Randomised comparison of the polymer-free biolimus-coated BioFreedom stent with the ultrathin strut biodegradable polymer sirolimus-eluting Orsiro stent in an all-comers population treated with PCI: the SORT OUT IX Trial
Selected in Circulation by D. Giacoppo
While investigations testing differences in efficacy and safety between drug-eluting stents according to the characteristics of the coating – durable, bioresorbable, or polymer-free – have shown mixed results, several studies have highlighted the benefit of implanting a device with thinner strut.
References
Authors
Lisette Okkels Jensen , Michael Maeng , Bent Raungaard , Johnny Kahlert , Julia Ellert , Lars Jakobsen , Anton Boel Villadsen , Karsten Tange Veien , Steen Dalby Kristensen , Ole Ahlehoff , Steen Carstensen , Martin Kirk Christensen , Christian Juhl Terkelsen , Thomas Engstroem , Knud Nørregaard Hansen , Hans Erik Bøtker , Jens Aaroe , Troels Thim , Leif Thuesen , Philip Freeman , Ahmed Aziz , Ashkan Eftekhari , Anders Junker , Svend Eggert Jensen , Jens Flensted Lassen , Henrik Steen Hansen , Evald Høj Christiansen and The Sort Out IX Study Group
Reference
Circulation 2020;141:2052-2063. doi: 10.1161/CIRCULATIONAHA.119.040241.
Published
May 2020
Link
Read the abstractReviewer
My Comment
Why this study? – the rationale/objective
Drug-eluting stents with highly biocompatible durable polymers, fully bioresorbable polymers, or polymer-free coatings have been developed to reduce adverse events after percutaneous coronary intervention (PCI). However, relative benefits in terms of long-term clinical outcomes among these different technical features are still unclear.
The polymer-free biolimus-eluting BioFreedom stent has shown superior safety and efficacy compared with a bare-metal stent, despite the use of only 1 month of DAPT after PCI. Some recent trials comparing the thin-strut bioresorbable-polymer sirolimus-eluting Orsiro stent with a durable-polymer drug-eluting stent have shown excellent results in different subsets.
The SORT OUT IX trial sought to assess whether the polymer-free BioFreedom stent is non-inferior to the thin-strut bioresorbable polymer Orsiro stent.
How was it executed? – the methodology
The SORT OUT IX was a multicentre, all-comers, single-blind, registry-based, randomized clinical trial designed to demonstrate the non-inferiority of the BioFreedom stent compared with the Orsiro stent. The primary endpoint was a composite of major adverse cardiovascular events including cardiac death, target lesion-related myocardial infarction, or target lesion revascularisation.
Periprocedural anticoagulation and antithrombotic therapy composition were left at operator’s discretion. Dual antiplatelet therapy was recommended for 6 months in stable coronary artery disease and for 12 months in acute coronary syndrome.
Outcomes at 12 months were assessed by intersecting data collected in national Danish health care and administrative registries. An independent clinical event committee reviewed all source documents retrieved by registries to adjudicate clinical endpoints. Angiographic recordings were independently reviewed at each participating centre to assess stent thrombosis type, target lesion revascularisation, and target vessel revascularisation.
What is the main result?
Between December 2015 and April 2017, a total of 3151 undergoing PCI were randomly assigned to the BioFreedom stent (1572 patients, 1966 lesions) or the Orsiro stent (1579 patients, 1985 lesions).
Study population had mean age of 66 years, included prevalently men (77%), and showed 19% of diabetes, 15% of prior myocardial infarction, 21% of prior PCI, and 8% of prior coronary artery bypass grafting. Clinical presentation was stable angina in 42% of patients, unstable angina or non-ST-segment elevation myocardial infarction (NSTEMI) in 29%, ST-segment elevation myocardial infarction (STEMI) in 24%; the remaining patients were admitted for other reason. The number of target lesions per patient was 1.2 ± 0.6, with more than three-quarters of patients presenting with single-vessel disease, and median lesion length was 16 [12-24] mm.
Stent delivery failure rate was similar between the BioFreedom and Orsiro groups (2.3% vs. 2.0%, p=0.48).
At 30 days, target vessel revascularisation was more frequent in the Orsiro group (1.0% vs. 2.0%; incidence rate ratio [IRR] 0.51, 95% CI 0.28-0.94), while differences in the other endpoints were largely non-significant.
At 12 months, the primary composite endpoint of major adverse cardiovascular events occurred in 79 patients (5.0%) assigned to the BioFreedom stent and 59 (3.7%) patients assigned to the Orsiro stent (IRR 1.34, 95% CI 0.96-1.89). Non-inferiority of the BioFreedom stent to the Orsiro stent was not met (p=0.14).
No significant differences were observed between the BioFreedom and Orsiro groups in terms of all-cause death (2.0% vs. 2.7%, IRR 0.72, 95% CI 0.45-1.14), target lesion-related myocardial infarction (1.7% vs. 1.6%, IRR 1.00, 95% CI 0.58-1.72), any myocardial infarction (2.4% vs. 2.5%, IRR 0.92, 95% CI 0.59-1.45), definite/probable stent thrombosis (1.0% vs. 1.1%; IRR 0.89, 95% CI 0.45-1.74), and cardiac death (1.0% vs. 1.8%, IRR 0.55, 95% CI 0.30-1.02), though the latter endpoint showed an evident numerical imbalance (p=0.056) in the distribution of events between groups. Patients in the BioFreedom group experienced more frequently target lesion revascularisation compared with the Orsiro group (3.5% vs. 1.3%; IRR 2.77, 95% CI 1.66-4.62), while difference in target vessel revascularisation was not statistically significant (4.8% vs. 3.5%; IRR 1.35, 95% CI 0.96-1.92). Subgroup analyses with respect to age, gender, diabetes, previous myocardial infarction, previous PCI, left anterior descending target lesion, multivessel disease, multiple-stent PCI, acute coronary syndrome, and STEMI did not reveal inconsistency in terms of the primary endpoint.
Critical reading and the relevance for clinical practice
The SORT OUT IX trial was inconclusive with respect to the primary study hypothesis of non-inferiority of the BioFreedom stent compared with the Orsiro stent. However, the absolute difference of 1.29% in major adverse cardiovascular events between groups did not even translate in a statistically significant superiority of the Orsiro stent over the BioFreedom stent (p=0.09). The numerical excess of major adverse cardiac events observed between groups was mainly driven by target lesion revascularisation, which resulted to be more than two times higher in patients assigned to the BioFreedom stent compared with those assigned to the Orsiro stent (p=0.0001).
In the SORT OUT IX trial, the different incidence of target lesion revascularisation observed between treatment groups should be considered in light of the technical specifications of the two drug-eluting stents tested. The BioFreedom is a biolimus-coated (15.6 μg/mm2, elution completed in 1 month), polymer-free, stainless steel stent with strut thickness of 120 μm. The Orsiro is a sirolimus-eluting (1.4 μg/mm2, elution completed in 12-14 weeks), fully bioresorbable poly-L-lactic acid polymer (abluminal thickness of 3.5 μm), cobalt-chromium stent with strut thickness of 60 μm (2.25 to 3.00 mm diameters) or 80 μm (3.50 and 4.00 mm diameters).
While investigations testing differences in efficacy and safety between drug-eluting stents according to the characteristics of the coating – durable, bioresorbable, or polymer-free – have shown mixed results, several studies have highlighted the benefit of implanting a device with thinner strut.
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