Fast track — ArticlesEfficacy and safety of zotarolimus-eluting and sirolimus-eluting coronary stents in routine clinical care (SORT OUT III): a randomised controlled superiority trial
Introduction
Introduction of sirolimus and paclitaxel drug-eluting stents more than halved the need for new revascularisations after implantation of coronary artery stents.1, 2, 3, 4, 5, 6 However, the safety of these first-generation drug-eluting stents was questioned after reports of their association with an increased risk of late and very late stent thrombosis.4, 7 This risk might be explained by insufficient healing of the vessel wall caused by delayed neointimal stent coverage, and by late-acquired incomplete stent apposition associated with inflammation and late remodelling, leaving naked stent struts as a nidus for thrombotic events.8, 9, 10 Whether adverse vessel wall reactions to implantation of drug-eluting stents are related to the type of drug eluted from the stent or to the polymer coating of the stent is unknown.8, 9, 10
Such safety concerns led to recommendations for long-term dual antiplatelet therapy after implantation of drug-eluting stents.11 In this context, the second-generation zotarolimus-eluting stent seemed to be a safer alternative to sirolimus-eluting and paclitaxel-eluting stents. The zotarolimus-eluting stent induced uniform and complete neointimal coverage of the stent struts, and was associated with a reduced occurrence of late-acquired incomplete stent apposition.12, 13 Also, the polymer phosphorylcholine coating used for drug elution from the zotarolimus-eluting stent is a synthetic copy of the predominant phospholipid in the outer membrane of red blood cells and seemed to be a safer, non-inflammatory alternative to the polymers used for sirolimus-eluting and paclitaxel-eluting stents.14
Findings from the first randomised trials generated optimism regarding the clinical effectiveness of the zotarolimus-eluting stent.15, 16, 17 However, these trials were restricted to patients with a single artery stenosis, excluded complex lesions such as bifurcation lesions and chronic total occlusions, were limited by angiographic inclusion criteria, excluded patients with recent myocardial infarction, and were powered to assess only angiographic late lumen loss or target vessel failure.15, 16, 17 We therefore aimed to compare the efficacy and safety (defined by cardiac death, myocardial infarction, and stent thrombosis) of the zotarolimus-eluting stent versus the extensively used and validated sirolimus-eluting stent in a routine clinical setting with no direct follow-up.
Section snippets
Patients and study design
Within the framework of the Danish Organisation for Randomised Trials with Clinical Outcome (SORT OUT), we undertook a multicentre, single-blind, randomised, all-comer trial between January, 2006, and August, 2007, in five Danish high-volume percutaneous coronary intervention centres.18 We used data from Danish health-care registries to compare patients who were eligible for randomisation but were and were not randomly allocated to treatment during the study period to allow us to report the
Results
Figure 1 shows the trial profile. Of 9221 patients who were screened, 3545 (38%) were excluded, 3344 (36%) were eligible for randomisation but were excluded, and 2332 (25%) with 3230 lesions were randomly assigned to receive zotarolimus-eluting or sirolimus-eluting stents. Overall, six patients were lost to follow-up because they emigrated. The randomly allocated stent was implanted in 1589 (98%) lesions allocated to the zotarolimus-eluting stent and 1569 (97%) lesions allocated to
Discussion
We have shown that in routine clinical care, patients receiving the zotarolimus-eluting stent had significantly more major adverse cardiac events in 9 months than did those treated with the sirolimus-eluting stent. During 9–18 months, the sirolimus-eluting stent remained superior to the zotarolimus-eluting stent for occurrence of major adverse cardiac events, myocardial infarction, and target vessel revascularisation. Deliverability was similar for both stents.
By contrast with previously
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