ArticlesStent thrombosis with drug-eluting and bare-metal stents: evidence from a comprehensive network meta-analysis
Introduction
Randomised controlled trials,1, 2 meta-analysis,3 and observational studies4 have consistently shown reduced rates of angiographic restenosis and ischaemia-driven target vessel revascularisation with drug-eluting stents compared with bare-metal stents. As a result, most percutaneous coronary interventions in Europe and the USA are done with drug-eluting rather than bare-metal stents. However, the high rates of early and late stent thrombosis after discontinuation of dual antiplatelet agents with drug-eluting stents, and the ongoing propensity for thrombosis after the first year with first-generation Cypher sirolimus-eluting stents (SES; Cordis Corp, Miami Lakes, FL, USA) and Taxus paclitaxel-eluting stents (PES; Boston Scientific, Natick, MA, USA), have raised safety concerns.5, 6 To address these issues, new drug-eluting stents have been developed with novel materials, designs, and delivery systems, with improved biocompatible polymers, and new antiproliferative agents compared with their predecessors. However, most of these second generation stents were approved in non-inferiority trials compared with first generation drug-eluting stents.7, 8, 9, 10 Therefore, few studies have directly compared second generation drug-eluting stents with each other11 or with bare-metal stents. Recently, the EXAMINATION trial12 comparing Xience V cobalt-chromium everolimus-eluting stents (CoCr-EES; Abbott Vascular, Santa Clara, CA, USA) with bare-metal stents in patients with ST-segment elevation myocardial infarction (STEMI) showed significantly reduced rates of stent thrombosis in patients treated with CoCr-EES. However, this trial was not powered to show differences in stent thrombosis and therefore whether those findings are real or attributable to chance remains unclear.
In view of the low frequency of stent thrombosis, very large sample sizes are needed to accurately estimate treatment differences between devices. Network meta-analysis and mixed treated comparisons are novel research methods capable of comparing different treatments using a common reference treatment, and their role in clinical research has been established.13 An earlier network meta-analysis in 2007 in which only bare-metal stents and first generation drug-eluting stents were compared strengthened concerns about late and very late stent thrombosis with PES.14 Since that publication, many additional randomised trials have been done with second generation as well as first generation drug-eluting stents. Accordingly, we undertook an updated contemporary, comprehensive network meta-analysis to investigate whether there are major differences in the risk of stent thrombosis between first and second generation drug-eluting stents, or between drug-eluting and bare-metal stents.
Section snippets
Study design
In this network meta-analysis, we compared the risk of definite and definite or probable stent thrombosis between drug-eluting stents currently approved by the US Food and Drug Administration (FDA) and between drug-eluting and bare-metal stents. We restricted our analyses to FDA-approved drug-eluting stents because these currently are the devices with the most robust demonstrations of safety and efficacy. Thus, the drug-eluting stents studied in the present report were SES, PES (both Express
Results
Figure 1 shows the flow diagram for the study analysis. Of 2602 potentially relevant articles initially screened, 49 trials met the inclusion criteria and were included in the final meta-analysis (appendix pp 1–5), with a total of 50 844 patients. Figure 2 shows the evidence network. Table 1 shows the major characteristics of the included trials. Six studies were done exclusively in patients with diabetes, 11 studies in patients with STEMI, one study in patients with saphenous vein grafts, one
Discussion
We report the largest and most comprehensive study to date comparing the rates of ARC definite and definite or probable stent thrombosis between different types of drug-eluting stent and between drug-eluting and bare-metal stents. There were three principal findings: (1) CoCr-EES were associated with significantly lower rates of 1-year and 2-year definite stent thrombosis than were bare-metal stents, a result not present with other drug-eluting stents; (2) the reduction in stent thrombosis with
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