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

Drug eluting and bare metal stents in people with and without diabetes: collaborative network meta-analysis

C Stettler, S Allemann, S Wandel, A Kastrati, MC Morice, A Schomig, ME Pfisterer, GW Stone, MB Leon, JS de Lezo, JJ Goy, SJ Park, M Sabate, MJ Suttorp, H Kelbaek, C Spaulding, M Menichelli, P Vermeersch, MT Dirksen, P Cervinka, M De Carlo, A Erglis, T Chechi, P Ortolani, MJ Schalij, P Diem, B Meier, S Windecker, and P Juni.

Review published: 2008.

CRD summary

This well-conducted review concluded that, in trials which specified a duration of dual antiplatelet therapy of at least 6 months after stent implantation, drug eluting stents seemed safe and effective in people both with and without diabetes. This conclusion accurately reflects an appropriate synthesis of good quality randomised controlled trials and is likely to be reliable.

Authors' objectives

To compare the effectiveness of sirolimus eluting, paclitaxel eluting and bare metal stents in people with and without diabetes mellitus.


The following databases were searched without language restriction from inception to October 2007: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials. Search terms were reported in an online appendix (Web appendix 1). In addition relevant websites, conference abstracts, reviews, book chapters, the proceedings of the Food and Drug Administration and references were checked. Manufacturers and trialists were also contacted.

Study selection

Randomised controlled trials (RCTs) which compared at least two of the Taxus paclitaxel eluting stent, the Cypher sirolimus eluting stent and bare metal stents in people with symptoms or signs of myocardial ischemia as a result of coronary artery disease were eligible for inclusion in the review. Trials had to have a follow-up of at least 6 months. The primary outcomes were overall mortality and target lesion revascularisation. The secondary outcomes were: cardiac death, procedure related death, death related to concomitant treatment and death from unknown cause; myocardial infarction; composite of death or myocardial infarction; and stent thrombosis within the stented segment. Detailed definitions were provided for outcomes.

All included trials employed dual antiplatelet therapy for durations ranging from 2 to 12 months. Limited information on study characteristics was provided for some included studies. Approximately one third of trial participants had diabetes mellitus. All three types of stents were well-represented in the included trials.

The authors did not state how the papers were selected for the review, or how many reviewers performed the selection.

Assessment of study quality

Two reviewers independently assessed the studies for validity using the following criteria: allocation concealment, blinding of outcome assessors, and use of an intention-to-treat (ITT) analysis. Disagreements were resolved through consultation with a third reviewer.

Data extraction

Two reviewers independently extracted the data and disagreements were resolved through consultation with a third reviewer. Data on numbers of events for each outcome were recorded separately for years 1 to 4. Authors and manufacturers were asked to check data and provide additional information using a standardised form. Attempts were made to obtain outcome data separately for those with and without diabetes. Durations of dual antiplatelet therapy were estimated using related variables and classified in increments of 10% where this information was not reported. Trial dates were estimated from the month of completion of patient recruitment. Stent thrombosis was recorded using the per protocol definitions of primary studies as well as using definitions designed to include the incidence of secondary thrombosis.

Methods of synthesis

A Bayesian hierarchical random-effects model for mixed treatment comparisons based on piece-wise constant hazards was employed to calculate hazard ratios (HRs) with 95% credibility intervals (Ci). The model included random effects at the level of trials, adjacent time periods and comparisons. Time periods with zero events in both groups were excluded from the analyses. For the outcome of stent thrombosis relative risks were derived using a Poisson regression model. Inconsistency was assessed by the calculation of inconsistency factors and back transformations were used to express inconsistency as a percentage difference in HRs between direct within-trial and indirect between-trial comparisons. The goodness of fit of the model to the data was also evaluated. Trial characteristics such as length of follow-up (at least two years versus less than 2 years), recent completion of patient recruitment (before/after January 2004) and duration of antiplatelet therapy (6 months versus less than 6 months) were included as covariates in the network meta-analysis and interactions were assessed for statistical significance.

Results of the review

Thirty-five RCTs (n = 14,799) were included in the review. 29 RCTs had adequate allocation concealment, 28 trials employed blinded outcome assessment, 30 trials used an ITT analysis, and 24 trials met all three criteria. Eight trials had duration of antiplatelet therapy of less than 6 months and compared sirolimus eluting with bare metal stents.

People with diabetes: The pooled HR for mortality was 1.14 (95% Ci: 0.74, 1.60) for sirolimus eluting versus bare metal stents;1.09 (95% Ci: 0.71, 1.66) for paclitaxel eluting versus bare metal stents; and 1.02 (95% Ci: 0.70, 1.57) for sirolimus versus paclitaxel eluting stents. A moderate to high level of inconsistency was detected (61%).

People without diabetes: The pooled HR for mortality was 1.02 (95% Ci: 0.77, 1.29) for sirolimus eluting versus bare metal stents; 0.90 (95% Ci: 0.67, 1.16) for paclitaxel eluting versus bare metal stents; and 1.13 (95% Ci: 0.83, 1.54) for sirolimus versus paclitaxel eluting stents. There was no evidence of inconsistency.

There was a strong statistically significant decrease in revascularisation of target lesions associated with both drug eluting stents (sirolimus eluting versus bare metal stent HR 0.29, 95% Ci: 0.22, 0.29; paclitaxel eluting versus bare metal stent HR 0.38, 95% Ci: 0.28, 0.55) but no significant difference between the two drug-eluting stents.

A restricted network analysis of trials with dual antiplatelet therapy for at least 6 months produced similar results with lower inconsistency and narrower credibility intervals. While the incidence of death was about twice as high in patients with diabetes as in those without, there was no statistically significant interaction between treatment effect and diabetes status. Results for secondary safety outcomes were also reported for both the main and restricted network meta-analyses.

Authors' conclusions

In trials which specified a duration of dual antiplatelet therapy of at least 6 months after stent implantation, drug eluting stents seemed safe and effective in people both with and without diabetes.

CRD commentary

The review question and inclusion criteria were clear and specific. The authors searched a number of relevant databases and other sources without language restrictions, thereby reducing the potential for language or publication bias and the chances that relevant studies were excluded. The authors reported using rigorous methodology for the extraction of data and the assessment of validity but not for the selection of studies. An appropriate validity assessment was undertaken and was used to inform the synthesis. The synthesis appeared appropriate and included provision for thorough investigation of potential sources of heterogeneity. The authors' conclusions reflected the results of the review and are likely to be reliable.

Implications of the review for practice and research

Practice: The authors stated that it is prudent to adhere to a minimum duration of dual antiplatelet therapy of 6 months in patients undergoing implantation of a drug eluting coronary stent.

Research: The authors stated that an expansion of the current network meta-analysis will be required in due course to incorporate the results of trials of novel second generation drug eluting stents. They also stated that adequately powered RCTs will be required to determine the optimum duration of dual antiplatelet therapy.


Swiss National Science Foundation, grant numbers 3233B0-115212, 3233-066377, 3200-066378; Swiss National Science Foundation, National Research Programme 53, grant number 405340-104762; A large number of financial relationships with pharmaceutical companies were declared.

Bibliographic details

Stettler C, Allemann S, Wandel S, Kastrati A, Morice M C, Schomig A, Pfisterer M E, Stone G W, Leon M B, de Lezo J S, Goy J J, Park S J, Sabate M, Suttorp M J, Kelbaek H, Spaulding C, Menichelli M, Vermeersch P, Dirksen M T, Cervinka P, De Carlo M, Erglis A, Chechi T, Ortolani P, Schalij M J, Diem P, Meier B, Windecker S, Juni P. Drug eluting and bare metal stents in people with and without diabetes: collaborative network meta-analysis. BMJ 2008; 337:a1331. [PMC free article: PMC2527175] [PubMed: 18757996]

Other publications of related interest

Stettler C, Wandel S, Allemann S, et al. Outcomes associated with drug-eluting and bare-metal stents: a collaborative network meta-analysis. Lancet 2007;370:937-48.

Indexing Status

Subject indexing assigned by NLM


Blood Vessel Prosthesis; Coronary Restenosis /prevention & control; Diabetic Angiopathies /drug therapy; Drug-Eluting Stents; Humans; Paclitaxel /administration & dosage; Platelet Aggregation Inhibitors /administration & dosage; Prosthesis Failure; Randomized Controlled Trials as Topic; Sirolimus /administration & dosage; Stents



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: 18757996