Elsevier

The Lancet

Volume 370, Issue 9591, 15–21 September 2007, Pages 937-948
The Lancet

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Outcomes associated with drug-eluting and bare-metal stents: a collaborative network meta-analysis

https://doi.org/10.1016/S0140-6736(07)61444-5Get rights and content

Summary

Background

Whether the two drug-eluting stents approved by the US Food and Drug Administration—a sirolimus-eluting stent and a paclitaxel-eluting stent—are associated with increased risks of death, myocardial infarction, or stent thrombosis compared with bare-metal stents is uncertain. Our aim was to compare the safety and effectiveness of these stents.

Methods

We searched relevant sources from inception to March, 2007, and contacted investigators and manufacturers to identify randomised controlled trials in patients with coronary artery disease that compared drug-eluting with bare-metal stents, or that compared sirolimus-eluting stents head-to-head with paclitaxel-eluting stents. Safety outcomes included mortality, myocardial infarction, and definite stent thrombosis; the effectiveness outcome was target lesion revascularisation. We included 38 trials (18 023 patients) with a follow-up of up to 4 years. Trialists and manufacturers provided additional data on clinical outcomes for 29 trials. We did a network meta-analysis with a mixed-treatment comparison method to combine direct within-trial comparisons between stents with indirect evidence from other trials while maintaining randomisation.

Findings

Mortality was similar in the three groups: hazard ratios (HR) were 1·00 (95% credibility interval 0·82–1·25) for sirolimus-eluting versus bare-metal stents, 1·03 (0·84–1·22) for paclitaxel-eluting versus bare-metal stents, and 0·96 (0·83–1·24) for sirolimus-eluting versus paclitaxel-eluting stents. Sirolimus-eluting stents were associated with the lowest risk of myocardial infarction (HR 0·81, 95% credibility interval 0·66–0·97, p=0·030 vs bare-metal stents; 0·83, 0·71–1·00, p=0·045 vs paclitaxel-eluting stents). There were no significant differences in the risk of definite stent thrombosis (0 days to 4 years). However, the risk of late definite stent thrombosis (>30 days) was increased with paclitaxel-eluting stents (HR 2·11, 95% credibility interval 1·19–4·23, p=0·017 vs bare-metal stents; 1·85, 1·02–3·85, p=0·041 vs sirolimus-eluting stents). The reduction in target lesion revascularisation seen with drug-eluting stents compared with bare-metal stents was more pronounced with sirolimus-eluting stents than with paclitaxel-eluting stents (0·70, 0·56–0·84; p=0·0021).

Interpretation

The risks of mortality associated with drug-eluting and bare-metal stents are similar. Sirolimus-eluting stents seem to be clinically better than bare-metal and paclitaxel-eluting stents.

Introduction

The long-term safety of the two polymer-based drug-eluting stents approved by the US Food and Drug Administration (FDA)—a sirolimus-eluting stent and a paclitaxel-eluting stent—was questioned by recent studies, which reported increased rates of death, myocardial infarction, or late stent thrombosis compared with bare-metal stents.1, 2, 3, 4, 5 These studies were hampered by few patients, limited durations of follow-up, or an observational study design.

Network meta-analyses6, 7 or mixed treatment comparisons8, 9, 10 would allow us to do a unified, coherent analysis of all randomised controlled trials that compared either of the two drug-eluting stents with bare-metal stents or the two drug-eluting stents head-to-head, while fully respecting randomisation. We established a collaborative group of investigators who provided trial data based on standardised definitions of outcomes,11, 12 and did a network meta-analysis.

Section snippets

Search strategy and selection criteria

We searched Medline, EmBase, the Cochrane Central Register of Controlled Trials (CENTRAL), and relevant websites (www.acc.org, www.tctmd.com, www.theheart.org, www.clinicaltrialresults.org) for studies in any language (from the inception of each database to March, 2007), searched reference lists and conference abstracts by hand, checked relevant reviews, book chapters, and the proceedings of the relevant FDA advisory panels, and contacted manufacturers and trialists. Two investigators (CSt, SA)

Results

We screened the titles and abstracts of 870 potentially eligible reports, examined the full text of 84 articles reporting on 41 different trials, and identified 38 trials13, 14, 15, 20, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58 that met our inclusion criteria (figure 1). Investigators or manufacturers provided data for 29 trials.13, 14, 20, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 36, 37, 38, 39, 40, 43,

Discussion

Our collaborative network meta-analysis indicates that drug-eluting stents and bare-metal stents are associated with similar rates of overall and cardiac mortality, and that use of sirolimus-eluting stents is associated with a reduction in the risk of myocardial infarction compared with use of bare-metal and paclitaxel-eluting stents. About 100 patients will have to receive sirolimus-eluting stents, rather than bare-metal or paclitaxel-eluting stents, to prevent one myocardial infarction over 4

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