Elsevier

The Lancet

Volume 385, Issue 9977, 18–24 April 2015, Pages 1527-1535
The Lancet

Articles
Zotarolimus-eluting durable-polymer-coated stent versus a biolimus-eluting biodegradable-polymer-coated stent in unselected patients undergoing percutaneous coronary intervention (SORT OUT VI): a randomised non-inferiority trial

https://doi.org/10.1016/S0140-6736(14)61794-3Get rights and content

Summary

Background

New-generation drug-eluting coronary stents have reduced the risk of coronary events, especially in patients with complex disease or lesions. To what extent different stent platforms, polymers, and antiproliferative drugs affect outcomes, however, is unclear. We investigated the safety and efficacy of a third-generation stent by comparing a highly biocompatible durable-polymer-coated zotarolimus-eluting stent with a biodegradable-polymer-coated biolimus-eluting stent.

Methods

This open-label, randomised, multicentre, non-inferiority trial was done at three sites across western Denmark. All patients who presented with stable coronary artery disease or acute coronary syndromes and at least one coronary artery lesion (more than 50% stenosis) from March, 2011, to August, 2012, were assessed for eligibility. Patients were randomly assigned in a 1:1 ratio to receive either the durable-polymer zotarolimus-eluting stent or the biodegradable-polymer biolimus-eluting stent. The primary endpoint was a composite of safety (cardiac death and myocardial infarction not clearly attributable to a non-target lesion) and efficacy (target-lesion revascularisation) at 12 months, analysed by intention to treat. The trial was powered to assess non-inferiority of durable-polymer zotarolimus-eluting stent compared with the biodegradable-polymer biolimus-eluting stent with a predetermined non-inferiority margin of 0·025. This trial is registered with ClinicalTrials.gov, number NCT01956448.

Findings

Of 7103 screened, 1502 patients with 1883 lesions were assigned to receive the durable-polymer zotarolimus-eluting stent and 1497 patients with 1791 lesions to receive the biodegradable-polymer biolimus-eluting stent. 79 (5·3%) and 75 (5·0%) patients, respectively, met the primary endpoint (absolute risk difference 0·0025, upper limit of one-sided 95% CI 0·016%; p=0·004). The individual components of the primary endpoint did not differ significantly between stent types at 12 months.

Interpretation

The durable-polymer-coated zotarolimus-eluting stent was non-inferior to the biodegradable-polymer-coated biolimus-eluting stent in unselected patients.

Funding

Medtronic Cardiovascular and Biosensors Interventional Technologies.

Introduction

The introduction of drug-eluting stents (DES) consisting of a metal platform and a polymer surface with controlled release of antiproliferative agents has reduced the incidence of restenosis and the need for target-vessel revascularisation compared with bare-metal stents (BMS).1, 2, 3 First-generation DES with durable polymers, however, were associated with increased risk of stent thrombosis, especially very late after discontinuation of dual antiplatelet therapy.4, 5 Remnants of polymer material after drug release is completed are potential triggers for chronic inflammatory responses that can lead to impaired endothelialisation of the stent strut and positive vessel remodelling, and increase the risk of stent thrombosis.6, 7 These findings drove the development of DES with biocompatible durable polymers to lower the risk of inflammation, or of biodegradable polymers that are eventually absorbed and render stent surfaces similar to those of BMS. Durable-polymer-coated DES have been thoroughly investigated in clinical trials.8, 9, 10, 11, 12, 13, 14 Few studies, however, have compared those coated with durable polymers and biodegradable polymers, and most that have been compared have released only everolimus or sirolimus.15, 16, 17, 18, 19, 20, 21 Meta-analyses suggest that new-generation DES coated with biocompatible durable polymers and biodegradable polymers have similar safety and efficacy.22, 23, 24, 25 The Scandinavian Organization for Randomized Trials with Clinical Outcome (SORT OUT) VI trial was a non-inferiority trial done to investigate the safety and efficacy of each type of stent eluting, respectively, zotarolimus and biolimus.

Section snippets

Study design and patients

SORT OUT VI was an open-label, randomised, multicentre, non-inferiority trial done at three university hospitals across western Denmark. All patients who presented with stable coronary artery disease or acute coronary syndromes, including myocardial infarction with or without ST-segment elevation, and at least one coronary lesion with more than 50% stenosis in a vessel with a diameter of 2·25–4·00 mm between March, 2011, and August, 2012, were screened for eligibility. No restrictions were

Results

We screened 7103 patients and randomly assigned 2999 patients with 3674 lesions to receive either the durable-polymer zotarolimus-eluting stent (1502 patients with 1883 lesions) or the biodegradable-polymer biolimus-eluting stent (1497 patients with 1791 lesions; figure 1). Baseline demographic and clinical characteristics in the two study groups were well balanced except for previous PCI, number of lesions per patient, and lesion length (table 1). High proportions of patients in the two stent

Discussion

This head-to-head comparison showed non-inferiority of the durable-polymer zotarolimus-eluting stent compared with the biodegradable-polymer biolimus-eluting stent in unselected patients. Excellent outcomes were seen for both stent types in relation to definite stent thrombosis, which is important in view of the complexity of disease, including a high rate of acute coronary syndromes, in our trial population.

Our event rates for the primary endpoint in patients who received the durable-polymer

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