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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].

A meta-analysis of randomized controlled trials appraising the efficacy and safety of cilostazol after coronary artery stent implantation

JS Jang, HY Jin, JS Seo, TH Yang, DK Kim, DS Kim, DK Kim, SH Seol, DI Kim, KI Cho, BH Kim, YH Park, HG Je, YH Jeong, WJ Kim, JY Lee, and SW Lee.

Review published: 2012.

Link to full article: [Journal publisher]

CRD summary

This review concluded that cilostazol added to aspirin and thienopyridine seemed effective in reducing the risk of restenosis and repeat revascularisation after percutaneous coronary interventions. Most of the studies were subject to a high risk of bias. Despite this the review was well-conducted and results of the included studies were consistent; the overall conclusion is likely to be reliable.

Authors' objectives

To evaluate the impact of cilostazol on angiographic and clinical outcomes in patients who underwent percutaneous coronary intervention (PCI) with stents and treated with aspirin and thienopyridine.


MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched without language restrictions from 2001 to March 2012; search terms were reported. Reference lists of included studies and meta-analyses were searched.

Study selection

Randomised controlled trials (RCTs) that compared antiplatelet therapy using aspirin and a thienopyridine with and without cilostazol in patients who underwent stent implantation were eligible for inclusion. Studies had to report angiographic or clinical outcomes beyond platelet function; the primary outcomes were in-segment late loss and angiographic restenosis.

Across the trial arms, mean ages ranged from 57 to 68 years, 58% to 76% of participants were male, 46% to 69% had hypertension, 20% to 100% had diabetes, where reported 34% to 100% had acute coronary syndrome and mean left ventricular ejection fraction ranged from 55% to 62%. Most studies used various drug-eluting stents. Most of the included studies were conducted in high-risk populations. Most studies were conducted in Asian countries.

Two independent reviewers selected studies for the review; disagreements were resolved by consensus.

Assessment of study quality

Two independent reviewers assessed study quality in terms of randomisation, allocation concealment, completeness data and blinding of outcome assessors.

Data extraction

Two independent reviewers extracted data to calculate odds ratios (OR) for binary outcomes and mean differences for continuous outcomes, with 95% confidence intervals (CI).

Methods of synthesis

Pooled odds ratios and weighted mean differences (WMD), with 95% CI, were calculated using a fixed-effect model where heterogeneity was absent and random-effects where heterogeneity was present. Heterogeneity was investigated using the Cochran Q and Ι² statistics. Subgroup analyses were used to investigate the impact of stent type. Sensitivity analyses were conducted to assess the impact of individual trials. Potential for publication bias was assessed using the Duval and Tweedie trim and fill method and Egger's regression.

Results of the review

Eleven RCTs were included in the review. Follow-up ranged from one to 12 months. Four studies had a low risk of selection bias, three had a low risk of performance bias, three had a low risk of attrition bias, two had a low risk of detection bias and four were considered to have adequately adjusted for potential confounders.

Adding cilostazol to dual therapy with aspirin and a thienopyridine reduced in-segment late loss (WMD 0.14, 95% CI 0.08 to 0.20; Ι²=54%), angiographic restenosis (OR 0.58, 95% CI 0.48 to 0.71; Ι²=0%), target lesion revascularisation (OR 0.56, 95% CI 0.41 to 0.77; seven studies; Ι²=16%) and major adverse cardiovascular events (OR 0.72, 95% CI 0.60 to 0.86; 10 studies; Ι²=14%). There was no impact on mortality (seven studies), stent thrombosis (seven studies) and major bleeding (seven studies).

There was no strong evidence for publication bias. Results for bare-metal and drug-eluting stents individually were reported.

Authors' conclusions

Cilostazol in addition to dual antiplatelet therapy appeared to be effective in reducing the risk of restenosis and repeat revascularisation after PCI without any significant benefits for mortality or stent thrombosis.

CRD commentary

The review addressed a clear review question supported by reproducible inclusion criteria. Relevant sources were searched without language restrictions. There seemed to be no specific attempt to locate unpublished studies. Each stage of the review process was conducted in duplicate, which reduced the risk of error and bias. Appropriate criteria were used to assess study quality and the results were reported in full. Most of the studies had a period of follow-up of six months or less, which the authors acknowledged as a limitation of the evidence. Appropriate methods of synthesis were used.

This was generally a well-conducted review but most of the included studies were subject to a high risk of bias and the reliability of the results of the primary studies, and therefore the pooled results, was uncertain. Despite this, the results of the included studies were consistent for most outcomes and the overall conclusion is likely to be reliable.

Implications of the review for practice and research

Practice: The authors stated that the benefit of triple therapy could be more pronounced in patients with long coronary lesions and in diabetic patients who were at higher risk of restenosis. They went on to state that the lack of any study demonstrating the superiority of dual antiplatelet therapy suggested that cilostazol-based triple therapy should be the optimal antiplatelet regimen in high-risk patients undergoing stent-based PCI.

Research: The authors did not report implications for research.


Korea Science and Engineering Foundation; Ministry of Education, Science and Engineering, Korea.

Bibliographic details

Jang JS, Jin HY, Seo JS, Yang TH, Kim DK, Kim DS, Kim DK, Seol SH, Kim DI, Cho KI, Kim BH, Park YH, Je HG, Jeong YH, Kim WJ, Lee JY, Lee SW. A meta-analysis of randomized controlled trials appraising the efficacy and safety of cilostazol after coronary artery stent implantation. Cardiology 2012; 122(3): 133-143. [PubMed: 22832424]

Indexing Status

Subject indexing assigned by NLM


Aspirin /therapeutic use; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation /methods; Combined Modality Therapy; Coronary Restenosis /prevention & control; Drug Therapy, Combination; Female; Graft Occlusion, Vascular /prevention & control; Humans; Male; Middle Aged; Percutaneous Coronary Intervention /methods; Platelet Aggregation Inhibitors /therapeutic use; Pyridines /therapeutic use; Randomized Controlled Trials as Topic; Stents; Tetrazoles /therapeutic use; Ticlopidine /analogs & derivatives /therapeutic use; Treatment Outcome



Database entry date


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: 22832424

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