Comparison of Zotarolimus-Eluting and Everolimus-Eluting Coronary Stents

Published at www.nejm.org June 16, 2010 (10.1056/NEJMoa1004130)

Comparison of Zotarolimus-Eluting and Everolimus-Eluting Coronary Stents

Patrick W. Serruys, M.D., Ph.D., Sigmund Silber, M.D., Ph.D., Scot Garg, M.B., Ch.B., M.R.C.P., Robert Jan van Geuns, M.D., Ph.D., Gert Richardt, M.D., Pawel E. Buszman, M.D., Ph.D., Henning Kelbæk, M.D., Adrianus Johannes van Boven, M.D., Ph.D., Sjoerd H. Hofma, M.D., Ph.D., Axel Linke, M.D., Ph.D., Volker Klauss, M.D., Ph.D., William Wijns, M.D., Ph.D., Carlos Macaya, M.D., Ph.D., Philippe Garot, M.D., Carlo DiMario, M.D., Ph.D., Ganesh Manoharan, M.B., B.Ch., M.D., F.R.C.P., Ran Kornowski, M.D., Thomas Ischinger, M.D., Ph.D., Antonio Bartorelli, M.D., Jacintha Ronden, Ph.D., Marco Bressers, M.Sc., Pierre Gobbens, B.Sc., Manuela Negoita, M.D., Frank van Leeuwen, M.D., and Stephan Windecker, M.D.


ABSTRACT

Background New-generation coronary stents that release zotarolimus or everolimus have been shown to reduce the risk of restenosis. However, it is unclear whether there are differences in efficacy and safety between the two types of stents on the basis of prospectively adjudicated end points endorsed by the Food and Drug Administration.

Methods In this multicenter, noninferiority trial with minimal exclusion criteria, we randomly assigned 2292 patients to undergo treatment with coronary stents releasing either zotarolimus or everolimus. Twenty percent of patients were randomly selected for repeat angiography at 13 months. The primary end point was target-lesion failure, defined as a composite of death from cardiac causes, any myocardial infarction (not clearly attributable to a nontarget vessel), or clinically indicated target-lesion revascularization within 12 months. The secondary angiographic end point was the extent of in-stent stenosis at 13 months.

Results At least one off-label criterion for stent placement was present in 66% of patients. The zotarolimus-eluting stent was noninferior to the everolimus-eluting stent with respect to the primary end point, which occurred in 8.2% and 8.3% of patients, respectively (P<0.001 for noninferiority). There were no significant between-group differences in the rate of death from cardiac causes, any myocardial infarction, or revascularization. The rate of stent thrombosis was 2.3% in the zotarolimus-stent group and 1.5% in the everolimus-stent group (P=0.17). The zotarolimus-eluting stent was also noninferior regarding the degree (±SD) of in-stent stenosis (21.65±14.42% for zotarolimus vs. 19.76±14.64% for everolimus, P=0.04 for noninferiority). In-stent late lumen loss was 0.27±0.43 mm in the zotarolimus-stent group versus 0.19±0.40 mm in the everolimus-stent group (P=0.08). There were no significant between-group differences in the rate of adverse events.

Conclusions At 13 months, the new-generation zotarolimus-eluting stent was found to be noninferior to the everolimus-eluting stent in a population of patients who had minimal exclusion criteria. (ClinicalTrials.gov number, NCT00617084 [ClinicalTrials.gov] .)


The use of early drug-eluting stents consisting of a metal platform and the controlled release of a therapeutic agent from a durable polymer matrix has partially addressed the problem of restenosis.1,2 Although these first-generation polymers were considered biocompatible, they have been associated with allergic reactions and inflammation, which in combination with incomplete strut endothelialization have led to early and late stent thrombosis.3
New-generation polymer coatings aim more specifically at mimicking the endothelial lining in order to prevent thrombotic complications. In addition, basic research has shown that some of these polymeric materials could potentially up-regulate genes related to thrombosis, inflammation, and vasoconstriction.4 The polymer used with the Resolute zotarolimus-eluting stent (Medtronic CardioVascular) is a mixture of a hydrophilic biocompatible component that faces the endoluminal surface and a hydrophobic component that is attached to the metal stent surface and serves as a drug reservoir, enabling sustained release of zotarolimus to control neointimal hyperplasia in patients with complex conditions and subgroups of lesions, as shown by encouraging early results.5,6,7,8,9

The purpose of this study, called the Resolute All Comers trial, was to compare the Resolute zotarolimus-eluting stent with an everolimus-eluting stent (Xience V, Abbott Vascular Devices) in an unrestricted, multicenter, open-label, randomized, controlled, noninferiority trial in patients undergoing percutaneous coronary intervention (PCI) in everyday clinical practice.

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