Elsevier

The Lancet

Volume 393, Issue 10175, 9–15 March 2019, Pages 987-997
The Lancet

Articles
Safety and efficacy of a sirolimus-eluting coronary stent with ultra-thin strut for treatment of atherosclerotic lesions (TALENT): a prospective multicentre randomised controlled trial

https://doi.org/10.1016/S0140-6736(18)32467-XGet rights and content

Summary

Background

Supraflex is a sirolimus-eluting stent with a biodegradable polymer coating and ultra-thin struts. We aimed to compare Supraflex with the standard of care, Xience, an everolimus-eluting stent with a durable polymer coating, regarding clinical outcomes with a randomised trial in an all-comer population.

Methods

We did a prospective, randomised, single-blind, multicentre study (TALENT) across 23 centres in Europe (the Netherlands, Poland, the UK, Spain, Bulgaria, Hungary, and Italy). Eligible participants were aged 18 years or older, had one or more coronary artery stenosis of 50% or greater in a native coronary artery, saphenous venous graft, or arterial bypass conduit, and had a reference vessel diameter of 2·25–4·50 mm. Patients underwent percutaneous coronary intervention in an all-comer manner. We randomly assigned patients (1:1) to implantation of either a sirolimus-eluting stent with a biodegradable polymer coating and ultra-thin struts (Supraflex) or an everolimus-eluting stent with a durable polymer coating (Xience). Randomisation was done by local investigators by use of a web-based software with random blocks according to centre. The primary endpoint was a non-inferiority comparison of a device-oriented composite endpoint—cardiac death, target-vessel myocardial infarction, or clinically indicated target lesion revascularisation—between groups at 12 months after the procedure, assessed in an intention-to-treat population. On assumption of 1-year composite endpoint prevalence of 8·3%, a margin of 4·0% was defined for non-inferiority of the Supraflex group compared with the Xience group. This trial is registered with ClinicalTrials.gov, number NCT02870140.

Findings

Between Oct 21, 2016, and July 3, 2017, 1435 patients with 1046 lesions were randomly assigned to Supraflex, of whom 720 received the index procedure, and 715 patients with 1030 lesions were assigned to Xience, all receiving the index procedure. At 12 months, the primary endpoint had occurred in 35 patients (4·9 %) in the Supraflex group and in 37 patients (5·3%) in the Xience group (absolute difference −0·3% [one-sided 95% upper confidence bound 1·6%], pnon-inferiority<0·0001). Definite or probable stent thrombosis prevalence, a safety indicator, was low in both groups and did not differ between them.

Interpretation

The Supraflex stent was non-inferior to the Xience stent for a device-oriented composite clinical endpoint at 12 months in an all-comer population. Supraflex seems a safe and effective alternative drug-eluting stent to other stents in clinical practice.

Funding

European Cardiovascular Research Institute.

Introduction

The evolution of coronary stent technologies has led to reduced adverse outcomes in patients who undergo percutaneous coronary intervention. These technological developments stem from reductions in strut and polymer thickness, improvements in metal alloys and biocompatibility of coating, and optimisation of the kinetics of drug release. The second generation of drug-eluting stents was introduced with thin struts (80–90 μm), new antiproliferative drugs with better elution profiles, and biocompatible polymers. These new stents had lower rates of restenosis coupled with adequate strut coverage,1, 2 resulting in significantly lower rates of thrombotic complications compared with those of first-generation, drug-eluting stents and bare metal stents.3, 4 Subsequently, biodegradable polymers were developed to disappear after drug release, thereby leaving a bare metal stent-like platform. The efficacy of drug-eluting stents with biodegradable polymer coating was shown to be non-inferior to that of stents with durable polymer coating in several studies.5, 6, 7 A study8 published in 2017 showed that a drug-eluting stent with a biodegradable polymer coating and ultra-thin struts was superior to a stent with durable polymer coating, achieving a lower rate of target lesion failure at 12 months than that of the stent with durable coating. Additionally, a meta-analysis9 published in 2018 showed that drug-eluting stents with ultra-thin struts (strut thickness <70 μm) reduced the incidence of target lesion failure compared with that of contemporary stents with thicker struts. Because clinical outcomes of contemporary stents are reaching a safety plateau, it is probable that cost-effectiveness might influence the decision on which stent to use.

Research in context

Evidence before this study

We searched PubMed and checked the listings of the EuroPCR, European Society of Cardiology, Transcatheter Cardiovascular Therapeutics, and American College of Cardiology conferences for complete reports of clinical studies comparing Supraflex, a sirolimus-eluting coronary stent with biodegradable polymer coating, with any other drug-eluting stents. We used the search terms “Supraflex” AND “all-comers” for reports published in English up to Aug 29, 2018. We identified one multicentre, single-group, observational registry—the FLEX Registry. At 12 months, the primary device-oriented composite endpoint occurred in 36 (3·7%) of 980 patients who received Supraflex implantation. However, this registry, which had site-reported events without central adjudication, was a non-randomised trial.

Added value of this study

To our knowledge, this is the first randomised trial with a clinical primary endpoint comparing Supraflex with a contemporary drug-eluting stent in an all-comer population. The Supraflex stent was non-inferior to Xience, an everolimus-eluting stent with durable polymer coating, for the device-oriented composite endpoint of cardiac death, target-vessel myocardial infarction, or clinically indicated target lesion revascularisation at 12 months. Per-protocol analysis showed a significantly lower clinically indicated target lesion revascularisation in the Supraflex group than in the Xience group.

Implications of all the available evidence

The sirolimus-eluting Supraflex coronary stent with absorbable polymer coating was non-inferior to a currently best-in-class drug-eluting stent at 12 months and further benefits might emerge in long-term follow-up.

The Supraflex is a sirolimus-eluting coronary stent made with a cobalt chromium alloy that has a biodegradable polymer technology and an ultra-thin strut thickness of 60 μm. With this stent, the drug is released over a short period of 48 days. Provided that clinical outcomes are comparable with market-leading stents, the introduction of Supraflex in the European market will increase competition and might drive down health-care costs.10 In the FLEX-Registry,11 Supraflex showed a low incidence of major adverse cardiac events at 12 months of follow-up (3·7%) and excellent strut coverage at 6 months of follow-up in 995 unselected real-world patients. Although the ultra-thin strut stent with biodegradable polymer might have an important role in patients' outcomes,7 the Supraflex has not yet been tested in the context of a randomised clinical trial.

We therefore did a trial to investigate non-inferiority of clinical outcomes after implantation of the Supraflex stent compared with the standard of care for atherosclerotic lesions (Xience, an everolimus-eluting stent with durable polymer coating) in broad patient and lesion scenarios from an all-comer European population.

Section snippets

Study design and participants

The TALENT trial was a prospective, randomised, controlled, single-blind, multicentre study in an all-comers population across 23 hospitals or specialised centres in Europe (the Netherlands, Poland, the UK, Spain, Bulgaria, Hungary, and Italy). There were few inclusion and exclusion criteria (appendix).12 Briefly, patients aged at least 18 years, with one or more coronary artery stenosis of 50% or greater in a native coronary artery, saphenous venous graft, or arterial bypass conduit with a

Results

Between Oct 21, 2016 and July 3, 2017, we randomly assigned 1435 patients with a total of 2076 lesions to either the Supraflex group (720 patients with 1046 lesions) or the Xience group (715 patients with 1030 lesions; figure 1). Five patients in the Supraflex group did not undergo percutaneous coronary intervention. 11 patients (1·5%) in the Supraflex group and seven patients (1·0%) in the Xience group withdrew consent within 12 months of the procedure. Baseline clinical characteristics were

Discussion

In the TALENT study, we showed that Supraflex, a sirolimus-eluting coronary stent with biodegradable polymer coating and ultra-thin struts, was non-inferior to the standard of care, an everolimus-eluting stent with durable polymer coating, for a device-oriented composite endpoint of cardiac death, target-vessel myocardial infarction, or clinically indicated target lesion revascularisation at 12 months, in an all-comer European population.

Although device success was high in our study, we found a

Data sharing

All data, including study participant data, data dictionary, statistical analysis plan, and informed consent, will not be shared. The protocol is available online.

References (26)

Cited by (64)

  • Rationale and design of the TUXEDO-2 India study: Ultra-Thin strUt Supraflex Cruz versus XiencE in a Diabetic pOpulation with multi-vessel disease–2

    2023, American Heart Journal
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    In the TALENT randomized-controlled trial (RCT), Supraflex (ultra-thin strut biodegradable polymer-coated) DES was found to be non-inferior to the widely used Xience (durable polymer-coated) DES for a device-oriented composite endpoint in an all-comer population (4.9% vs 5.3%: p for non-inferiority ≤.001). Of interest, the per-protocol analysis showed a significantly lower one-year rate of clinically-indicated target lesion revascularization in the Supraflex group compared to the Xience group (1.2% vs 3.1%; p=.021).15,16 Supraflex Cruz is the next-generation Supraflex stent, approved by the Drugs Controller General of India (DCGI) and has received CE mark certification from the European Union.

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