Elsevier

The Lancet

Volume 364, Issue 9434, 14–20 August 2004, Pages 583-591
The Lancet

Articles
A hierarchical Bayesian meta-analysis of randomised clinical trials of drug-eluting stents

https://doi.org/10.1016/S0140-6736(04)16850-5Get rights and content

Summary

Background

Drug-eluting stents (DES) are associated with lower restenosis rates than bare-metal stents (BMS), but the benefits and safety of the new devices have not been systematically quantified across different trials. We undertook a meta-analysis of randomised trials comparing BMS and stents eluting sirolimus or paclitaxel.

Methods

A systematic literature search aimed to identify all randomised clinical trials with 6–12 months of clinical follow-up. Results were pooled by a hierarchical Bayesian random-effects model with prespecified stratification for drug and the presence of carrier polymer. The primary outcomes examined were rates of death, myocardial infarction, target-lesion revascularisation, major adverse cardiac events (death, myocardial infarction, and target-vessel revascularisation), and angiographic restenosis.

Findings

We identified 11 eligible trials involving 5103 patients. The pooled mortality rates were low for both DES and BMS with no evidence of any difference between them (odds ratio 1·11 [95% credible interval 0·61–2·06]). Pooled rates of myocardial infarction showed no between-group difference (0·92 [0·65–1·25]). The rate of major adverse cardiac events was 7·8% with DES and 16·4% with BMS (0·42 [0·32–0·53]), and the angiographic restenosis rates were also lower for DES (8·9% vs 29·3%; 0·18 [0·06–0·40]). The pooled rates of major adverse cardiac events for each DES type and the respective BMS were: for sirolimus, 6·8% versus 21·0% (0·28 [0·17–0·41]); for polymer-based paclitaxel 8·7% versus 16·7% (0·47 [0·25–0·71]); and for non-polymer-based paclitaxel 7·7% versus 9·5% (0·64 [0·42–1·00]). We did not observe higher rates of edge restenosis, stent thrombosis, or late incomplete stent apposition with DES, although the credible intervals were wide.

Interpretation

Sirolimus-eluting and polymeric paclitaxel-eluting stents are effective at decreasing rates of angiographic restenosis and major adverse cardiac events compared with BMS. However, there is no evidence that they affect mortality or myocardial-infarction rates. They also appear to be safe in the short to medium term, although definitive conclusions are not possible. Larger studies with longer follow-up are needed to define better the role of these new devices.

Introduction

During the past decade, the use of stents has become common practice during percutaneous coronary intervention both to treat acute complications of balloon angioplasty and to decrease rates of angiographic restenosis.1, 2 However, rates of angiographic restenosis even in patients who receive stents are 15–40% at 6 months.3 Restenosis after percutaneous coronary intervention with stenting occurs primarily within the stent (in-stent restenosis) and is almost entirely due to neointimal hyperplasia.4, 5 Studies evaluating stents coated with antimitotic drugs have shown promise at reducing restenosis rates.6 These drugs are commonly released in a controlled way from biocompatible polymer coatings that act as drug reservoirs.7 Medium-term results from several randomised clinical trials suggest that drug-eluting stents (DES) substantially lower rates of angiographic restenosis and the subsequent need for repeat revascularisation procedures compared with bare-metal stents (BMS). However, there have been concerns about the safety of DES, because rare but clinically important complications may become apparent only in larger or combined studies.8, 9 We therefore undertook a meta-analysis of all randomised clinical trials examining DES to quantify more accurately their effect on clinical events and restenosis rates.

Section snippets

Search strategy

We carried out this meta-analysis in accordance with the standard protocol recommended by the Quality of Reporting of Meta-analyses group.10 We searched the PubMed database (Dec 16, 1998, to April 18, 2004) with the keywords “drug*” and “restenosis”. 1137 papers were discovered. The titles were screened so that antimitotic drugs currently under investigation for the treatment of restenosis could be identified. We defined antimitotic drugs as agents that directly inhibit the cell cycle. We then

Results

Our literature search identified 15 randomised clinical trials (figure 1), involving 5835 patients, that investigated DES, including four with sirolimus, seven with paclitaxel, and four with other drugs (table 1).15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 Two trials examining stents eluting QP2 and dactinomycin were terminated prematurely owing to adverse events and had incomplete follow-up reporting.27, 28 In view of the heterogeneity of the antimitotic drugs and polymer

Discussion

The objective of our meta-analysis was to quantify the treatment effect and safety of DES. We found no evidence that DES have any effect on medium-term mortality or rates of myocardial infarction, although further data are needed before definitive conclusions can be drawn. However, the restenosis rate on routine follow-up angiography was substantially lower with DES than with BMS, with consequent reductions in rates of target-lesion revascularisation and major adverse cardiac events. These

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