of revascularisation 166 per 1000 [follow-up: 3-48 months]

43 per 1000 (25 to 75)

RR 0.26 (0.15 to 0.45)

806 (8)

⊕⊕

low

Quality of evidence downgraded two levels due to study limitations (lack of blinding in all studies, high risk of reporting bias in two studies)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CHD: coronary heart disease; PCI: percutaneous coronary intervention; CI: confidence interval; RR: risk ratio; NA: not available GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.

BACKGROUND

Description of the condition Cardiovascular diseases (CVDs), which mainly refers to a group of disorders of the heart and blood vessels, are a major cause of death and disability globally (Lonn 2010; Lozano 2012). According to the fact sheet published by the World Health Organization (WHO) in September 2011, CVDs caused about 17.3 million deaths in 2008 and are responsible for 30% of all deaths worldwide (WHO 2011). Moreover, CVDs are expected to account for 46.6% of all deaths by 2020 and 80% of CVD deaths will occur in developing countries (WHO 2002; WHS 2010). Among all deaths attributed to CVDs, about half were due to coronary heart disease (CHD; Go 2014). CHD is a condition in which plaque builds up inside the coronary arteries and can decrease oxygen supply to the heart muscle (NHLBI 2011). According to previous studies, about one in six deaths in the United States were due to CHD in 2010 (Go 2014) and one in six men and one in seven women in the UK died from CHD in 2008 (Bhattarai 2012). Percutaneous coronary intervention (PCI), a non-surgical procedure that involves placing a stent to open up the blood vessels obstructed by plaque, is an effective treatment for CHD (Grech 2003; Singh 2011). However, restenosis has proven to be the major drawback to PCI and frequently causes a return of symptoms and the need for repeated coronary intervention (Kang 2012; Richard 2002; Testa 2009). Restenosis is a recurrence causing significant narrowing in the treated vessel, which is generally considered as a wound healing response to trauma of the vascular wall (Agema 2001; Odell 2006). Clinically, restenosis is defined as recurrent angina pectoris that indicates a need for revascularisation of the treated vessel (Cutlip 2007). It is angiographically defined as a 50% reduction in luminal diameter at six months after PCI. So far, the mechanism of restenosis has not been fully clarified. It is thought that restenosis is due to the combined effect of early elastic recoil in vessels, mural thrombus formation, neointimal proliferation, extracellular matrix formation, and chronic geometric arterial changes (Dangas 1996). According to the study by Giglioli et al, more than 40% of patients have restenosis detected within six months after an angioplasty (Giglioli 2009). This frequently results in renewed symptoms such as angina that hamper the long-term efficacy of PCI (Fattori 2003; Rajaqopal 2003). There are many strategies aimed at preventing cardiovascular events in patients after PCI, which include using antiplatelet drugs, thrombin inhibitors, and Tongxin-luo. However, some of these interventions have adverse effects (Dörffler 2005; Serruys 1995; Rosanio 1999).

Description of the intervention

Tong-xin-luo capsule is a drug that has been studied since 1995 based on the theory of Chinese herbal medicine.The recommended dose range is 1.14 g to 1.52 g in three to four capsules (0.38 g in each capsule) and administered three to four times a day, with a total dose of between 3.5 g and 6.0 g per day. The treatment is given as a four-week course (Wu 2001; Zhou 2011). Currently, Tong-xin-luo capsule is widely used for treating cardiac-cerebral vascular diseases in China. Its effect on prevention and treatment of restenosis among CHD patients after PCI has become an important topic in both Chinese and Western medical research areas. Previous studies indicated that Tong-xin-luo can effectively relieve angina, reduce the frequency of acute attacks of angina, and prevent restenosis of stents (Wang 2003; Zhang 2004; Zhou 2007 a; Zhu 2004). Potential interactions with other drugs are unclear. Related adverse events have been reported which include gastrointestinal tract symptoms, gingival bleeding, and increased partial thromboplastin time (Nong 2000).

How the intervention might work The main composition of Tong-xin-luo capsules is complex and includes Hirudo, Radix Ginseng, Scorpio, Eupolyphaga Seu Steleophage, Scolopendra, Periostracum Cicadae, Lignum Dalbergiae Odoriferae, Radix Paeoniae Rubra, and Borneolum Syntheticum (Zhou 2011). Previous studies have shown the following. • Hirudin-like materials, which are produced by Scorpio, Hirudo, Eupolyphaga Seu Steleophage, and Scolopendra (Huntington 2003; Yu 2011; Zhou 1997), can stop blood clotting by reducing the secretion of extracellular matrix (Paul 1994) and suppressing the aggregation of platelets and inflammatory cells (Chen 2007; Modi 1995). • Radix Ginseng has cardiokinetic function as well as inhibiting the platelet adhesion reaction and thrombosis formation (Pei 1986; Xu 1988). • Radix Paeoniae Rubra dilates coronary arteries, causes thrombolysis, improves myocardial ischemias, inhibits proliferation of vascular smooth muscle cells, and prevents onset of endothelial injury (Lu 2006; Ruan 2003; Wang 2008). • Periostracum Cicadae is an anticonvulsive and significantly slows heart rate (Zheng 1998). • Scolopendra extraction could increase blood vessel perfusion flow and strengthen cardiac contractility (Chen 1985). • Eupolyphaga Seu Steleophage could improve tolerance to hypoxia and increases cardiac output (Nong 1989).

Why it is important to do this review Due to incomplete evidence on the benefits and possible adverse effects of Tong-xin-luo capsule, a systematic review on the therapeutic efficacy and safety of Tong-xin-luo capsule use is needed.

The results of our review may shed new light on the prevention of cardiovascular events for patients with coronary heart disease after PCI and may also provide new treatment methods for cardiovascular disease with reduced expense and side effects.

OBJECTIVES To systematically assess the efficacy and safety of Tong-xin-luo capsules in preventing cardiovascular events after PCI in patients with CHD.

Secondary outcomes

• Occurrence of myocardial infarction (MI), heart failure, or angina • All cause mortality • Mortality (death) due to any cardiovascular event • Use of revascularisation, including PCI and coronary artery bypass graft surgery • Patient acceptability • Quality of life • Cost-effectiveness

Search methods for identification of studies

METHODS

A comprehensive search strategy was formulated in an attempt to identify all relevant studies regardless of publication status. Electronic databases were searched and handsearching of journals was carried out.

Criteria for considering studies for this review

Electronic searches

Types of studies Randomized controlled trials (RCTs). Single-arm trials, animal studies and reviews were excluded.

Types of participants Participants were male or female of any age or ethnic origin with CHD after PCI. Participants were eligible regardless of recruitment through clinical or community settings.

Types of interventions Tong-xin-luo capsule was regarded as the intervention in our study. Tong-xin-luo capsule used alone after PCI and with a treatment duration of no less than three months was compared with at least one valid comparator, including no intervention, placebo, or an effective Western medicine intervention supported by reasonable clinical evidence.

Types of outcome measures We considered the following outcome measures.

Primary outcomes

• Occurrence of angiographic restenosis • Adverse events

We searched the following main electronic databases, with no restriction in publication language. • Cochrane Central Register of Controlled Trials (CENTRAL Issue 5, 2014; The Cochrane Library). • MEDLINE (OVID, 1950 to June week 1 2014). • EMBASE (OVID, 1947 to week 23 2014). • WanFang (1998 to August week 2 2014). • China National Knowledge Infrastructure (CNKI; 1993 to April week 2 2013). • Chinese Biomedical Database (CBM; 1978 to April week 2 2013). • Chinese Medical Current Contents (CMCC; 1994 to April week 2 2013). The search strategies used can be found in Appendix 1. No language restrictions were applied. Searching other resources We searched the following clinical trial registries for ongoing and unpublished trials from 1994 to June 2013. • Current Controlled Trials (http://www.controlledtrials.com). • WHO International Clinical Trials Registry Platform (ICTRP; http://apps.who.int/trialsearch/). • ClinicalTrials.gov (www.clinicaltrials.gov). • Chinese Clinical Trial Register (www.chictr.org). • China Master’s Theses Full-text Databases (CMFD; http:// oversea.cnki.net/kns55/brief/result.aspx?dbPrefix=CMFD). • China Doctoral Dissertation Full-text Database (CDFD; http://oversea.cnki.net/kns55/brief/result.aspx? dbPrefix=CDFD).

• China Proceedings of Conference Full-text Database ( CPCD). The search strategies used can be found in Appendix 1. Handsearching

Handsearching was not performed as the journals we would have planed to search manually (including China Journal of Chinese Materia Medica, Chinese Journal of Basic Medicine in Traditional Chinese Medicine, and Chinese Journal of Integrated Traditional and Western Medicine) were included in WanFang database.

Risk of bias assessments are presented in tables on the following domains (Higgins 2011). • Sequence generation. • Allocation concealment. • Blinding. • Incomplete outcome data. • Selective outcome reporting. • Other bias. The risk of bias for each domain was categorized as: • Low risk of bias; • High risk of bias; • Unclear risk of bias.

Data collection and analysis Two authors independently carried out selection of studies, data extraction, and quality assessment. Data analysis was conducted using Review Manager Version 5.1 (RevMan 2008) according to the statistical guidelines referenced in the current version of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). Selection of studies Two authors (XF, ZY) independently scanned the titles and abstracts of every record retrieved for eligibility assessment. The fulltexts of any literature with unclear information in the title or abstracts, and potential eligible studies were retrieved for clarification. All studies selected by the two authors were cross checked. Any disagreement was resolved by discussion with a third author (CM). Data extraction and management

Measures of treatment effect Dichotomous data (occurrence of angiographic restenosis, adverse events, myocardial infarction, heart failure, angina, all cause mortality, mortality due to any cardiovascular event, use of revascularisation) were analysed using risk ratios (RRs) with 95% confidence intervals (CIs). It has been shown that RR is more intuitive (Boissel 1999) than the odds ratio (OR) and that OR tend to be interpreted as RR by clinicians (Deeks 2000), which leads to an overestimate of the effect. We planned to analyse continuous outcomes using weighted mean differences (with 95% CI). Standardized mean differences would have been employed if different measurement scales were used. Skewed data and non-quantitative data would have been presented descriptively.

Unit of analysis issues

Two authors (XF, YQ) independently extracted data using a standard form pre-designed for this review. The data extracted were as follows: study characteristics (authors, location, title, etc.), patient characteristics (number of patients, age, gender, race, baseline disease severity, etc.), intervention, control, methodological information (randomisation, allocation concealment, blinding, loss to follow-up, selective outcome reporting),outcomes. The authors of the original studies were consulted for unclear or missing information where necessary. Any disagreement were resolved by discussion.

We did not include any cluster randomised trials or cross-over studies in this review. All included studies are two-arm trials and no control group was used more than once in the meta-analysis. When assessing event data, we avoided counting more than one outcome event for any participant. Where we were unclear about the data (for example, where a study reported numbers of myocardial infarctions, but did not report the number of people who experienced a myocardial infarctions) we asked authors for further information.

Assessment of risk of bias in included studies

Dealing with missing data

The risk of bias in selected studies was independently assessed by two authors (YQ, VC), under the guidance of the Cochrane Heart Group and using the tool described in the Cochrane Handbook for Systematic Review of Interventions (Higgins 2011). Any disagreement was resolved by a third author (CM). In order to confirm and validate the methods of allocation concealment and the randomisation procedure, the original authors of all trials were contacted.

When there were missing data, we contacted the original authors of the study to obtain the relevant missing data. If missing data could not be obtained, an imputation method was used. We used sensitivity analysis to assess the impact on the overall treatment effects of inclusion of trials which did not report an intention-totreat analysis, had high rates of participant attrition, or had other missing data.

Assessment of heterogeneity The clinical and methodological heterogeneity were evaluated by considering the variability in important participant factors among trials and trial factors (randomisation concealment, blinding of outcome assessment, losses to follow-up, treatment type, co-interventions), respectively. Statistical heterogeneity was tested using the Chi2 test (significance level 0.1; Lau 1997) and I2 statistic (0% to 40%: minimal heterogeneity; 30% to 60%: may represent moderate heterogeneity; 50% to 100%: substantial heterogeneity). We planned to explain the source of heterogeneity by subgroup analysis and meta-regression. Assessment of reporting biases We used funnel plots to assess potential publication bias (Egger 1997) for the meta-analyses with the outcomes MI and angina, as these analyses included 10 or more studies (Higgins 2011; Sterne 2001). Data synthesis Each outcome was combined and calculated using the statistical software RevMan 5.1 (RevMan 2008), according to the statistical guidelines referenced in the current version of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). All the meta-analyses were performed with a fixed-effect model using the Mantel-Haenszel method as no significant heterogeneity was found (I2 < 50% or P > 0.1).

• Patient characteristic (age, sex). • Types of treatment (Western medicine alone, Western medicine plus Tong-xin-luo). • Follow-up period. • Type of stent.

Sensitivity analysis We planned to perform sensitivity analysis to explore the source of heterogeneity as follows, however there were insufficient numbers of studies. • Quality components, including full-text publications versus abstracts, preliminary results versus final results, published versus unpublished data. • Risk of bias (by omitting studies that were judged to be at high risk of bias).

RESULTS

Description of studies For a detailed description of studies, see Characteristics of included studies.

Subgroup analysis and investigation of heterogeneity

Results of the search

We planned to perform subgroup analyses based on the following factors. However, subgroup analyses were not carried out because: there were insufficient data in the original studies allow us to classify the included studies into different subgroups according the pre-specified factors.

As shown in the flow chart (Figure 1), our search in electronic bibliographic databases yielded 2168 citations, of which 59 were classified as potentially relevant and were subjected to full text assessment. Sixteen studies with 20 citations met the defined inclusion criteria.

Figure 1. Flow chart of study selection

Included studies

years. All participants showed objective symptoms of CHD and had received a successful PCI. The duration of follow-up ranged from three months (Dai 2011) to two years (Chen 2011) in studies where length of follow-up was provided.

Design of included studies

All the included studies were RCTs of single centre, parallel design, with a control group; one study used a randomised, double-blind, placebo-controlled design (Wang 2010). All included studies were conducted in China, and were performed in hospital settings.

Participants in included studies

A total of 1603 participants were included in the 16 trials, and the number of participants in the studies ranged from 50 (Di 2012) to 178 (Zhang 2009a). The age of participants ranged from 30 to 78

Interventions in included studies

All included trials compared Tong-xin-luo capsule plus conventional treatment with the same conventional treatment alone except one study (Wang 2010), which compared Tong-xin-luo capsule plus conventional treatment with placebo plus the same conventional treatment. Participants all received aspirin, clopidogrel, and low molecular weight heparin after PCI as background therapy. Eight studies reported the use of statins as routine treatment, of which four studies prescribed atorvastatin, one prescribed

pravastatin, and three studies did not report which class of statin was prescribed. Other treatments including beta-blockers, nitrates, and angiotension conversion enzyme inhibitors were selectively applied according to illness status of participants. Tong-xin-luo capsule (three to four capsules, three times per day) was initiated on the day of PCI. In one study (Wu 2010), participants in the treatment group began to take Tong-xin-luo seven days before PCI. The treatment duration and time of follow ranged from three months (Yang 2009a) to two years (Zhang 2009a).

Outcome measures of included studies

• Six studies (Chen 2011; Dai 2011; Liang 2010; Wu 2010; Xiao 2007; Zhou 2007b) reported on the incidence of restenosis. • Three studies (Di 2012; Huang 2010; Zhang 2009a) mentioned occurrence of adverse events. • Five studies (Dong 2012; Huang 2010; Liang 2010; Wang 2009a; Wu 2010) reported on the incidence of acute myocardial infarction (AMI), eight studies (Di 2012; Li 2004; Wang 2010; Xiao 2007; Yang 2009a; Zhang 2009a; Zheng 2010; Zhou 2007b) reported on the incidence of myocardial infarction (MI). • Eleven studies (Chen 2011; Di 2012; Li 2004; Liang 2010; Wang 2009a; Wang 2010; Wu 2010; Xiao 2007; Yao 2006; Zhang 2009a; Zhou 2007b) assessed occurrence of angina. • Four studies (Chen 2011; Xiao 2007; Yang 2009a; Zhang 2009a) measured occurrence of heart failure. • Four studies (Di 2012; Wang 2010; Yang 2009a; Zhang 2009a) reported on all-cause mortality; five studies (Dong 2012; Huang 2010; Xiao 2007; Yang 2009a; Zhang 2009a) had data available for mortality due to any cardiovascular event. • Eight studies (Di 2012; Dong 2012; Huang 2010; Wu 2010; Yang 2009a; Zhang 2009a; Zheng 2010; Zhou 2007b) assessed the use of revascularisation, including PCI and coronary artery bypass graft surgery. • No studies reported mortality (death) due to restenosis after

PCI. None of the studies mentioned patient acceptability, quality of life or cost-effectiveness. Regarding study outcomes, all studies reported the number of patients who experienced related event, except one study (Li 2004) which reported the number of events in each group. Excluded studies In total, thirty eight articles were excluded on the basis of their fulltext versions for the following reasons (Characteristics of excluded studies): six studies (Chang 2004; Qu 2011; Su 2000; Xiao 2004; Zhang 2008; Zhang 2009b ) included patients who did not receive coronary stenting; one trial (Jiang 2008) did not use Tong-xinluo as an intervention; the intervention period of Tong-xin-luo in 14 articles (Chen 2007; Fan 2008; Fu 2012; Han 2009; Han 2011; Liu 2009; Lu 2012; Wang 2009c; Xu 2007; Zhang 2007; Zhang 2006; Zhang 2005; Zhao 2010; Zhao 2011) was less than three months; two studies (Gao 2007; Xu 2008) were not RCTs; 14 studies (Guo 2012; Kuang 2011; Li 2012; Li 2008; Ma 2009; Tao 2012; Tu 2006; Wang 2007; Wang 2012; Wang 2009b; Yang 2009b; Yang 2010; Yang 2012; Zhang 2010) didn’t repot relevant outcomes; and for one study (Hou 2008) only an abstract was published with no data available. We found one on-going study (Han 2012; Characteristics of ongoing studies).

Risk of bias in included studies All included studies, except for the study by Wang et al (Wang 2010), were considered to have a high risk of bias as at least one domain of methodology was judged at high risk of bias. We tried to contact the study authors to clarify domains of unclear risk of bias but received no reply. Detailed information for the assessment of risk of bias for each included study is described in risk of bias tables under Characteristics of included studies, and authors’ judgements about each risk of bias item are presented in Figure 2.

Figure 2. Risk of bias graph: review authors’ judgements about each risk of bias item presented as percentages across all included studies.

Allocation All the included studies mentioned randomisation. However, only three studies (Chen 2011; Yang 2009a; Zhang 2009a) reported allocation sequence generated by using random number tables or drawing of lots. None of the others described the method of randomisation in details. None of the included studies mentioned allocation concealment. Blinding Only one study (Wang 2010) mentioned blinding, but no detailed information about the blinding method was provided. We considered other studies to be at high risk of bias because blinding was not reported and placebo was not used. Patients, doctors and other key study personnel were highly likely to know the allocation. Incomplete outcome data One study (Yang 2009a) reported one withdrawal before randomisation. None of the studies mentioned losses to follow-up after randomisation, except that more than half of participants in one study (Xiao 2007) did not undergo coronary angiography, so the occurrence of angiographic restenosis was not reported. There was no loss to follow-up in terms of the other outcomes in this study. None of the other studies reported withdrawals or loss to follow-up. None of the studies mentioned intention-to-treat analysis (ITT).

Two studies that did not report all the outcomes listed in the methods section were judged as having high risk of bias (Yang 2009a; Zhou 2007b). Other potential sources of bias The included studies may have been influenced by the small study effect as none of the included studies mentioned sample size calculation and most of them were small (ranged from 50 to 178 patients). However, baseline information including sex, age, comorbidity, types of coronary pathological changes, number of stents implanted and other risk factors appeared to be balanced between Tong-xin-luo groups and control groups in 13 studies (P > 0.05), and the usage of Tong-xin-luo capsule and conventional treatment were similar, so we considered these 13 trials to be of low risk of bias from other potential sources. The other three studies (Liang 2010; Zheng 2010; Zhou 2007b) were judged as having an unclear risk of bias, because sufficient information was not provided on baseline characteristics.

Effects of interventions See: Summary of findings for the main comparison Primary outcome measures

1. Occurrence of angiographic restenosis

Selective reporting No study protocols were available for the included studies. Therefore, most studies were considered to have an unclear risk of bias.

Six trials (Chen 2011; Dai 2011; Liang 2010; Wu 2010; Xiao 2007; Zhou 2007b) involving 595 participants had relevant data on angiographic restenosis investigated at 6 month follow-up

comparingTong-xin-luo plus conventional treatment with conventional treatment alone. Tong-xin-luo plus conventional treatment was better at reducing the risk of occurrence of angiographic restenosis (6/305 vs. 41/290, RR 0.16, 95% CI 0.07 to 0.34, P < 0.00001; see Analysis 1.1).

2. Adverse events

Meta-analysis for the outcome of adverse events was not performed due to insufficient data. In one study there was one case of gastrointestinal reaction relieved without medication in the treatment group and one case of gastrointestinal reaction relieved after symptomatic treatment in the control group (Di 2012). Three patients had mild nausea and mild pain in the upper left abdomen at the beginning of Tong-xin-luo treatment in one study (Zhang 2009a); the symptoms disappeared once the patients started taking the medication between meals. No severe adverse events were reported in these two studies. One study reported no adverse events in the treatment group (Huang 2010).

incidence of angina in the Tong-xin-luo group (33/616 vs. 137/ 594, RR 0.24, 95% CI 0.17-0.34, P 0.00001; See Analysis 1.4).

4. All-cause mortality and mortality due to any cardiovascular event

Four studies of 419 participants reported all-cause mortality. Two studies (Di 2012; Wang 2010) reported no deaths in either treatment or control groups, so the estimate was pooled from the two other studies (Yang 2009a; Zhang 2009a). There was no evidence of a difference between the Tong-xin-luo group and the control group (1/219 vs. 3/200, RR 0.38, 95% CI 0.06-2.56, P 0.32; see Analysis 1.5) Five studies (Dong 2012; Huang 2010; Xiao 2007; Yang 2009a; Zhang 2009a) consisting of 532 participants reported outcomes of mortality due to cardiovascular events, and there was some evidence that Tong-xin-luo plus conventional treatment reduced the risk of death due to cardiovascular events in comparison to conventional treatment alone, though the test did not reach statistic significance (1/285 vs. 7/267, RR 0.31, 95% CI 0.08-1.12, P 0.07; see Analysis 1.6).

Secondary outcome measures 5. Use of revascularisation 1. Occurrence of MI

Five trials (Dong 2012; Huang 2010; Liang 2010; Wang 2009a; Wu 2010) with 453 participants reported on the outcome of AMI, and eight trials (Di 2012; Li 2004; Wang 2009a; Xiao 2007; Yang 2009a; Zhang 2009a; Zheng 2010; Zhou 2007b) with 853 patients reported MI. The pooled estimate of these 13 studies showed that the addition of Tong-xin-luo to conventional treatment reduced the risk of MI compared to conventional treatment alone (7/659 vs. 27/647, RR 0.32, 95% CI 0.16 to 0.66, P 0.002; see Analysis 1.2).

Pooled analysis of eight studies (Di 2012; Dong 2012; Huang 2010; Wu 2010; Yang 2009a; Zhang 2009a; Zheng 2010; Zhou 2007b) including 806 participants showed a significant effect in favour of the addition of Tong-xin-luo to conventional treatment (15/409 vs. 58/397, RR 0.26, 95% CI 0.15 to 0.45, P < 0.00001; see Analysis 1.7).

6. Patient acceptability, quality of life or cost-effectiveness

Meta-analyses were not done as none of the included studies reported these outcomes.

2. Occurrence of heart failure

Sensitivity analysis

Four studies (Chen 2011; Xiao 2007; Yang 2009a; Zhang 2009a) of 529 participants investigated occurrence of heart failure. The pooled results showed that the combined treatment of Tong-xinluo and conventional treatment reduced the risk of heart failure (6/ 268 vs. 23/261 RR 0.26, 95% CI 0.11-0.62, P 0.003; See Analysis 1.3).

Sensitivity analyses by study quality were not performed because most of the included studies were considered to have high risk of bias. There was an insufficient number of studies for meta-analysis after removing studies at high risk of bias. Publication bias

3. Occurrence of angina

A total of 11 RCTs involving 1210 participants (Chen 2011; Di 2012; Li 2004; Liang 2010; Wang 2009a; Wang 2010; Wu 2010; Xiao 2007; Yao 2006; Zhang 2009a; Zhou 2007b) provided data on occurrence of angina. Pooled results demonstrated a reduced

Funnel plots were used to assess potential publication bias for the outcomes of MI and angina as more than 10 trials were included for each of them. A symmetrical funnel plot of MI indicate no risk of publication bias (see Figure 3), but an asymmetrical funnel plot of angina suggested that high risk of publication bias existed (see Figure 4).

Figure 3. Funnel plot of comparison: 1 Tong-xin-luo + Conventional treatment vs. Conventional treatment, Outcome: 1.2 Occurence of myocardial infarction.

Figure 4. Funnel plot of comparison: 1 Tong-xin-luo + Conventional treatment vs. Conventional treatment, Outcome: 1.4 Occurrence of angina.

cant when the sample size increased. However, the study findings should be interpreted with caution because most of the included studies were at high risk of bias.

DISCUSSION Summary of main results This systematic review included 16 RCTs which evaluated the effects of Tong-xin-luo in addition to conventional treatment. The meta-analysis demonstrated that Tong-xin-luo capsule in combination with conventional Western medicine was significantly more effective in preventing angiographic restenosis, cardiovascular events (MI, angina and heart failure), and revascularisation, when compared with conventional Western medicine alone. There was some evidence that the addition of Tong-xin-luo to conventional treatment reduced the risk of all-cause mortality or mortality due to any cardiovascular event though the estimates failed to achieve statistical significance. This might be due to small sample size. The statistical heterogeneity was low in all meta-analyses. No severe adverse events were observed in the patients treated with Tong-xin-luo. The effect of Tong-xin-luo was generally not obvious in included trials, but the pooled estimates from meta-analyses were signifi-

Overall completeness and applicability of evidence Sixteen RCTs involving 1063 patients were included in this review. This review examined the efficacy of Tong-xin-luo in patients with CHD after PCI. Although the age and gender of participants in the included trials were representative of CHD patients who undergo successful PCI operations, the sample size of the included trials was generally small. Furthermore, all participants were recruited from Chinese populations. This may limit the generalizability of the study results to patients of other ethnicities.

Quality of the evidence Because of the limitations of the included studies, including imprecision and publication bias, the quality of evidence was considered low or very low for most study outcomes of this systematic review. Most publications provided very limited information about

trial design and methodology. Only three studies described the methods of randomisation. Methods of allocation concealment or blinding were not mentioned in most of the included studies. Lack of blinding may have lead to an unbalanced prescription of other treatments such as statins, which may have influenced the results. As most of the included studies generally did not provide sufficient information for us to assess whether the prescription of other medicines were consistent and balanced, the potential influence is unclear. In addition, no included studies mentioned sample size calculation and most of the included studies consisted of small numbers of participants. As smaller studies are usually less rigorous than large scale studies and are more likely to show a large treatment effect (Pereira 2012), the treatment effects of Tong-xinluo need to be evaluated by future large-scale RCTs. Additonal potential problems in the design and conduct of traditional Chinese medicine research (Wang 2007) should also be noted. Thus, although this review shows a potentially protective effect of Tongxin-luo, the results should be interpreted with caution. Future research is very likely to change the estimates.

Potential biases in the review process We attempted to minimise bias in the review process. One of the major challenges to conducting reviews across different cultural medical disciplines is the language barrier and resulting insufficient literature search (Wu 2013). A comprehensive search without language restrictions was conducted to identify all relevant studies. Study selection, assessment of risk of bias and data extraction were independently carried out by two review authors. The review was strictly conducted according to the protocol, however, potential biases might still exist. Asymmetrical funnel plots of angina suggest that publication bias may be present; this might lead to overestimates of effect size of Tong-xin-luo in reducing the risk of angina. In addition, the inclusion criteria of participants in different trials varied from each other, with some trials only including patients with AMI, while others only included patients with angina; this suggests that there may be some clinical heterogeneity among included studies. Lastly, the overall analysis did not consider the varying trial durations and drug usage as part of routine treatment. However, no significant heterogeneity was identified in the meta-analysis, which suggests the impact of trial duration and drug usage on the treatment effect was low.

Agreements and disagreements with other

studies or reviews We did not identify any other systematic reviews with a focus on Tong-xin-luo capsule for restenosis after PCI in patients with CHD. Two systematic reviews on the efficacy of Tong-xin-luo were identified. One included 18 studies and assessed the effects of Tong-xin-luo in patients with unstable angina pectoris (Wu 2006). This study’s results suggested that Tong-xin-luo reduces the risk of AMI, angina and need for revascularisation, but the poor quality of included studies was of concern. The other review included only two trials assessed the efficacy for acute cerebral infarction (Zhuo 2008) and was unable to determine whether Tong-xin-luo has a favourable effect or not in acute ischaemic stroke.

AUTHORS’ CONCLUSIONS Implications for practice This systematic review indicated that Tong-xin-luo may possibly reduce incidence of angiographic restenosis, revascularisation, and CVDs, without causing severe adverse effects, in patients with CHD after PCI. However, these results should be considered as hypothesis generating rather than hypothesis testing due to the small sample size, high risk of bias in the included studies, publication bias and low quality of evidence.

Implications for research This systematic review has important implications for future research. Firstly, further studies of high quality are needed. Improvement of methodological quality should be achieved, including use of placebo and clear descriptions of randomisation and allocation concealment. Secondly, future studies should report quality of life, patient acceptability and cost. Morever, most of the included studies were small. More studies with large sample sizes are needed to verify the protective effect of Tong-xin-luo. Lastly, cost-effectiveness studies of Tong-xin-luo are also needed as such evidence is lacking.

ACKNOWLEDGEMENTS We would like to thank the members of the Cochrane Heart Group for their advice during the development of the protocol.

REFERENCES

References to studies included in this review Chen 2011 {published data only} Chen ZQ. Effect of Tongxinluo capsule on platelet activity and function of vascular endothelium functions as well as prognosis at different stage in patients with acute coronary syndrome after undergoing percutaneous coronary intervention [ South China Journal of Cardiovascular Diseases 2011;suppl: 84. ∗ Chen ZQ, Hong L, Wang H, Yin Q. Effect of Tongxinluo capsule on platelet activities and vascular endothelium functions as well as prognosis in patients with acute coronary syndrome undergoing percutaneous coronary intervention [ Chinese Journal of Integrated Traditional and Western Medicine 2011;31(04):487–91. Chen ZQ, Hong L, Wang H, Yin Q, Lu LX, Lai YL. Effect of Tongxinluo capsule on platelet activities and vascular endothelium functions at different stages in patients with acute coronary syndrome undergoing percutaneous coronary intervention [ Chinese Pharmaceutical Journal 2012;47(4):311–5. Dai 2011 {published data only} Dai GF, Yang SJ. Clinical observation for the effect of Tong-xin-luo capsules in preventing restenosis in patients with coronary heart disease after percutaneous coronary intervention [

PCI

]. Guangming Journal of Chinese Medicine 2011;26(9):1823–4. Di 2012 {published data only} Di J. Research on the Effect of Tongxinluo capsule on the Instent Restenosis of Small Vessels and Long Affection in Coronary Artery [ thesis]. Nanjing: Nanjing University of Chinese Medicine, 2012. Dong 2012 {published data only} Dong SQ, Dong YW. Influence of Tongxinluo on inflammatory and cytokinesendothelial function in patients with acute myocardial infarction after percutaneous coronary intervention [ Chinese Journal of Clinicians (electronic edition) 2012;6(7): 1865–7. Huang 2010 {published data only} Huang B. Influence of Tongxinluo on inflammation reaction and endothelial function in patients with acute myocardial infarction after percutaneous coronary intervention

[ Journal of New Chinese Medicine 2010;42(9):22–4.

Li 2004 {published data only} Li YW. Research on the Effects of Tongxinluo Capsules on Local Cerebral Blood Flow in Patients with Cerebral Infarction [ ]. ]. Journal of Bethune Military Medical College 2004;2(2):75–7. Liang 2010 {published data only} Liang YM, Wang ZJ, Su XY. The effect of Tongxinluo capsules on coronary restennosis of patients with acute myocardial infarction after percutaneous coronary intervention ].

[ Chinese Journal of TCM WM].Critical Care 2010;17(003): 175–6. Wang 2009a {published data only} Wang YH, Shi HN. Effect of Tongxinluo capsules to prevent restenosis in patients after percutaneous intervention ]. [ Modern Journal of Integrated Traditional Chinese and Western Medicine 2009;18(1):39. ]. Wang 2010 {published data only} Wang XD, Lou B. Effect of Tongxinluo Capsule on Restenosis after Coronary Artery Stent Implantation in Patients with Type-2 Diabetes Mellitus [ 2 Journal of Nanjing TCM University 2010;26(006):464–7.

Wu 2010 {published data only} Wu ZY, Yang DC, Hou B, Chen YG. Effects of Tongxinluo Capsules on interventional therapy of patients with unstable angina. China Medical Herald, 2010, 20: 012. ].

[ ][Master’s China Medical Herald 2010;7(20):17–20. Xiao 2007 {published data only} Xiao HB, Zhang DD, Gu J. Effects of tongxinluo on C-reactive protein and clinical prognosis in patients after coronary stenting [

C ]. Cardiac Intervention 2007;16

(8):520–2.

Yang 2009a {published data only} ∗ Yang W. The protective effects of Tongxinluo capsule on myocardium after reperfusion in patients with acute myocardial infarction [

PCI

][Master’s 17

thesis]. Shaanxi: Shaanxi University of Chinese Medicine, 2009. Yang W, Wang S, Xu XH, Zhang CF. NA

Fan 2008 {published data only} Fan SM. Treatment Effects of Tongxinluo capsule on acute myocardial infarction after coronary stent

[ PCI Chinese Community Doctors 2012;30:8. Yang W, Xu XH, Wang S, Zhang CF.

Fu 2012 {published data only} Fu DH, Song XL, Feng]. CH. Clinical observation of Tongxinluo capsules in treating patients with angina after PCI

PCI [ Chinese Journal of Difficult and Complicated Cases 2012;11 (6):452–3. Yao 2006 {published data only} Yao FH, Liu N, Ge GY. Clinical study of reconstriction after PCI operation in patients with coronary disease intervened by Tongxinluo capsule

]. [ Journal of Guiyang College of Traditional Chinese Medicine 2012;34(3):171–2.

[ PCI Chinese Journal of Difficult and Complicated Cases 2006;5 (3):191–2.

Zhang 2009a {published data only} Zhang XP, Zhang Y. Long-term effect of Tongxinluo in patients with acute myocardial infarction after coronary stenting

Gao 2007 {published data only} Gao CY, Yang L, Zhang J, Wu YL. The long-term efficacy of Tongxinluo in patients after percutaneous coronary intervention [ Hebei Medical Journal 2007;29(10):1067–8.

[ Chinese Remedies & Clinics 2009;9(3):243–4.

Zheng 2010 {published data only} Zheng H, Teng ZH, Ma LQ. The effect of Tongxinluo capsule on level of serum CRP and blood lipid in patients with ACS post PCI [

[ Qinghai Medical Journal 2008;38(1):8–10.

Guo 2012 {published data only} Guo YH, Wang Y. Evaluation of the therapeutic effect of Tongxinluo for acute myocardial infarction using 99 Tcm -MIBI SPECT imaging [99 Tcm – ].

MIBI Chinese Journal of Nucleau Medicine and Molecular Imaging 2012;32(2):127–30. C–

]. Chinese Journal of Difficult and Complicated Cases 2010;9(7):487–8.

[ Journal of Emergency in Traditional Chinese Medicine 2009; 18(5):730–1.

Zhou 2007b {published data only} Zhou J, Guo JT. Clinical Study of Tongxinluo on Preventing Re-stenosis of Stents in CHD [ Hebei Medicine 2007;13(10):1188–91.

References to studies excluded from this review Chang 2004 {published data only} Chang SF, Zhao M. Clinical observation for Tongxinluo in the treatment of 68 cases of unstable angina pectoris 68 ]. [ Modern Journal of Integrated Traditional Chinese and Western Medicine 2004;13(2):189. Chen 2007 {published data only} Chen ZQ, Lai YY, Hong L, Wang H, Qiu Y, Yin QL, et al. The effects of Tongxinluo capsule on platelet activity and vascularendothelium function in patients with ACS after PCI [ Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2007;9(7):460–3.

Han 2009 {published data only} Han XT. Study of the changes of myeloperoxidase concentration in plasma and the interventional effect of Tongxinluo capsule on patients with unstable angina

Han 2011 {published data only} Han XT, Cui XJ, Li YR, Chu FY. The effect of Tongxinluo on blood lipid, hs-CRP and MMP-9 in patients with unstable angina pectoris after PCI [ PCI Journal of Emergency in Traditional Chinese Medicine 2011; 20(6):873–4.

Hou 2008 {published data only} Hou AJ, Liu MY, Zhao HY, Zhang M, Yuan L, Jin YZ, et al. The effect of Tongxinluo on restenosis in patients with ACS [ Chinese Journal of Cardiology 2008;36:221–2.

Jiang 2008 {published data only} Jiang XG, Yang YB, Qi HW, Yang M. Research of prevention effect of traditional Chinese medicine on ]. percutaneous coronary intervention restenosis after [

]. 18

Heilongjiang Journal of Traditional Chinese Medicine 2008; 37(4):58–9.

Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Cricitical Care 2000;7(2):119. Tao 2012 {published data only} Tao WG, Zhu KY. Curative effect of Tongxinluo in treatment of angina after percutaneous coronary

Kuang 2011 {published data only} Kuang B, Yang Y. Protection of Tongxinluo capsule against myocardial injury in patients after elective percutaneous coronary stenting posting

intervention (PCI) operation [ ].

[ Modern Hospital 2011;11(5):21–3.

]. Medical Innovation of China 2012;9(5):9–10.

Li 2008 {published data only} Li MJ. Inflammatory reaction and change of vascular endothelial function after percutaneous coronary intervention and the effect of Tongxinluo

Tu 2006 {published data only} Tu YP, Lei MJ, Zeng LF, Gong AB, Wei WR, Wang LL, et al. Influence of Tongxinluo on C-reactive Protein in patients with diabetes after percutaneous coronary intervention

[ Journal of Chinese Physician 2008;10(10):1392–4.

].[ Chinese Remedies & Clinics 2006;6(3):229–30.

Liu 2009 {published data only} Liu SJ. The effect of Tongxinluo on perioperative CRP patients with ACS

Lu 2012 {published data only} Lu Y, Zhao XJ, Liao XC. The effect of Tongxinluo capsules on the change of hemorheology in patients

Wang 2009c {published data only} Wang X, Li J. Clinical observation for Tongxinluo in the treatment of CHD

PCI

]. Chinese [ Journal of Modern Drug Application 2009;22(3):105–6.

]. Inner Mongol Journal of Traditional Chinese Medicine 2012;14(4):1–2.

Wang 2012 {published data only} Wang L, Liu H, Hu YC. The effect of drug intervention on vascular inflammatory reaction and vascular endothelial function after percutaneous coronary intervention

Ma 2009 {published data only} Ma QL, Zhang SD, Ning YG, Pu XQ, Yu LG, Zheng SF, et al. Effect of Tongxinluo on endothelial function and hypersensitiveC-reactive protein in acute coronary syndrome patients undergoing percutaneous coronary intervention [ Journal of Central South University (Medical Sciences) 2009; 34(06):550–4. Qu 2011 {published data only} Qu JQ, Ma JE, Bai RL. Clinical observation of Tongxinluo in treating patients with CHD

[ China Clinical Practical Medicine 2012;7(18):169–70. ]. Xiao 2004 {published data only} Xiao YQ, Li WK. The effect of Tongxinluo in treating patients with unstable angina pectoris [ medicinae Sinica 2004;17(2):152–3.

]. Chinese and

Su 2000 {published data only} Su XY, Huang JX, Zhao ZJ, Zhao L, Hu YL, Su HR. Clinical observation of 96 cases of variant angina pectoris treated with 96

Wang 2009b {published data only} Wang WY, Liu YB, Sun Y. Effect of Tongxinluo on inflammatory factor in patients with ACS ]. [ Prevention and Treatment of Cardio-cerebral-vascular disease 2009;9(4):308–9.

[ C Journal of New Chinese Medicine 2009;41(7):41–2.

[ Foreign Medical Research 2011;9(12):22.

]. [ Chinese Journal of Primary Medicine and Pharmacy 2007;14 (4):570–1.

[ China Practical Medical 2012;07(13):159–60.

with CHD after PCI [

Wang 2007 {published data only} Wang G. Clinical study Oil Lvedv and Lvef after blood flow reconstruction interfered by Tongxinluo capsule in patients with AMI after percutaneous coronary intervention

Li 2012 {published data only} Li H. The effect of drug intervention on vascular inflammatory reaction and change of vascular endothelial function after percutaneous coronary intervention

Tongxinluo [

PCI

]. Acta

Xu 2007 {published data only} Xu Z, Li X. Influence of Tongxinluo on inflammatory factor of acute coronary syndrome patients after interventional therapy and its early heart complication [ Modern Journal of Integrated Traditional Chinese Western Medicine 2007;16(2):156–7.

Xu 2008 {published data only} Xu LD, Liu LY. The prevention of restenosis after percutaneous coronary intervention [ ]. Practical Cardiocerebral Pulmonary Vascular Disease 2008;16(4):73–6. Yang 2009b {published data only} Yang GK. Inflammatory reaction and change of vascular endothelial function after percutaneous coronary intervention and the effect of drug intervention [ Sichuan Medical Journal 2009;30(11):1788–90. Yang 2010 {published data only} Yang JX, Li MJ, Yang XH. Effect of Tongxinluo on Change of Vascular Inflammation and EndothelialFunction after Percutaneous Coronary Intervention [ Journal of Liaoning University of TCM 2010;12(2):94–6. Yang 2012 {published data only} Yang W, Xu XH, Wang S, Zhang CF. The effect of Tongxinluo on serum P NP and ventricular remodeling in patients with AMI after PCI [

PCI

]. Chinese Journal of Difficult and Complicated Cases 2012;11(6): 452–3. Zhang 2005 {published data only} Zhang W. Effect of Tongxinluo Capsule on Coagulant and Fibrinolysis System andAngiotension II in Patients with CHD after Intracoronary Stenting [ Hebei Medicine 2005;12(1):37–9. Zhang 2006 {published data only} Zhang JW, Yang DC. The protective effects of Tongxinluo on myocardium after reperfusion in PCI patients with acute myocardium infarction [ PCI Medicine Industry Information 2006;3(21):8–10. Zhang 2007 {published data only} Zhang HW. Clinical analysis of integrated traditional and western medicine in treating 62 cases of CHD [ 62 ]. Theory and Practice of Chinese Medicine 2007;17(7):722–3. Zhang 2008 {published data only} Zhang LJ, Li HT, Guo JT, Zhou J. The Effect of Tongxinluo Capsules on the Function of BloodVessel Endothelium (BVE)on the Patientswith Coronary Heart Disease [ Hebei Medicine 2008;14(7):761–7.

Zhang 2009b {published data only} Zhang TX, Zhou JZ. The effect of Tongxinluo on inflammatory cytokins in patients with ACS ]. [ China Journal of Chinese Materia Medica 2009;34(14): 1857–8. Zhang 2010 {published data only} Zhang HT, Jia ZH, Zhang J, Ye ZK, Yang WX, Tian YQ, et al. No-reflow protection and long-term efficacy for acute myocardialinfarction with Tongxinluo: a randomized double-blind placebo-controlled multicenter clinical trial. ]. Chinese Medical Journal 2010;123(20):2858–64. Zhao 2010 {published data only} Zhao H, Tian JH, Hao XY, Ma L. Effects of Tongxinluo on Inflammatory factors in patients with coronary heart disease after percutaneous coronary intervention PCI ]. Acta ]. [ Academiae Mediciane Qindao Universitatis 2010;46(4): 349–351. Zhao 2011 {published data only} Zhao X, Song ZJ, Hou LX. Clinical observation of Tongxinluo in treating patiens after percutaneous coronary intervention [ Information 2011;24(7):173.

]. Medical

References to studies awaiting assessment Deng 2013 {published data only} Deng X. Effect of Tongxinlou capsule on restenosis after PCI in patients with CHD PCI [ China Medicine and Pharmacy 2013;3(12):67–8. II ].

References to ongoing studies Han 2012 {published data only} NCT01721590. Tongxinluo improve high on Clopidogrel platelet reactivity in patients with coronary heart disease. http://clinicaltrials.gov/show/NCT01721590 (accessed November 2012). ].

Additional references Agema 2001 Agema WRP, Jukema JW, Pimstone SN, Kastelein JJP. Genetic aspects of restenosis after percutaneous coronary interventions; towards more tailored therapy. European Heart Journal 2001;22(22):2058–74. Bhattarai 2012 Bhattarai N, Charlton J, Rudisill C, Gulliford MC. Coding, recording and incidence of different forms of coronary heart disease in primary care. PLoS ONE 2012;7(1):e29776. Boissel 1999 ]. Boissel JP, Cucherat M, Li W, Chatellier G, Gueyffier F, Buyse M, et al. The problem of therapeutic efficacy indices.

3. Comparison of the indices and their use. Therapie 1999; 54(4):405–11. Chen 1985 Chen CY. Effect of Scolopendra extraction in the experiment of rabbit heart. Chinese Medicine Pharmacology and Clinical Practice 1985;1(1):124–5. Chen 2007 Chen ZQ, Lai YY, Hong L, Wang H, Qiu Y, Yin QL, et al. The effects of Tongxinluo capsule on platelet activity and vascular endothelium function in patients with ACS after PCI. Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2007;9(7):460–3. Cutlip 2007 Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, van Es GA. Clinical end points in coronary stent trials: a case for standardized definitions. Circulation 2007;115(17): 2344–51. Dangas 1996 Dangas G, Fuster V. Management of restenosis after coronary intervention. American Heart Journal 1996;132(2 Pt 1):428–36. Deeks 2000 Deeks JJ. Issues in the selection of a summary statistic for meta-analyses of binary data. Abstracts of 8th International Cochrane Colloquium. Cape Town: The Cochrane Collaboration, Oct 25–28th, 2000. Dörffler 2005 Dörffler-Melly J, Koopman MM, Prins MH, Büller HR. Antiplatelet and anticoagulant drugs for prevention of restenosis/reocclusion following peripheral endovascular treatment. Cochrane Database of Systematic Reviews 2005, Issue 1. [DOI: 10.1002/14651858.CD002071.pub2] Egger 1997 Egger M, Davey-Smith G, Schneider M, Minder CSO. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;13(7109):629–34. Fattori 2003 Fattori R, Piva T. Drug-eluting stents in vascular intervention. Lancet 2003;361(9353):247–9. Giglioli 2009 Giglioli C, Valente S, Margheri M, Comeglio M, Chiostri M, Romano SM, et al. An angiographic evaluation of restenosis rate at a six-month follow-up of patients with ST-elevation myocardial infarction submitted to primary percutaneous coronary intervention. Internation Journal of Cardiology 2009;131(3):362–9. Go 2014 Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, et al. Heart Disease and Stroke Statistics - 2014 Update. A report from the American Health Association. Circulation 2014;129(3):e28–e292. Grech 2003 Grech ED. ABC of interventional cardiology: percutaneous coronary intervention II: the procedure. BMJ 2003;326 (24):1137–40.

Higgins 2011 Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions 5.0.2 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane–handbook.org. Huntington 2003 Huntington JA, Baglin TB. Targeting thrombin rational drug design from natural mechanisms. Trends in Pharmacological Sciences 2003;24(11):589–95. Kang 2012 Kang Y, Lao H, Yu X, Chen J, Zhong S. Progress in genetic and epigenetic research on in-stent restenosis after percutaneous coronary interventions. Chinese Journal of Medical Genetics 2012;29(1):38–42. Lau 1997 Lau J, Ioannidis JP, Schmid CH. Quantitative synthesis in systematic reviews. Annals of Internal Medicine 1997;127 (9):820–6. Lonn 2010 Lonn E, Bosch J, Teo KK, Pais P, Xavier D, Yusuf S. The polypill in the prevention of cardiovascular diseases: key concepts, current status, challenges, and future directions. Circulation 2010;122(20):2078–88. Lozano 2012 Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010. Lancet 2012;380(9859):2095–128. Lu 2006 Lu XY, Shi DZ, Xu H. Clinical study on effect of Xiongshao capsule on restenosis after percutaneous coronary intervention. Zhongguo Zhong Xi Yi Jie He Za Zhi 2006;26 (1):13–7. Modi 1995 Modi NB, Baughman SA, Paasch BD. Pharmaco*kinetics and pharmacodynamics of TP-9201, a GPIIbIIIa antagonist, in rats and dogs. Journal of Cardiovascular Pharmacology 1995; 25(6):888. NHLBI 2011 National Heart Lung and Blood Institute (NHLBI). Health Topic: Coronary heart disease. Available from http:// www.nhlbi.nih.gov/health/health-topics/topics/cad/ 2011. Nong 1989 Nong ZJ, Shen YY, Dong HC. The effect of Eupolyphaga Sinensis Walk alkaloids on rabbits cardial pump function. Journal of Anhui Traditional Chinese Medical College 1989;8 (3):84–6. Nong 2000 Nong MZ. Research on combined treatment of unstable angina pectoris with TCM and WM. Zhong Yi Han Shou Tong Xun 2000;19(4):51–2. Odell 2006 Odell A, Grip L, Hallberg LR. Restenosis after percutaneous coronary intervention (PCI): experiences from the patients’

perspective. European Journal of Cardiovascular Nursing 2006;5(2):150–7. Paul 1994 Johnson PH. Hirudin: Clinical potential of a thrombin inhibitor. Annual Review of Medicine 1994;45:165–77. Pei 1986 Pei YQ, Wen SR, Wang XY, Huo SP, Wei MC. Study of cardiac stimulation of Ginsenoside of upper part over grand. Journal of Beijing Medical University 1986;18(2):140–1. Pereira 2012 Pereira TV, Horwitz RI, Ioannidis JP. Empirical evaluation of very large treatment effects of medical interventions. JAMA 2012;308(14):1676–84. Rajaqopal 2003 Rajaqopal V, Rockson SG. A review of mechanisms and management. American Journal of Medicine 2003;115(7): 547–53. RevMan 2008 [Computer program] The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.1. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2008. Richard 2002 Holubkov R, Laskey WK, Haviland A, Slater JC, Bourassa MG, Vlachos HA, et al. Angina 1 year after percutaneous coronary intervention: a report from the NHLBI Dynamic Registry. American Heart Journal 2002 Nov;144(5):826–33. Rosanio 1999 Rosanio S, Tocchi M, Patterson C, Runge MS. Prevention of restenosis after percutaneous coronary interventions: the medical approach. Journal of Thrombosis and Haemostasis 1999;82 Suppl 1:164–70. Ruan 2003 Ruan JL, Zhao ZX, Zeng QZ, Qian ZM. Recent advances in study of component and pharmacological roles of Radix Paeoniae Rubra. Chinese Pharmacological Bulletin 2003;19 (9):965–70. Serruys 1995 Serruys PW, Herrman JP, Simon R, Rutsch W, Bode C, Laarman GJ, et al. A comparison of hirudin with heparin in the prevention of restenosis after coronary angioplasty. The New England Journal of Medicine 1995;333(12):757–63. Singh 2011 Singh IM, Holmes DR Jr. Myocardial revascularization by percutaneous coronary intervention: past, present, and the future. Current Problems in Cardiology 2011;36(10): 375–401.

percutaneous coronary intervention: a meta-analysis of troponin elevation applying the new universal definition. QJM 2009;102(6):369–78. Wang 2003 Wang HJ, Huang YW, Sun J, Zhu CH, Zhang L. Effect of Tongxinluo capsule on function of vascular endotheliumin patients with unstable angina pectoris. Chinese Journal of Integrated Traditional Chinese and Western Medicine 2003; 23(8):587–9. Wang 2007 Wang G, Mao B, Xiong ZY, Fan T, Chen XD, Wang L, et al. The quality of reporting of randomized controlled trials of traditional Chinese medicine: a survey of 13 randomly selected journals from mainland China. Clinical Therapeutics 2007;29(7):1456–67. Wang 2008 Wang CH, Wang R, Cheng XM, He YQ, Wang ZT, Wu C, et al. Comparative pharmaco*kinetic study of paeoniflorin after oral administration of decoction of Radix Paeoniae Rubra and Radix Paeoniae Alba in rats. Journal of Ethnopharmacology 2008;117(3):467–72. WHO 2002 World Health Organization. Life course perspectives on coronary heart disease, stroke and diabetes. Department of Noncommunicable Disease Prevention and Health Promotion. Noncommunicable Disease and Mental Health Cluster 2002. WHO 2011 World Health Organization. Health topic: cardiovascular diseases (CVDs). Available from http://www.who.int/ mediacentre/factsheets/fs317/en/index.html 2011. WHS 2010 World Health Statistics. Cause-specific mortality and morbidity. Available at: http://www.who.int/whosis/ whostat/EN˙WHS09˙Table2.pdf 2010. Wu 2001 Wu YL. Luobing theory of Chinese medicine and cardiocerebral antipathy. 1st Edition. Beijing: Chinese Science and Technical Publish House, 2001. Wu 2006 Wu T, Harrison RA, Chen XY, Ni J, Zhou L, Qiao J, et al. Tongxinluo (Tong xin luo or Tong-xin-luo) capsule for unstable angina pectoris. Cochrane Database of Systematic Reviews 2006, Issue 4. [DOI: 10.1002/ 14651858.CD004474.pub2]

Sterne 2001 Sterne JA, Egger M. Funnel plots for detecting bias in metaanalysis: guidelines on choice of axis. Journal of Clinical Epidemiology 2001;54(10):1046–55.

Wu 2013 Wu XY, Tang JL, Mao C, Yuan JQ, Qin Y, Chung VC. Systematic reviews and meta-analyses of traditional Chinese medicine must search Chinese databases to reduce language bias. Evidence Based Complementary and Alternative Medicine 2013:812179.

Testa 2009 Testa L, Van Gaal WJ, Biondi Zoccai GG, Agostoni P, Latini RA, Bedogni F, et al. Myocardial infarction after

Xu 1988 Xu YJ. Effect of inhibition platelet adhesion reaction of Radix Ginseng. Journal of Pharmacology 1988;23(5):284–5.

Yu 2011 Yu M, Huang YN, Mo W. Progress and prospect of Hirudin and Its derivants research. Pharmaceutical Biotechnology 2011;18(4):351–4. Zhang 2004 Zhang Q, Yang LH, Qiao P, Cui TX. Effects of tongxinluo capsule in the treatment of 68 patients with unstable angina pectoris. Chinese Journal of Primary Medicine and Pharmacy 2004;11(9):1080–1. Zheng 1998 Zheng HZ, Dong ZH, Se J. Periostracum Cicadae. Modern Study of Traditional Chinese Medicine. 1st Edition. Beijing: Xue Yuan Press, 1998:5137–45. Zhou 1997 Zhou JK, Liu C. Thrombin inhibitor-hirudin. Chinese New Drugs Journal 1997;6(3):186–7. Zhou 2007 a Zhou J, Guo JT. Clinical study of Tongxinluo on preventing

re-stenosis of stents in CHD. Hebei Medicine 2007;13(10): 1188–91. Zhou 2011 Zhou ZR, Tang HQ, Li JH, Yang LL, Hu H. Tongxinluo capsule for coronary heart disease: a systematic review. Chinese Journal Of Evidence-Based Medicine 2011;11(9): 1078–83. Zhu 2004 Zhu QL. Study on Tongxinluo capsule in preventing and treating coronary restenosis after PTCA. Journal of Shandong University of Traditional Chinese Medicine 2004:CNKI:CDMD:2.2004.102498. Zhuo 2008 Zhuo Q, Yang X, Wu T, Liu G, Zhou L. Tongxinluo capsule for acute stroke. Cochrane Database of Systematic Reviews 2008, Issue 4. [DOI: 10.1002/ 14651858.CD004584.pub2] ∗ Indicates the major publication for the study

CHARACTERISTICS OF STUDIES Characteristics of included studies [ordered by study ID] Chen 2011 Methods

Study design: randomised controlled trial. Method of randomisation: random number table. Concealment of allocation: no description. Exclusions post randomisation: none. Length of follow-up: 6 months. Losses to follow-up: none. Intention-to-treat analysis: not mentioned.

Participants

Patients were all diagnosed as having ACS based on coronary arteriography, and in accordance with the diagnostic criteria formulated by the European Society of Cardiology in September 2000 Tong-xin-luo group: 80 patients (male/female: 48/32; age: 71.5 ± 5.6 years) Control group: 80 patients (male/female: 46/34; age: 70.7 ± 5.8 years)

Interventions

Control: conventional treatment (pre-operation: aspirin 100 mg qd, clopidogrel 75 mg qd; post-operation: aspirin, clopidogrel, nitroglycerin, low molecular weight heparin, ACEI, atorvastatin) Tong-xin-luo group: conventional treatment plus Tong-xin-luo capsules (4 capsules tid; 0.26 g/capsule). Duration of intervention: 6 months.

Outcomes

Occurrence of angiographic restenosis; Occurrence of heart failure and angina.

Notes Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Low risk bias)

Randomised, random number table was used.

Allocation concealment (selection bias)

No description about the allocation procedure.

Unclear risk

Blinding of participants and personnel High risk (performance bias) All outcomes

No description about blinding. No placebo.

Blinding of outcome assessment (detection High risk bias) All outcomes

No description about blinding. No placebo.

Chen 2011

(Continued)

Incomplete outcome data (attrition bias) Angiographic restenosis

Low risk

Same numbers of participants randomly assigned and analysed. No missing outcome data

Incomplete outcome data (attrition bias) Low risk Outcomes other than angiographic restenosis

Same numbers of participants randomly assigned and analysed. No missing outcome data

Selective reporting (reporting bias)

Unclear risk

The study protocol is not available.

Other bias

Low risk

Baseline characteristics (sex, age, type of angina, disease severity, disease duration, comorbidities, blood glucose, blood pressure, serum lipoid, etc.) were comparable between the two groups (P > 0.05). The study appeared to be free of other sources of bias

Dai 2011 Methods

Participants

Included participants were 45 to 74 years old, all diagnosed as CHD based on coronary arteriography, and successfully underwent PCI operation Tong-xin-luo group: 31 participants (male/female: 19/12; age: 61.3 ± 7.23 years) Control group: 30 participants (male/female: 17/13; age: 63.5 ± 6.1 years)

Interventions

Control: conventional treatment (aspirin 100 mg qd, clopidogrel 75 mg qd, atorvastatin 20 mg qn; other symptomatic treatment was applied according to illness state) Tong-xin-luo group: conventional treatment plus Tong-xin-luo capsules. Duration of intervention: 6 months.

Outcomes

Occurrence of angiographic restenosis.

Notes Risk of bias Bias

Authors’ judgement

Support for judgement

Dai 2011

(Continued)

Random sequence generation (selection Unclear risk bias)

Randomised, but detailed information on the randomisation method was not provided

Allocation concealment (selection bias)

No description about the allocation procedure.

Unclear risk

Blinding of participants and personnel High risk (performance bias) All outcomes

No description about blinding. No placebo.

Blinding of outcome assessment (detection High risk bias) All outcomes

No description about blinding. No placebo.

Incomplete outcome data (attrition bias) Angiographic restenosis

No missing outcome data.

Unclear risk

Incomplete outcome data (attrition bias) Unclear risk Outcomes other than angiographic restenosis

Outcomes were not reported.

Selective reporting (reporting bias)

Unclear risk

The study protocol is not available.

Other bias

Low risk

Baseline information showed no statistical differences in sex, age, disease duration and type of PCI operation between two groups (P > 0.05). The study appeared to be free of other sources of bias

Di 2012 Methods

Participants

Included participants were over 18 years of age, with evidence of coronary arteriography showing stenosis of more than 70% deduction in small vessels Tong-xin-luo group: 25 participants (male/female: 18/7; age: 64.60 ± 8.69 years) Control group: 25 participants (male/female: 16/9; age: 63.04 ± 7.84 years)

Interventions

Control: conventional treatment (aspirin 100 mg qd, clopidogrel 75 mg qd, atorvastatin 10-20 mg qd) Tong-xin-luo group: conventional treatment plus Tong-xin-luo capsules (3 capsules tid;

Di 2012

(Continued)

0.38 g/capsule). Duration of intervention: 6-12 months. Co-intervention: none. Outcomes

Occurrence of myocardial infarction and angina; All cause mortality; Use of revascularisation, including PCI and coronary artery bypass graft surgery

Notes Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Unclear risk bias)

Randomised, but detailed information on the randomisation method was not provided

Allocation concealment (selection bias)

No description about the allocation procedure.

Unclear risk

Blinding of participants and personnel High risk (performance bias) All outcomes

No description about blinding. No placebo.

Blinding of outcome assessment (detection High risk bias) All outcomes

No description about blinding. No placebo.

Incomplete outcome data (attrition bias) Angiographic restenosis

The outcome was not reported.

Unclear risk

Incomplete outcome data (attrition bias) Low risk Outcomes other than angiographic restenosis

There was no loss to follow-up.

Selective reporting (reporting bias)

Unclear risk

The study protocol is not available.

Other bias

Low risk

Baseline information between groups showed no statistical differences in sex, age, smoking history, history of disease, types of CHD, levels of blood glucose and levels of blood lipoid (P > 0.05). The study appeared to be free of other sources of bias

Dong 2012 Methods

Participants

Participants were those who underwent emergency PCI within 6 hours of AMI Tong-xin-luo group: 35 participants (male/female: 21/14; age: 61.20 ± 11.47 years) Control group: 28 participants (male/female: 15/13; age: 58.80 ± 8.96 years)

Interventions

Control group: conventional treatment (low molecular weight heparin 5000 IU subcutaneous injection bid for 3 days; aspirin 100 mg qd, clopidogrel 75 mg qd, ACEI, nitroglycerin, etc) Tong-xin-luo group: conventional treatment plus Tong-xin-luo capsules (4 capsules tid) . Duration of intervention: 12 months.

Outcomes

Occurrence of myocardial infarction; Mortality (death) due to any cardiovascular event.

Notes Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Unclear risk bias)

Randomised, but detailed information on the randomisation method was not provided

Allocation concealment (selection bias)

No description about the allocation procedure.

Unclear risk

Blinding of participants and personnel High risk (performance bias) All outcomes

No description about blinding. No placebo.

Blinding of outcome assessment (detection High risk bias) All outcomes

No description about blinding. No placebo.

Incomplete outcome data (attrition bias) Angiographic restenosis

The outcome was not reported.

Unclear risk

Incomplete outcome data (attrition bias) Low risk Outcomes other than angiographic restenosis

There was no loss to follow-up.

Dong 2012

(Continued)

Selective reporting (reporting bias)

Low risk

The study protocol is not available, but study reported same outcomes as described in the methods

Other bias

Low risk

Baseline information between groups showed no statistical differences in sex, age, smoking, comorbidities, number of stents and length of lesion between two groups (P > 0.05). The study appears to be free of other sources of bias

Huang 2010 Methods

Participants

Participants were diagnosed as acute ST segment elevation myocardial infarction based on the Acute Myocardial Infarction Diagnosis and Treatment Guidelines formulated by the Chinese Society of Cardiology of the Chinese Medical Doctors Associations in 2001, and received PCI within 12 hours after occurrence of AMI. There were 62 patients in the Tong-xin-luo group, and 58 in the control group male/female: 68/52; age: 58.3 ± 12.6 years.

Interventions

Control group: conventional treatment (low molecular weight heparin, aspirin 100 mg qd, clopidogrel 75 mg qd) Tong-xin-luo group: conventional treatment + Tong-xin-luo capsules (4 capsules, tid). Duration of intervention: 6 months.

Outcomes

Occurrence of myocardial infarction; Mortality (death) due to any cardiovascular event; Use of revascularisation.

Notes Risk of bias Bias

Authors’ judgement

Random sequence generation (selection Unclear risk bias)

Support for judgement Randomised, but detailed information on the randomisation method was not provided

Huang 2010

(Continued)

Allocation concealment (selection bias)

Unclear risk

No description about the allocation procedure.

Blinding of participants and personnel High risk (performance bias) All outcomes

No description about blinding. No placebo.

Blinding of outcome assessment (detection High risk bias) All outcomes

No description about blinding. No placebo.

Incomplete outcome data (attrition bias) Angiographic restenosis

The outcome was not reported.

Unclear risk

Incomplete outcome data (attrition bias) Low risk Outcomes other than angiographic restenosis

Same numbers of participants randomly assigned and analysed. No missing outcome data

Selective reporting (reporting bias)

Unclear risk

The study protocol is not available.

Other bias

Low risk

Baseline information showed no statistical differences in sex, age, smoking, drinking habits, comorbidities, Killip’s cardiac functional classification, number and distributions of coronary pathological changes, blood pressure, levels of blood glucose and levels of blood lipoid between the two groups (P > 0.05). The study appeared to be free of other sources of bias

Li 2004 Methods

Participants

Participants were those who underwent PTCA and stenting successfully Tong-xin-luo group: 38 participants (age: 56.6 ± 11.2 years) Control group: 38 participants (age: 54.9 ± 11.8 years).

Interventions

Conventional treatment: • Pre-operation (from 3 days before operation): aspirin 300 mg qd, clopidogrel 250 mg bid • Intra-operation: heparin 10000 IU, then 1000 IU/hour during operation

Li 2004

(Continued)

• Post-operation: aspirin 300 mg qd, then reduced to 100 mg qd after 2 weeks; clopidogrel 250 mg bid, reduced to 250 mg qd after 4 weeks and applied for 3 months. ACEI, nitroglycerin and statin, were selectively applied Tong-xin-luo group: conventional treatment plus Tong-xin-luo capsules (4 capsules, tid) . Control: conventional treatment. Duration of intervention: 6 months. Co-intervention: none. Outcomes

Occurrence of myocardial infarction and angina.

Notes Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Unclear risk bias)

Randomised, but detailed information on the randomisation method was not provided

Allocation concealment (selection bias)

No description about the allocation procedure.

Unclear risk

Blinding of participants and personnel High risk (performance bias) All outcomes

No description about blinding. No placebo.

Blinding of outcome assessment (detection High risk bias) All outcomes

No description about blinding. No placebo.

Incomplete outcome data (attrition bias) Angiographic restenosis

The outcome was not reported.

Unclear risk

Incomplete outcome data (attrition bias) Low risk Outcomes other than angiographic restenosis

There was no loss to follow-up.

Selective reporting (reporting bias)

Unclear risk

The study protocol is not available.

Other bias

Low risk

Baseline information between groups showed no statistical differences in age, number of stents implanted, types of CHD and distributions of coronary pathological changes between the two groups (P > 0.05) . The study appeared to be free of other sources of bias

Liang 2010 Methods

Participants

Participants were patients with AMI, with evidence of coronary arteriography showing stenosis ≥ 70%, who successfully received stent implantations. There were 42 patients in Tong-xin-luo group, and 38 in control group male/female: 52/28; mean age: 55 years (ranging from 40 to 70)

Interventions

Control group: conventional treatment (low molecular weight heparin, aspirin, clopidogrel, beta-blockers, nitrates, statin) Tong-xin-luo group: conventional treatment plus Tong-xin-luo capsules (0.52 g, tid). Duration of intervention: 6 months. Co-intervention: none.

Outcomes

Occurrence of angiographic restenosis; Occurrence of myocardial infarction and angina.

Notes Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Unclear risk bias)

Randomised, but detailed information on the randomisation method was not provided

Allocation concealment (selection bias)

No description about the allocation procedure.

Unclear risk

Blinding of participants and personnel High risk (performance bias) All outcomes

No description about blinding. No placebo.

Blinding of outcome assessment (detection High risk bias) All outcomes

No description about blinding. No placebo.

Incomplete outcome data (attrition bias) Angiographic restenosis

Whether all participants were brought back for angiography was not reported

Unclear risk

Incomplete outcome data (attrition bias) Low risk Outcomes other than angiographic restenosis

There was no loss to follow-up.

Liang 2010

(Continued)

Selective reporting (reporting bias)

Unclear risk

The study protocol is not available.

Other bias

Unclear risk

Insufficient information to assess whether potential risk of other bias existed

Wang 2009a Methods

Study design: randomised controlled trial. Method of randomisation: no description. Concealment of allocation: no description. Exclusions post randomisation: none. Losses to follow-up: none. Intention-to-treat analysis: not mentioned.

Participants

Participants were those who underwent PCI successfully (residual stenosis < 20%), aging from 35 to 74 Tong-xin-luo group: 40 participants (male/female: 28/12; age: 54.2 ± 10.2 years) Control group: 40 participants (male/female: 26/14; age: 52.5 ± 11 years)

Interventions

Control group: Conventional treatment (low molecular weight heparin 6000 IU subcutaneous injection bid for 5 days; aspirin 100 mg qd, clopidogrel 75 mg qd) Tong-xin-luo group: conventional treatment plus Tong-xin-luo capsules (3 capsules, tid; 0.38 g/capsule). Duration of intervention: 6 months. Co-intervention: none.

Outcomes

Occurrence of myocardial infarction and angina.

Notes Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Unclear risk bias)

Randomised, but detailed information on the randomisation method was not provided

Allocation concealment (selection bias)

No description about the allocation procedure.

Unclear risk

Blinding of participants and personnel High risk (performance bias) All outcomes

No description about blinding. No placebo.

Blinding of outcome assessment (detection High risk bias) All outcomes

No description about blinding. No placebo.

Wang 2009a

(Continued)

Incomplete outcome data (attrition bias) Angiographic restenosis

Unclear risk

The outcome was not reported.

Incomplete outcome data (attrition bias) Low risk Outcomes other than angiographic restenosis

There was no loss to follow-up.

Selective reporting (reporting bias)

Unclear risk

The study protocol is not available.

Other bias

Low risk

Baseline information showed no statistical differences in sex, age, smoking, comorbidities, length of lesion and distributions of coronary pathological changes between the two groups (P > 0.05). The study appeared to be free of other sources of bias

Wang 2010 Methods

Study design: randomised, double-blind, parallel, placebo-controlled trial. Method of randomisation: no description. Concealment of allocation: no description. Exclusions post randomisation: none. Length of follow-up: 12 months. Losses to follow-up: none. Intention-to-treat analysis: not mentioned.

Participants

Participants were diagnosed as having type II diabetes mellitus based on oral glucose tolerance test, and had evidence of coronary arteriography showing stenosis of no less than 70% reduction in small vessels with length of lesions no less than 3 mm Tong-xin-luo group: 68 participants (male/female: 43/25; age: 65.2 ± 9.9 years) Control group: 64 participants (male/female: 45/19; age: 65.1 ± 10.4 years)

Interventions

Control group: conventional treatment (aspirin 300 mg qd, and reduced to 100 mg qd after a month; clopidogrel 75 mg qd; atorvastatin 20 mg qn) + placebo Tong-xin-luo group: conventional treatment + Tong-xin-luo capsules (3 capsules, tid; 0. 38 g/capsule). Duration of intervention: 12 months.

Outcomes

Occurrence of myocardial infarction and angina; All cause mortality.

Notes Risk of bias Bias

Authors’ judgement

Support for judgement

Wang 2010

(Continued)

Random sequence generation (selection Unclear risk bias)

Randomised, but detailed information on the randomisation method was not provided

Allocation concealment (selection bias)

Unclear risk

No description about the allocation procedure.

Blinding of participants and personnel Unclear risk (performance bias) All outcomes

No description about blinding. No placebo.

Blinding of outcome assessment (detection Unclear risk bias) All outcomes

No description about blinding. No placebo.

Incomplete outcome data (attrition bias) Angiographic restenosis

The outcome was not reported.

Unclear risk

Incomplete outcome data (attrition bias) Low risk Outcomes other than angiographic restenosis

There was no loss to follow-up.

Selective reporting (reporting bias)

Unclear risk

The study protocol is not available.

Other bias

Low risk

Baseline information showed no statistical differences in sex, age, smoking, comorbidities, number and length of stents implanted, number and distributions of coronary pathological changes and level of serum creatinine between the two groups (P > 0.05). The study appeared to be free of other sources of bias

Wu 2010 Methods

Participants

Participants were patients with unstable angina based on the Unstable Angina Diagnosis and Treatment Guidelines formulated by the Chinese Society of Cardiology of the Chinese Medical Doctors Associations in 2007, and underwent PCI successfully Tong-xin-luo group: 57 patients (male/female: 32/25; age: 71.4 ± 4.5 years) Control group: 53 patients (male/female: 31/22; age: 69.8 ± 4.3 years)

Wu 2010

(Continued)

Interventions

Control: conventional treatment: • Pre-operation: aspirin 100 mg qd, clopidogrel 75 mg qd for more than 7 days. • Post-operation: aspirin, clopidogrel, nitroglycerin, low molecular weight heparin, ACEI, etc Tong-xin-luo group: conventional treatment plus Tong-xin-luo capsules (4 capsules, tid; 0.38 g/capsule) Duration of intervention: 6 months. Co-intervention: none.

Outcomes

Occurrence of angiographic restenosis; Occurrence of myocardial infarction, heart failure and angina; Use of revascularisation, including PCI and coronary artery bypass graft surgery

Notes Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Unclear risk bias)

Randomised, but detailed information on the randomisation method was not provided

Allocation concealment (selection bias)

No description about the allocation procedure.

Unclear risk

Blinding of participants and personnel High risk (performance bias) All outcomes

No description about blinding. No placebo.

Blinding of outcome assessment (detection High risk bias) All outcomes

No description about blinding. No placebo.

Incomplete outcome data (attrition bias) Angiographic restenosis

Whether all participants were brought back for angiography was not reported

Unclear risk

Incomplete outcome data (attrition bias) Low risk Outcomes other than angiographic restenosis

There was no loss to follow-up.

Selective reporting (reporting bias)

Unclear risk

The study protocol is not available.

Other bias

Low risk

Baseline information showed no statistical differences in sex, age, comorbidities, number and distributions of coronary pathological changes, blood pressure, levels of blood glucose and levels of blood lipoid between the two groups (P > 0.05). The study ap-

Wu 2010

(Continued)

peared to be free of other sources of bias

Xiao 2007 Methods

Study design: randomised controlled trial. Method of randomisation: no description. Concealment of allocation: no description. Exclusions post randomisation: none. Length of follow-up: 6 months. Losses to follow-up: 37 of 62 participants in Tong-xin-luo group and 47 of 70 participants in control group did not undergo coronary arteriography, the occurrence of angiography restenosis for these participants was lost to follow-up. Intention-to-treat analysis: not mentioned.

Participants

Participants were those who successfully received bare-metal coronary stents Tong-xin-luo group: 62 participants (male/female: 42/20; age: 53 ± 12 years) Control group: 70 participants (male/female: 49/21; age: 55 ± 10 years)

Interventions

Tong-xin-luo group: conventional treatment plus Tong-xin-luo capsules (4 capsules, tid) Control group: Conventional treatment. Duration of intervention: 6 months. Co-intervention: none.

Outcomes

Occurrence of angiographic restenosis; Occurrence of myocardial infarction, heart failure, and angina; Mortality (death) due to any cardiovascular event.

Notes

There were no losses to follow-up in the outcomes measured, except angiographic restenosis

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Unclear risk bias)

Randomised, but detailed information on the randomisation method was not provided

Allocation concealment (selection bias)

No description about the allocation procedure.

Unclear risk

Blinding of participants and personnel High risk (performance bias) All outcomes

No description about blinding. No placebo.

Blinding of outcome assessment (detection High risk bias) All outcomes

No description about blinding. No placebo.

Xiao 2007

(Continued)

Incomplete outcome data (attrition bias) Angiographic restenosis

High risk

37 of 62 participants in Tong-xin-luo group and 47 of 70 participants in control group did not undergo coronary arteriography

Incomplete outcome data (attrition bias) Low risk Outcomes other than angiographic restenosis

There was no loss to follow-up.

Selective reporting (reporting bias)

Unclear risk

The study protocol is not available.

Other bias

Low risk

Baseline information showed no statistical differences in sex, age, comorbidities, types of coronary pathological changes and average number of stents between the two groups (P > 0.05). The study appeared to be free of other sources of bias

Yang 2009a Methods

Study design: randomised controlled trial. Method of randomisation: random number table. Concealment of allocation: no description. Exclusions post randomisation: none. Length of follow-up: 3 months. Losses to follow-up: none. Intention-to-treat analysis: not mentioned.

Participants

Participants were diagnosed as having AMI based on the Acute Myocardial Infarction Diagnosis and Treatment Guidelines formulated by the Chinese Society of Cardiology of the Chinese Medical Doctors Associations in 2001, who successfully underwent PCI Tong-xin-luo group: 30 participants (male/female: 22/8; age mean: 58 years) Control group: 29 participants (male/female: 25/4; age mean: 56 years )

Interventions

Control group: conventional treatment: • Pre-operation: aspirin 300 mg qd, clopidogrel 600 mg qd. • Intra-operation: heparin 1000 IU/kg, then 1000 IU/hour during operation. • Post-operation: low molecular weight heparin 5000 IU subcutaneous injection bid for 7 days; aspirin 300 mg qd Tong-xin-luo group: conventional treatment plus Tong-xin-luo capsules (3 capsules, tid) . Duration of intervention: more than 24 months. Co-intervention: none.

Outcomes

Occurrence of myocardial infarction and heart failure; Mortality (death) due to any cardiovascular event; All cause mortality; Use of revascularisation.

Yang 2009a

(Continued)

Notes

Withdrawal of one participant before randomisation was reported

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Low risk bias)

Randomised, random number table was used as randomisation method

Allocation concealment (selection bias)

No description about the allocation procedure.

Unclear risk

Blinding of participants and personnel High risk (performance bias) All outcomes

No description about blinding. No placebo.

Blinding of outcome assessment (detection High risk bias) All outcomes

No description about blinding. No placebo.

Incomplete outcome data (attrition bias) Angiographic restenosis

The outcome was not reported.

Unclear risk

Incomplete outcome data (attrition bias) Low risk Outcomes other than angiographic restenosis

Same numbers of participants randomly assigned and analysed. No missing outcome data

Selective reporting (reporting bias)

High risk

The study protocol is not available, but some outcomes of interest described in the methods were not reported

Other bias

Low risk

Baseline information showed no statistical differences in sex, age, comorbidities, numbers of coronary pathological changes and classification of the New York Heart Function Assessment between the two groups (P > 0.05). The study appeared to be free of other sources of bias

Yao 2006 Methods

Participants

Participants were patients with CHD, with evidence of coronary arteriography showing stenosis ≥ 70%, who successfully received stenting Tong-xin-luo group: 38 participants (age: 56.6 ± 10.9 years) Control group: 38 participants (age: 50.1 ± 12.4 years ).

Interventions

Control group: conventional treatment: • Pre-operation(3 days before operation): aspirin 300 mg qd, clopidogrel 75 mg qd, simvastatin 20 mg qd. • Intra-operation: heparin 10000 IU/kg, then 1000 IU/hour during operation. • Post-operation: low molecular weight heparin 600 ml subcutaneous injection bid for 5 days; aspirin 300 mg qd, clopidogrel 75 mg qd Tong-xin-luo group: conventional treatment plus Tong-xin-luo capsules (4 capsules, tid) . Duration of intervention: 6 months. Co-intervention: none.

Outcomes

Occurrence of angina.

Notes Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Unclear risk bias)

Randomised, but detailed information on the randomisation method was not provided

Allocation concealment (selection bias)

No description about the allocation procedure.

Unclear risk

Blinding of participants and personnel High risk (performance bias) All outcomes

No description about blinding. No placebo.

Blinding of outcome assessment (detection High risk bias) All outcomes

No description about blinding. No placebo.

Incomplete outcome data (attrition bias) Angiographic restenosis

The outcome was not reported.

Unclear risk

Yao 2006

(Continued)

Incomplete outcome data (attrition bias) Low risk Outcomes other than angiographic restenosis

There was no loss to follow-up.

Selective reporting (reporting bias)

Unclear risk

The study protocol is not available.

Other bias

Low risk

Baseline information between groups showed no statistical differences in sex, age, length of lesions, distributions of coronary pathological changes and severity of stenosis between the two groups (P > 0.05). The study appears to be free of other sources of bias

Zhang 2009a Methods

Study design: randomised controlled trial. Method of randomisation: drawing of lots. Concealment of allocation: no description. Exclusions post randomisation: none. Length of follow-up: 3-48 months. Losses to follow-up: none. Intention-to-treat analysis: not mentioned.

Participants

Participants were diagnosed as having AMI based on the diagnostic criteria formulated by the European Society of Cardiology in September, 2000, and underwent PCI successfully Tong-xin-luo group: 96 participants (male/female: 70/26; age: 60 ± 5 years) Control group: 82 participants (male/female: 57/25; age: 58 ± 8 years)

Interventions

Conventional treatment: • Pre-operation: aspirin 100-300 mg, clopidogrel 600 mg. • Post-operation:aspirin 100 mg qd; clopidogrel 75 mg qd for 9-12 months, other symptomatic treatment (ACEI, nitroglycerin, etc.) was applied according to illness state Tong-xin-luo group: conventional treatment plus Tong-xin-luo capsules (3 capsules, tid) . Duration of intervention: more than 24 months. Co-intervention: none.

Outcomes

Occurrence of myocardial infarction, angina and heart failure; Mortality (death) due to any cardiovascular event; All cause mortality; Use of revascularisation.

Notes Risk of bias Bias

Authors’ judgement

Support for judgement

Zhang 2009a

(Continued)

Random sequence generation (selection Low risk bias)

Randomised, drawing of lots was used as randomisation method

Allocation concealment (selection bias)

No description about the allocation procedure.

Unclear risk

Blinding of participants and personnel High risk (performance bias) All outcomes

No description about blinding. No placebo.

Blinding of outcome assessment (detection High risk bias) All outcomes

No description about blinding. No placebo.

Incomplete outcome data (attrition bias) Angiographic restenosis

The outcome was not reported.

Unclear risk

Incomplete outcome data (attrition bias) Low risk Outcomes other than angiographic restenosis

Same numbers of participants randomly assigned and analysed. No missing outcome data

Selective reporting (reporting bias)

Unclear risk

The study protocol is not available.

Other bias

Low risk

Baseline information between groups showed no statistical differences in sex, age, comorbidities, smoking, length of lesions, number of stents, types of stents and number of coronary pathological changes between the two groups (P > 0.05). The study appeared to be free of other sources of bias

Zheng 2010 Methods

Participants

Participants were patients diagnosed as having ACS who underwent emergency PCI 1224 hours after admission Tong-xin-luo group: 34 participants (male/female: 28/6; age: 63 ± 10 years) Control group: 56 participants (male/female: 46/10; age: 61 ± 11 years)

Zheng 2010

(Continued)

Interventions

Control group: conventional treatment (low molecular weight heparin, aspirin, clopidogrel, beta-blockers, nitrates, statin, etc.) Tong-xin-luo group: conventional treatment plus Tong-xin-luo capsules (3 capsules, tid; 0.38 g/capsule). Duration of intervention: 6 months. Co-intervention: none.

Outcomes

Occurrence of myocardial infarction; Use of revascularisation.

Notes Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Unclear risk bias)

Randomised, but detailed information on the randomisation method was not provided

Allocation concealment (selection bias)

No description about the allocation procedure.

Unclear risk

Blinding of participants and personnel High risk (performance bias) All outcomes

No description about blinding. No placebo.

Blinding of outcome assessment (detection High risk bias) All outcomes

No description about blinding. No placebo.

Incomplete outcome data (attrition bias) Angiographic restenosis

The outcome was not reported.

Unclear risk

Incomplete outcome data (attrition bias) Low risk Outcomes other than angiographic restenosis

Same numbers of participants randomly assigned and analysed. No missing outcome data

Selective reporting (reporting bias)

Unclear risk

The study protocol is not available.

Other bias

Unclear risk

Insufficient information to assess whether potential risk of other bias exists

Zhou 2007b Methods

Participants

Participants were patients diagnosed as having CHD based on the World Health Organization diagnostic criteria, who successfully received stent implantations. There were 70 patients in the Tong-xin-luo group, and 66 in the control group male/female: 86/50; mean age: 56.8 years (ranging from 30 to 76)

Interventions

Control group: conventional treatment (low molecular weight heparin, aspirin, clopidogrel, beta-blockers, nitrates, statin, etc.) Tong-xin-luo group: conventional treatment plus Tong-xin-luo capsules (3 capsules, tid) . Duration of intervention: 6 months. Co-intervention: none.

Outcomes

Occurrence of myocardial infarction and angina; Use of revascularisation, including PCI and coronary artery bypass graft surgery

Notes Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Unclear risk bias)

Randomised, but detailed information on the randomisation method was not provided

Allocation concealment (selection bias)

No description about the allocation procedure.

Unclear risk

Blinding of participants and personnel Unclear risk (performance bias) All outcomes

No description about blinding.

Blinding of outcome assessment (detection Unclear risk bias) All outcomes

No description about blinding.

Incomplete outcome data (attrition bias) Angiographic restenosis

Whether all participants were brought back for angiography was not reported

Unclear risk

Incomplete outcome data (attrition bias) Low risk Outcomes other than angiographic restenosis

Same numbers of participants randomly assigned and analysed. No missing outcome data

Zhou 2007b

(Continued)

Selective reporting (reporting bias)

High risk

The study protocol is not available, but some outcomes of interest described in the methods were not reported in results

Other bias

Unclear risk

Insufficient information to assess whether potential risk of other bias exists

Abbreviations ACS: acute coronary syndrome qd: daily ACEI: angiotensin-converting-enzyme inhibitor CHD: coronary heart disease qn: every night PCI: percutaneous coronary intervention tid: three times daily bid: twice daily AMI: acute myocardial infarction PCTA: percutaneous transluminal coronary angioplasty

Characteristics of excluded studies [ordered by study ID]

Study

Reason for exclusion

Chang 2004

Patients did not undergo PCI.

Chen 2007

Intervention period was less than 3 months.

Fan 2008

Intervention period was less than 3 months.

Fu 2012

Intervention period was less than 3 months.

Gao 2007

Not RCT.

Guo 2012

Did not report outcomes listed in inclusion criteria.

Han 2009

Intervention period was less than 3 months.

Han 2011

Intervention period was less than 3 months.

Hou 2008

No full-text or data available.

Jiang 2008

Intervention was not Tong-xin-luo.

Kuang 2011

Did not report outcomes listed in inclusion criteria.

(Continued)

Li 2008

Did not report outcomes listed in inclusion criteria; randomisation not mentioned

Li 2012

Did not report outcomes listed in inclusion criteria.

Liu 2009

Intervention period was less than 3 months.

Lu 2012

Intervention period was less than 3 months.

Ma 2009

Did not report outcomes listed in inclusion criteria.

Qu 2011

Patients did not undergo PCI.

Su 2000

Patients did not undergo PCI.

Tao 2012

Did not report outcomes listed in inclusion criteria.

Tu 2006

Did not report outcomes listed in inclusion criteria.

Wang 2007

Did not report outcomes listed in inclusion criteria.

Wang 2009b

Did not report outcomes listed in inclusion criteria.

Wang 2009c

Intervention period was less than 3 months.

Wang 2012

Did not report outcomes listed in inclusion criteria.

Xiao 2004

Patients did not undergo PCI.

Xu 2007

Intervention period was less than 3 months.

Xu 2008

Not RCT, a review.

Yang 2009b

Did not report outcomes listed in inclusion criteria.

Yang 2010

Did not report outcomes listed in inclusion criteria; randomisation not mentioned

Yang 2012

Did not report outcomes listed in inclusion criteria.

Zhang 2005

Intervention period was less than 3 months.

Zhang 2006

Intervention period was less than 3 months.

Zhang 2007

Intervention period was less than 3 months.

Zhang 2008

Patients did not undergo PCI.

(Continued)

Zhang 2009b

Patients did not undergo PCI.

Zhang 2010

Didn’t report outcomes listed in inclusion criteria.

Zhao 2010

Intervention period was less than 3 months.

Zhao 2011

Intervention period was less than 3 months.

Abbreviations PCI: percutaneous coronary intervention RCT: randomised controlled trial

Characteristics of studies awaiting assessment [ordered by study ID] Deng 2013 Methods

RCT

Participants

Participants were patients diagnosed as having CHD based on the World Health Organization diagnostic criteria, who successfully received stent implantations. There were 31 patients in Tong-xin-luo group, and 30 in control group male/female: 41/20; mean age: ranging from 41 to 78.

Interventions

Tong-xin-luo

Outcomes

The minimum diameter of the target vessel, degree of stenosis; The occurrence of restenosis.

Notes

Abbreviations RCT: randomised controlled trial CHD: coronary heart disease

Characteristics of ongoing studies [ordered by study ID] Han 2012 Trial name or title

Tongxinluo Improve High on Clopidogrel Platelet Reactivityn Patients With Coronary Heart Disease

Methods

Randomised double-blind trial

Han 2012

(Continued)

Participants

ACS (including unstable angina pectoris, non-ST-segment elevation myocardial infarction and ST-elevation myocardial infarction; at least one coronary stent; age between18 and 75; high on-treatment platelet reactivity defined as an ADP-induced platelet aggregation (by VerifyNow, PRU ≥ 236) at 24 hours after clopidogrel loading (300 - 600 mg) or 24 hours after PCI

Interventions

Tong-xin-luo

Outcomes

Platelet aggregation rate; Inflammation Marker (hsCRP, CD62P-CD41); BT, FIB and aPTT; Major ischemic event (including MI, ischemic stroke and all-cause mortality); Bleeding event; Adverse drug reaction and withdrawal rate; Angina recurrence; Traditional Chinese medicine angina symptoms scores; Intra-stent thrombosis.

Starting date

November 1, 2012

Contact information

Yaling Han, MD Tel: +86-24-23922184 E-mail: [emailprotected]

Notes

Abbreviations ACS: acute coronary syndrome PRU: P2Y12 reactivity unit PCI: percutaneous coronary intervention aPTT: activated partial thromboplastin time MI: miocardial infarction

DATA AND ANALYSES

Comparison 1. Tong-xin-luo + Convetional treatment vs. Convetional treatment

Outcome or subgroup title

No. of studies

No. of participants

595

Risk Ratio (M-H, Fixed, 95% CI)

0.16 [0.07, 0.34]

1306

Risk Ratio (M-H, Fixed, 95% CI)

0.32 [0.16, 0.66]

4 11 4 5

529 1210 419 552

Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)

0.26 [0.11, 0.62] 0.24 [0.17, 0.34] 0.38 [0.06, 2.56] 0.31 [0.08, 1.12]

806

Risk Ratio (M-H, Fixed, 95% CI)

0.26 [0.15, 0.45]

1 Occurrence of angiographic restenosis 2 Occurence of myocardial infarction 3 Occurence of heart failure 4 Occurrence of angina 5 All-cause mortality 6 Mortality due to any cardiovascular event 7 Use of revascularization

Statistical method

Effect size

Analysis 1.1. Comparison 1 Tong-xin-luo + Convetional treatment vs. Convetional treatment, Outcome 1 Occurrence of angiographic restenosis. Review:

Tong-xin-luo capsule for patients with coronary heart disease after percutaneous coronary intervention

Comparison: 1 Tong-xin-luo + Convetional treatment vs. Convetional treatment Outcome: 1 Occurrence of angiographic restenosis

Study or subgroup

Tong-xin-luo

Control

n/N

Chen 2011

1/80

6/80

13.9 %

0.17 [ 0.02, 1.35 ]

Dai 2011

1/31

2/30

4.7 %

0.48 [ 0.05, 5.06 ]

Liang 2010

0/42

3/38

8.5 %

0.13 [ 0.01, 2.43 ]

Wu 2010

2/57

10/53

24.0 %

0.19 [ 0.04, 0.81 ]

Xiao 2007

2/25

6/23

14.5 %

0.31 [ 0.07, 1.37 ]

Zhou 2007b

0/70

14/66

34.5 %

0.03 [ 0.00, 0.53 ]

305

290

100.0 %

0.16 [ 0.07, 0.34 ]

Total (95% CI)

Risk Ratio

Weight

M-H,Fixed,95% CI

Risk Ratio M-H,Fixed,95% CI

Total events: 6 (Tong-xin-luo), 41 (Control) Heterogeneity: Chi2 = 2.94, df = 5 (P = 0.71); I2 =0.0% Test for overall effect: Z = 4.64 (P < 0.00001) Test for subgroup differences: Not applicable

0.01

0.1

Favours Tong-xin-luo

100

Favours control

Analysis 1.2. Comparison 1 Tong-xin-luo + Convetional treatment vs. Convetional treatment, Outcome 2 Occurence of myocardial infarction. Review:

Tong-xin-luo capsule for patients with coronary heart disease after percutaneous coronary intervention

Comparison: 1 Tong-xin-luo + Convetional treatment vs. Convetional treatment Outcome: 2 Occurence of myocardial infarction

Study or subgroup

Tong-xin-luo

Control

n/N

Di 2012

0/25

Dong 2012

1/35

1/28

3.8 %

0.80 [ 0.05, 12.23 ]

Huang 2010

2/62

5/58

17.6 %

0.37 [ 0.08, 1.85 ]

Li 2004

0/38

4/38

15.3 %

0.11 [ 0.01, 1.99 ]

Liang 2010

0/42

2/38

8.9 %

0.18 [ 0.01, 3.66 ]

Wang 2009a

1/40

4/40

13.6 %

0.25 [ 0.03, 2.14 ]

Wang 2010

1/68

2/64

7.0 %

0.47 [ 0.04, 5.06 ]

Wu 2010

0/57

2/53

8.8 %

0.19 [ 0.01, 3.79 ]

Xiao 2007

0/62

1/70

4.8 %

0.38 [ 0.02, 9.06 ]

Yang 2009a

0/30

0/29

Zhang 2009a

1/96

1/82

3.7 %

0.85 [ 0.05, 13.44 ]

Zheng 2010

1/34

3/56

7.7 %

0.55 [ 0.06, 5.07 ]

Zhou 2007b

0/70

2/66

8.8 %

0.19 [ 0.01, 3.86 ]

659

647

100.0 %

0.32 [ 0.16, 0.66 ]

Total (95% CI)

Risk Ratio

Weight

M-H,Fixed,95% CI

Risk Ratio M-H,Fixed,95% CI Not estimable

Not estimable

Total events: 7 (Tong-xin-luo), 27 (Control) Heterogeneity: Chi2 = 2.24, df = 10 (P = 0.99); I2 =0.0% Test for overall effect: Z = 3.08 (P = 0.0020) Test for subgroup differences: Not applicable

0.002

0.1

Favours Tong-xin-luo

500

Favours control

Analysis 1.3. Comparison 1 Tong-xin-luo + Convetional treatment vs. Convetional treatment, Outcome 3 Occurence of heart failure. Review:

Tong-xin-luo capsule for patients with coronary heart disease after percutaneous coronary intervention

Comparison: 1 Tong-xin-luo + Convetional treatment vs. Convetional treatment Outcome: 3 Occurence of heart failure

Study or subgroup

Tong-xin-luo

Control

n/N

Risk Ratio

Weight

Chen 2011

1/80

6/80

26.2 %

0.17 [ 0.02, 1.35 ]

Xiao 2007

1/62

7/70

28.8 %

0.16 [ 0.02, 1.27 ]

Yang 2009a

2/30

8/29

35.6 %

0.24 [ 0.06, 1.04 ]

Zhang 2009a

2/96

2/82

9.4 %

0.85 [ 0.12, 5.93 ]

Total (95% CI)

268

261

100.0 %

0.26 [ 0.11, 0.62 ]

M-H,Fixed,95% CI

Risk Ratio M-H,Fixed,95% CI

Total events: 6 (Tong-xin-luo), 23 (Control) Heterogeneity: Chi2 = 1.84, df = 3 (P = 0.61); I2 =0.0% Test for overall effect: Z = 3.01 (P = 0.0026) Test for subgroup differences: Not applicable

0.01

0.1

Favours Tong-xin-luo

100

Favours control

Analysis 1.4. Comparison 1 Tong-xin-luo + Convetional treatment vs. Convetional treatment, Outcome 4 Occurrence of angina. Review:

Tong-xin-luo capsule for patients with coronary heart disease after percutaneous coronary intervention

Comparison: 1 Tong-xin-luo + Convetional treatment vs. Convetional treatment Outcome: 4 Occurrence of angina

Study or subgroup

Tong-xin-luo

Control

n/N

Chen 2011

1/80

7/80

5.0 %

0.14 [ 0.02, 1.13 ]

Di 2012

3/25

15/25

10.7 %

0.20 [ 0.07, 0.61 ]

Li 2004

3/38

11/38

7.9 %

0.27 [ 0.08, 0.90 ]

Liang 2010

0/42

8/38

6.4 %

0.05 [ 0.00, 0.89 ]

Wang 2009a

3/40

12/40

8.6 %

0.25 [ 0.08, 0.82 ]

Wang 2010

8/68

31/64

22.9 %

0.24 [ 0.12, 0.49 ]

Wu 2010

2/57

10/53

7.4 %

0.19 [ 0.04, 0.81 ]

Xiao 2007

2/62

10/70

6.7 %

0.23 [ 0.05, 0.99 ]

Yao 2006

5/38

12/38

8.6 %

0.42 [ 0.16, 1.07 ]

Zhang 2009a

4/96

9/82

7.0 %

0.38 [ 0.12, 1.19 ]

Zhou 2007b

2/70

12/66

8.8 %

0.16 [ 0.04, 0.68 ]

616

594

100.0 %

0.24 [ 0.17, 0.34 ]

Total (95% CI)

Risk Ratio

Weight

M-H,Fixed,95% CI

Risk Ratio M-H,Fixed,95% CI

Total events: 33 (Tong-xin-luo), 137 (Control) Heterogeneity: Chi2 = 3.93, df = 10 (P = 0.95); I2 =0.0% Test for overall effect: Z = 8.01 (P < 0.00001) Test for subgroup differences: Not applicable

0.01

0.1

Favours Tong-xin-luo

100

Favours control

Analysis 1.5. Comparison 1 Tong-xin-luo + Convetional treatment vs. Convetional treatment, Outcome 5 All-cause mortality. Review:

Tong-xin-luo capsule for patients with coronary heart disease after percutaneous coronary intervention

Comparison: 1 Tong-xin-luo + Convetional treatment vs. Convetional treatment Outcome: 5 All-cause mortality

Study or subgroup

Tong-xin-luo

Control

n/N

Risk Ratio

Weight

Di 2012

0/25

Not estimable

Wang 2010

0/68

0/64

Not estimable

Yang 2009a

0/30

1/29

41.4 %

0.32 [ 0.01, 7.61 ]

Zhang 2009a

1/96

2/82

58.6 %

0.43 [ 0.04, 4.63 ]

Total (95% CI)

219

200

100.0 %

0.38 [ 0.06, 2.56 ]

M-H,Fixed,95% CI

Risk Ratio M-H,Fixed,95% CI

Total events: 1 (Tong-xin-luo), 3 (Control) Heterogeneity: Chi2 = 0.02, df = 1 (P = 0.89); I2 =0.0% Test for overall effect: Z = 0.99 (P = 0.32) Test for subgroup differences: Not applicable

0.01

0.1

Favours Tong-xin-luo

100

Favours control

Analysis 1.6. Comparison 1 Tong-xin-luo + Convetional treatment vs. Convetional treatment, Outcome 6 Mortality due to any cardiovascular event. Review:

Tong-xin-luo capsule for patients with coronary heart disease after percutaneous coronary intervention

Comparison: 1 Tong-xin-luo + Convetional treatment vs. Convetional treatment Outcome: 6 Mortality due to any cardiovascular event

Study or subgroup

Tong-xin-luo

Control

n/N

Risk Ratio

Weight

Dong 2012

1/35

2/28

23.8 %

0.40 [ 0.04, 4.19 ]

Huang 2010

0/62

2/58

27.6 %

0.19 [ 0.01, 3.82 ]

Xiao 2007

0/62

1/70

15.1 %

0.38 [ 0.02, 9.06 ]

Yang 2009a

0/30

1/29

16.3 %

0.32 [ 0.01, 7.61 ]

Zhang 2009a

0/96

1/82

17.3 %

0.29 [ 0.01, 6.91 ]

Total (95% CI)

285

267

100.0 %

0.31 [ 0.08, 1.12 ]

M-H,Fixed,95% CI

Risk Ratio M-H,Fixed,95% CI

Total events: 1 (Tong-xin-luo), 7 (Control) Heterogeneity: Chi2 = 0.17, df = 4 (P = 1.00); I2 =0.0% Test for overall effect: Z = 1.79 (P = 0.073) Test for subgroup differences: Not applicable

0.01

0.1

Favours Tong-xin-luo

100

Favours control

Analysis 1.7. Comparison 1 Tong-xin-luo + Convetional treatment vs. Convetional treatment, Outcome 7 Use of revascularization. Review:

Tong-xin-luo capsule for patients with coronary heart disease after percutaneous coronary intervention

Comparison: 1 Tong-xin-luo + Convetional treatment vs. Convetional treatment Outcome: 7 Use of revascularization

Study or subgroup

Tong-xin-luo

Control

n/N

Di 2012

7/25

9/25

15.3 %

0.78 [ 0.34, 1.76 ]

Dong 2012

0/35

6/28

12.3 %

0.06 [ 0.00, 1.05 ]

Huang 2010

2/62

4/58

7.0 %

0.47 [ 0.09, 2.46 ]

Wu 2010

2/57

10/53

17.7 %

0.19 [ 0.04, 0.81 ]

Yang 2009a

0/30

0/29

Zhang 2009a

1/96

7/82

12.9 %

0.12 [ 0.02, 0.97 ]

Zheng 2010

1/34

8/56

10.3 %

0.21 [ 0.03, 1.58 ]

Zhou 2007b

2/70

14/66

24.5 %

0.13 [ 0.03, 0.57 ]

409

397

100.0 %

0.26 [ 0.15, 0.45 ]

Total (95% CI)

Risk Ratio

Weight

M-H,Fixed,95% CI

Risk Ratio M-H,Fixed,95% CI

Not estimable

Total events: 15 (Tong-xin-luo), 58 (Control) Heterogeneity: Chi2 = 9.85, df = 6 (P = 0.13); I2 =39% Test for overall effect: Z = 4.96 (P < 0.00001) Test for subgroup differences: Not applicable

0.01

0.1

Favours Tong-xin-luo

100

Favours control

APPENDICES Appendix 1. Search strategies Cochrane Library #1 Tongxinluo #2 Tong Xin Luo #3 Tong-xin-luo #4 TXL #5 Tongxinluo* #6 Enter terms for search#1 or #2 or #3 or #4 or #5

MEDLINE 1. exp Cardiovascular Diseases/ 2. cardio*.tw. 3. cardia*.tw. 4. heart*.tw. 5. coronary*.tw. 6. angina*.tw. 7. ventric*.tw. 8. myocard*.tw. 9. pericard*.tw. 10. isch?em*.tw. 11. emboli*.tw. 12. arrhythmi*.tw. 13. thrombo*.tw. 14. atrial fibrillat*.tw. 15. tachycardi*.tw. 16. endocardi*.tw. 17. (sick adj sinus).tw. 18. exp Stroke/ 19. (stroke or stokes).tw. 20. cerebrovasc*.tw. 21. cerebral vascular.tw. 22. apoplexy.tw. 23. (brain adj2 accident*).tw. 24. ((brain* or cerebral or lacunar) adj2 infarct*).tw. 25. exp Hypertension/ 26. hypertensi*.tw. 27. peripheral arter* disease*.tw. 28. ((high or increased or elevated) adj2 blood pressure).tw. 29. exp Hyperlipidemias/ 30. hyperlipid*.tw. 31. hyperlip?emia*.tw. 32. hypercholesterol*.tw. 33. hypercholester?emia*.tw. 34. hyperlipoprotein?emia*.tw. 35. hypertriglycerid?emia*.tw. 36 or/1-35 37. tongxinluo.tw. 38. Drugs, Chinese Herbal/ 39. tong xin luo.tw. 40. (chinese adj3 (medic* or drug* or capsul*)).tw. 41. Medicine, Chinese Traditional/ 42 or/37-41 43. randomized controlled trial.pt. 44. controlled clinical trial.pt. 45. randomized.ab. 46. placebo.ab. 47. drug therapy.fs. 48. randomly.ab. 49. trial.ab. 50. groups.ab. 51. 43 or 44 or 45 or 46 or 47 or 48 or 49 or 50 Tong-xin-luo capsule for patients with coronary heart disease after percutaneous coronary intervention (Review) Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

57. exp animals/ not humans.sh. 58. 51 not 57 59 36 and 42 and 58

EMBASE #1 Tongxinluo.tw. #2 Tong xin luo.tw. #3 Tong-xin-luo.tw. #4 TXL.tw. #5 tongxinluo.mp. #6 tongxinluo$.mp. #7 #1 or #2 or #3 or #4 or #5 or #6 Wangfang (

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CONTRIBUTIONS OF AUTHORS Review design: Chen Mao and Jin-Ling Tang Protocol drafting: Chen Mao, Yafang Huang, Zu-Yao Yang and Jin-Qiu Yuan Study search and selection: Xiao-Hong Fu, Zu-Yao Yang and Jin-Qiu Yuan Data extraction: Xiao-Hong Fu and Jin-Qiu Yuan Data entering: Xiao-Hong Fu, Yafang Huang, Zu-Yao Yang, Jin-Qiu Yuan and Ying Qin Quality assessment: Vincent CH Chung, Ying Qin and Chen Mao Date analysis: Chen Mao, Wilson Wai San Tam and Jin-Ling Tang Results interpretation: Chen Mao, Xiao-Hong Fu, Yafang Huang, Jin-Qiu Yuan, Vincent CH Chung, Joey SW Kwong, Wei Xie and Jin-Ling Tang Review drafting: Chen Mao, Xiao-Hong Fu, Jin-Qiu Yuan, Yafang Huang, Zu-Yao Yang and Jin-Ling Tang Tong-xin-luo capsule for patients with coronary heart disease after percutaneous coronary intervention (Review) Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

DECLARATIONS OF INTEREST Nothing to declare.

SOURCES OF SUPPORT

Internal sources • No sources of support supplied

External sources • The Grant from the Chinese Medicine Department of Hospital Authority ( MD09948 ), Hong Kong.

DIFFERENCES BETWEEN PROTOCOL AND REVIEW In the protocol, we planned to perform subgroup analyses based on patient characteristics, type of treatment, follow-up period and type of stent. However, in this review, type of stent was not reported in most studies and it was difficult to separate participants with different baseline characteristics from original trials, so subgroup analyses based on patient characteristics or type of stent were not performed. Intervention of treatment groups in all included trials was Tong-xin-luo plus conventional treatment, so there was no obvious difference in types of treatment. Also, the follow-up period varied among studies; for most outcomes, limited studies provided outcome data according to time of follow-up, which prevented us from analysing outcome data according to the follow-up period. In addition, we planed to perform sensitivity analyses by excluding studies with high risk of bias. However, such sensitivity analyses were not performed because most of the included studies were considered to have high risk of bias. There were insufficient numbers of studies for meta-analysis after removing studies with high risk of bias. Lastly, because it is very difficult to ascribe CV death due to restenosis, we did not pool the mortality due to restenosis after PCI, which was a primary outcome in the study protocol. In addition, we did not identify any study that reported this outcome.

INDEX TERMS Medical Subject Headings (MeSH) ∗ Percutaneous

Coronary Intervention; Angina Pectoris [prevention & control]; Capsules; Cause of Death; Coronary Disease [∗ drug therapy]; Coronary Restenosis [∗ prevention & control]; Drugs, Chinese Herbal [∗ therapeutic use]; Heart Failure [prevention & control]; Myocardial Infarction [prevention & control]; Randomized Controlled Trials as Topic; Secondary Prevention [∗ methods]; Treatment Outcome

MeSH check words Humans

Tong-xin-luo capsule for patients with coronary heart disease after percutaneous coronary intervention. - PDF Download Free (2024)