Elsevier

The Lancet

Volume 383, Issue 9915, 1–7 February 2014, Pages 413-423
The Lancet

Articles
Third-generation zotarolimus-eluting and everolimus-eluting stents in all-comer patients requiring a percutaneous coronary intervention (DUTCH PEERS): a randomised, single-blind, multicentre, non-inferiority trial

https://doi.org/10.1016/S0140-6736(13)62037-1Get rights and content

Summary

Background

Third-generation, permanent-polymer-based drug-eluting stents with novel, flexible designs might be more easily delivered than previous generations of stents in complex coronary lesions, but might be less longitudinally stable. We aimed to assess the safety and efficacy in all-comer patients of two third-generation stents that are often used clinically, but that have not yet been compared, and one of which has not previously been assessed in a randomised trial.

Methods

In this investigator-initiated, single-blind, multicentre, randomised, two-arm, non-inferiority trial, patients aged 18 years and older who required a percutaneous coronary intervention with implantation of a drug-eluting stent were recruited from four study sites in the Netherlands. We randomly assigned patients by independently managed computer-generated allocation sequences in a 1:1 ratio to receive either cobalt-chromium-based zotarolimus-eluting stents (Resolute Integrity, Medtronic, Santa Rosa, CA, USA) or platinum-chromium-based everolimus-eluting stents (Promus Element, Boston Scientific, Natick, MA, USA). Patients and analysts were masked to the allocated stent, but treating clinicians were not. The primary endpoint of target-vessel failure was a composite of safety (cardiac death or target-vessel-related myocardial infarction) and efficacy (target-vessel revascularisation) at 12 months, analysed by intention to treat (with a non-inferiority margin of 3·6%). This trial is registered with ClinicalTrials.gov, number NCT01331707.

Findings

Between Nov 25, 2010, and May 24, 2012, 1811 eligible all-comer patients, with 2371 target lesions, were enrolled in the study. 370 (20%) patients presented with ST-elevation myocardial infarction and 447 (25%) with non-ST-elevation myocardial infarction. 906 patients were assigned to receive zotarolimus-eluting stents and 905 to receive everolimus-eluting stents. Ease of stent delivery was shown by very low numbers of patients requiring treatment other than their assigned study treatment (six [1%] in the zotarolimus-eluting stent group vs five [1%] in the everolimus-eluting stent group; p=0·22). 12-month follow-up results were available for 1810 patients (one patient in the zotarolimus-eluting stent group withdrew consent). The primary endpoint was met by 55 (6%) of 905 patients in the zotarolimus-eluting stent group and 47 (5%) of 905 in the everolimus-eluting stent group. The zotarolimus-eluting stent was non-inferior to the everolimus-eluting stent (absolute risk difference 0·88%, 95% CI −1·24% to 3·01%; upper limit of one-sided 95% CI 2·69%; non-inferiority p=0·006). We noted no significant between-group differences in individual components of the primary endpoint. Definite stent thrombosis occurred in three (0·3%) patients in the zotarolimus-eluting stent group and six (0·7%) patients in the everolimus-eluting stent group (p=0·34). Longitudinal stent deformation was seen only in the everolimus-eluting stent group (nine [1·0%] of 905 vs 0 of 906, p=0·002; nine of 1591 [0·6%] everolimus-eluting stents implanted became deformed), but was not associated with any adverse events.

Interpretation

Both stents were similarly efficacious and safe, and provided excellent clinical outcomes, especially in view of the large number of patients who presented with acute myocardial infarctions.

Funding

Boston Scientific, Medtronic.

Introduction

Drug-eluting stents that counteract the development of restenosis by delivering antiproliferative drugs from polymer-based coatings have revolutionised the percutaneous treatment of obstructive coronary artery disease.1, 2 First-generation durable-polymer drug-eluting stents were made from bare-metal stent platforms with little flexibility and fairly plain permanent-polymer coatings, which were associated with an increased risk of late and very late stent thrombosis.3, 4 Second-generation drug-eluting stents with durable coatings that were more biocompatible than those of first-generation stents were then developed. These newer stents showed superior safety profiles in various clinical settings.5, 6, 7, 8, 9

Most recently, third-generation, durable-polymer-based drug-eluting stents were developed to answer the demand for more flexible and highly deliverable devices that can tackle very challenging coronary lesion and vessel anatomies, as are increasingly encountered in ageing western patient populations. Although the coatings of these stents contain the same established drug and durable polymer combinations as their second-generation counterparts, the design and material of their bare-metal stent platforms have been changed substantially.10, 11, 12, 13, 14 However, such changes might have the trade-off of reducing longitudinal stent stability,15, 16 which would account for the occurrence of longitudinal stent deformation that has been reported after contact between deployed stents and guiding catheters, balloon catheters, or other catheter-based devices.16, 17, 18, 19 Data so far reported about the incidence and clinical significance of longitudinal stent deformation have been conflicting.16, 17, 18, 19

A cobalt-chromium-based zotarolimus-eluting stent, made from a single sinusoidal-formed wire (Resolute Integrity, Medtronic, Santa Rosa, CA, USA), and a laser-cut platinum-chromium-based everolimus-eluting stent (Promus Element, Boston Scientific, Natick, MA, USA), are two such third-generation drug-eluting stents.11, 12, 13, 14 Although clinical outcome data for the use of the Promus Element stent in patients with mild-to-moderate clinical risk have been reported,11, 19 no such data are available for the Resolute Integrity stent. We aimed to compare clinical outcomes from the use of these two third-generation drug-eluting stents in a broad population of all-comer patients.

Section snippets

Study design and patients

We undertook a randomised trial entitled DUrable polymer-based sTent CHallenge of Promus ElemEnt versus ReSolute integrity (DUTCH PEERS): randomized multicenter trial in all comers population Treated Within Eastern NeThErlands II (TWENTE II) at four Dutch centres (Thoraxcentrum Twente, Medisch Spectrum Twente, Enschede; Rijnstate Hospital, Arnhem; Scheper Hospital, Emmen; and Medisch Centrum Alkmaar, Alkmaar). In this investigator-initiated, single-blind, multicentre, randomised, two-arm,

Results

Between Nov 25, 2010, and May 24, 2012, 1811 eligible all-comer patients, aged 21–91 years, with 2371 target lesions, were enrolled and randomly assigned to treatment with third-generation zotarolimus-eluting Resolute Integrity stents (906 patients, 1205 lesions) or everolimus-eluting Promus Element stents (905 patients, 1166 lesions; figure 1). One patient from the zotarolimus-eluting stent group withdrew consent after 1 day; therefore, baseline data and interventional results are reported for

Discussion

DUTCH PEERS is the first randomised comparison of the third-generation zotarolimus-eluting Resolute Integrity and everolimus-eluting Promus Element stents. It is also the first trial ever to investigate the Resolute Integrity stent. In this all-comer patient population, no significant difference was seen between stent groups in the primary endpoint of target-vessel failure at 12-month follow-up. As a result, the zotarolimus-eluting Resolute Integrity stent met the criterion of non-inferiority

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