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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Cilostazol-based triple antiplatelet therapy compared to dual antiplatelet therapy in patients with coronary stent implantation: a meta-analysis of 5,821 patients

DF Geng, M Liu, DM Jin, W Wu, J Deng, and JF Wang.

Review published: 2012.

Link to full article: [Journal publisher]

CRD summary

This review concluded that adding cilostazol to dual antiplatelet therapy was effective and relatively safe in preventing major adverse cardiovascular events after coronary stenting, particularly in people at high risk of restenosis or clinical events. Limited reporting about participants and treatment regimes made generalisability of results unclear and some studies were low quality. The conclusions should be treated with caution.

Authors' objectives

To assess the effects of cilostazol-based triple antiplatelet therapy compared to dual antiplatelet therapy in people who received coronary artery stents.

Searching

PubMed, EMBASE, BIOSIS previews, Cochrane Central Register of Controlled Trials (CENTRAL) and CNKI were searched to September 2011. Search terms were reported. Reference list of identified studies, three relevant conference proceedings and three websites/trials registries were checked. No language or publication restrictions were applied.

Study selection

Randomised controlled trials (RCTs) that lasted at least six months in people who underwent coronary artery stenting and that compared triple antiplatelet therapy (cilostazol, aspirin and clopidogrel) to dual antiplatelet therapy (aspirin and clopidogrel) were eligible for inclusion. The primary outcome of interest was major cardiovascular events (composite of death, myocardial infarction, stroke and target lesion/vessel revascularisation). Secondary outcomes were death, myocardial infarction, stroke, target lesion/vessel revascularisation, cardiovascular thrombotic events (composite of cardiac death, non-fatal myocardial infarction and stroke), stent thrombosis, bleeding events, net adverse clinical events (composite of major bleeding and major cardiovascular events) and angiographic findings at follow-up (binary restenosis ≥50% at angiography, diameter stenosis and late lumen loss).

Most of the included studies were undertaken in Chinese or Korean populations. Cilostazol 200mg was given in addition to aspirin and clopidogrel. In one study ticlopidine was used instead of clopidogrel for some participants. Some studies used bare metal stents, some used drug eluting stents and some used both.

The authors did not state how many reviewers selected studies for inclusion.

Assessment of study quality

Quality was assessed using Cochrane Collaboration methods based on risk of bias in selection, performance, detection and attrition.

The authors did not state how many reviewers assessed quality.

Data extraction

Data were extracted to calculate odds ratios (ORs) and 95% confidence intervals (CI) for dichotomous data and mean differences and 95% confidence intervals for continuous data.

Data were extracted independently by two reviewers. Disagreements were resolved by consensus or a third reviewer.

Methods of synthesis

Pooled odds ratios and 95% confidence intervals and weighted mean differences (WMDs) and 95% confidence intervals were calculated using a random-effects model. Heterogeneity was assessed using Χ² and Ι². Subgroup analyses investigated different stents (bare metal, drug eluting) and participant characteristics (diabetes, acute coronary syndrome, long lesions, small vessels, high platelet aggregability).

Results of the review

Fourteen RCTs (5,821 participants, range 59 to 1,212) were included. Follow-up in one trial was 24 months and in others ranged from six to 12 months.

Six RCTs were considered to be at low risk of bias and seven were considered to be at high risk of bias; quality was not reported for one trial.

Compared to dual antiplatelet therapy, triple antiplatelet therapy reduced major cardiovascular events (OR 0.59, 95% CI 0.46 to 0.76; Ι²=44%; 14 trials), the rate of target vessel revascularisation (OR 0.65, 95% CI 0.51 to 0.83; nine trials), target lesion revascularisation (OR 0.50, 95% CI 0.32 to 0.79; five trials), net adverse events (OR 0.69, 95% CI 0.55 to 0.86; 10 trials), binary stenosis (OR 0.53, 95% CI 0.42 to 0.67; eight trials) and a decrease in late lumen loss (WMD -0.17mm, 95% CI -0.21 to -0.12; seven trials) and diameter stenosis (WMD -5.41%, 95% CI -8.94 to -1.87; six trials). There was a reduction in cardiovascular thrombotic events that just failed to reach statistical significance (OR 0.61, 95% CI 0.37 to 1.00; six trials).

There were no statistically significant differences for all-cause death (14 trials), cardiac death (10 trials), myocardial infarction (12 trials), stent thrombosis (nine trials), major bleeding (10 trials) and total bleeding (13 trials).

Drug discontinuation occurred more frequently in the triple therapy groups (OR 3.62, 95% CI 1.88 to 6.95). Common side-effects included skin rash, headache, gastrointestinal disturbances and palpitations.

In subgroup analyses, results for major adverse cardiovascular events were similar to the main analysis for different subgroups of participants and with drug eluting stents but not with bare metal stents (where there was no statistically significant difference). Other subgroup analyses were reported.

Authors' conclusions

The addition of cilostazol to standard dual antiplatelet therapy was effective and relatively safe in preventing major adverse cardiovascular events after coronary stenting, particularly in people at high risk of restenosis or clinical events.

CRD commentary

The aims of this review were clearly stated in terms of the inclusion criteria. The search was unrestricted by language and publication status which likely reduced any possible language or publication bias. Methods of data extraction were aimed at reducing possible reviewer error and bias; methods for study selection and quality assessment were unclear. Study quality was assessed using an appropriate method but reporting of the assessment was limited.

Methods of synthesis appeared generally appropriate but full details were not presented for most analyses and although heterogeneity was assessed it was not generally reported so it was difficult to reliably comment on the methods used. The details of the included studies were not presented clearly. In particular, there was no information about one study and the characteristics of participants, duration of drug use and any concomitant therapies were not reported and this made it difficult to comment on the generalisability of the results. There were some discrepancies between numbers in the text and tables.

Some aspects of reporting were limited and more than half of the included studies were considered of low methodological quality so the review conclusions should be treated with some caution.

Implications of the review for practice and research

Practice: The authors stated that caution should be used when generalising the results in all lesion subsets.

Research: The authors stated a need for further research to assess the effects of triple antiplatelet therapy in people from ethnic groups other than Chinese and Korean who underwent stent implantation and whether it had a beneficial effect on stent thrombosis in people at high risk of thrombosis.

Funding

Not stated.

Bibliographic details

Geng DF, Liu M, Jin DM, Wu W, Deng J, Wang JF. Cilostazol-based triple antiplatelet therapy compared to dual antiplatelet therapy in patients with coronary stent implantation: a meta-analysis of 5,821 patients. Cardiology 2012; 122(3): 148-157. [PubMed: 22832561]

Indexing Status

Subject indexing assigned by NLM

MeSH

Acute Coronary Syndrome /drug therapy; Aspirin /therapeutic use; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation /methods; Coronary Restenosis /prevention & control; Drug Therapy, Combination; Hemorrhage /chemically induced; Humans; Myocardial Infarction /prevention & control; Platelet Aggregation Inhibitors /therapeutic use; Randomized Controlled Trials as Topic; Stents; Stroke /prevention & control; Tetrazoles /therapeutic use; Ticlopidine /analogs & derivatives /therapeutic use; Treatment Outcome

AccessionNumber

12012041474

Database entry date

18/12/2012

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 22832561

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