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Randomized Controlled Trial
. 2025 Jun 3;14(11):e039482.
doi: 10.1161/JAHA.124.039482. Epub 2025 May 22.

Safety and Efficacy of Cobalt Chromium Everolimus-Eluting Stents for Treatment of In-Stent Restenosis: An ILUMIEN IV Substudy

Affiliations
Randomized Controlled Trial

Safety and Efficacy of Cobalt Chromium Everolimus-Eluting Stents for Treatment of In-Stent Restenosis: An ILUMIEN IV Substudy

Ziad A Ali et al. J Am Heart Assoc. .

Abstract

Background: The optimal management strategy for in-stent restenosis (ISR) remains unclear. We aimed to determine the safety and efficacy of percutaneous coronary intervention with XIENCE cobalt chromium everolimus-eluting stents (EES) for treatment of ISR.

Methods: In the ILUMIEN IV (Optical Coherence Tomography Guided Coronary Stent Implantation Compared to Angiography: A Multicenter Randomized Trial in Percutaneous Coronary Intervention) trial, the 1-year outcomes of all randomized patients with a single diffuse or multifocal single-layer ISR lesion treated with EES were compared with a performance goal. The primary end point was target lesion failure, the composite of cardiac death, target vessel-myocardial infarction, or ischemia-driven target lesion revascularization. Outcomes in patients with a single EES-treated ISR and non-ISR lesion were also compared.

Results: From May 2018 through December 2020, 247 patients with a single ISR lesion were treated with EES. Target lesion failure at 1 year occurred in 18 patients (7.4% [upper 1-sided 97.5% CI, 11.5%]), which was lower than the predefined performance goal of 20% (P<0.001). Compared with non-ISR lesions treated with EES (n=2021), the postpercutaneous coronary intervention minimal stent area by optical coherence tomography was smaller in treated ISR lesions (5.0±1.8 mm2 versus 5.6±1.9 mm2; P<0.001), but minimum stent expansion was similar (78.8±18.0% versus 79.0±16.9%; P=0.87), as was 1-year target lesion failure (7.4% versus 4.7%; hazard ratio, 1.58 [95% CI, 0.95-2.61]; P=0.07).

Conclusions: XIENCE EES was safe and effective for treatment of single-layer ISR. Compared with non-ISR lesions, ISR lesions treated with EES had a smaller postpercutaneous coronary intervention minimal stent area although stent expansion and 1-year target lesion failure rates were not different.

Registration: URL: https://clinicaltrials.gov/; Unique identifier: NCT03507777.

Keywords: drug‐eluting stent; in‐stent restenosis; percutaneous coronary intervention.

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Conflict of interest statement

Z.A. Ali reports institutional grants from Abbott, Abiomed, Acist Medical, Boston Scientific, Cardiovascular Systems Inc, Medtronic, Opsens Medical, Philips. Shockwave Medical; personal fees from Amgen, Astra Zeneca, Boston Scientific; equity from Elucid, Lifelink, Spectrawave, Shockwave and Vital Connect. U. Landmesser reports receiving lecture fees and advisory fees from AstraZeneca, Amgen, and Sanofi, and grant support, lecture fees, or advisory fees from Abbott and Novartis. A. Maehara consultant for Boston Scientific, received speaker honoraria from Nipro, and is on the adversary board of SpectraWAVE. M. Matsumura is a consultant for TERUMO and Boston Scientific. E. Shlofmitz has been a consultant to Abbott Vascular, ACIST Medical, Boston Scientific, Gentuity, Philips, RadiAction, Shockwave Medical and Terumo. Y. S. Abdelwahed reports receiving lecture fees and advisory fees from Boston Scientific and Shockwave. P. Canova is a consultant for Abbott Vascular and Boston Scientific; and has received grants from Amarin Pharma Inc, Amgen, Bristol Myers Squibb Company, Daiichi‐Sankyo, Sanofi, and Terumo. N. Gonzalo has received a research grant from Abbott; and consultancy and speaker fees from Abbott, Boston Scientific, Shockwave Medical, Abiomed, and Philips. K.N. Fall is a consultant for Abbott, Boston Scientific, and Conavi. R.J. McGreevy, R.W. McNutt, H. Nie, J. Wang and J. Buccola are employees of Abbott Vascular. G.W. Stone has received speaker honoraria from Medtronic, Pulnovo, Infraredx, Abiomed, and Abbott; has served as a consultant to Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Cardiomech, Gore, Amgen, Adona Medical, and Millennia Biopharma; and has equity/options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, and Valfix, Xenter. Dr Stone's daughter is an employee at IQVIA. Institutional disclosure: Dr Stone's employer, Mount Sinai Hospital, receives research support from Abbott, Abiomed, Bioventrix, Cardiovascular Systems, Inc, Phillips, Biosense Webster, Shockwave, Vascular Dynamics, Pulnovo, and V‐Wave. The other authors report nothing to disclose relevant to the article.

Figures

Figure 1
Figure 1. One‐year clinical outcomes in ISR.
A, One‐year TLF (composite of cardiac death, target‐vessel myocardial infarction, or ischemia driven target lesion revascularization) and (B) secondary clinical end points after ISR PCI are presented. ID‐TLR indicates ischemia driven target‐lesion revascularization; ISR, in‐stent restenosis; PCI, percutaneous coronary intervention; TLF, target‐lesion failure; and TV‐MI, target‐vessel myocardial infarction.
Figure 2
Figure 2. Comparison of 1‐year clinical outcomes between ISR and non‐ISR.
One‐year TLF (composite of cardiac death, target‐vessel myocardial infarction, or ischemia driven target lesion revascularization) using (A) modified ARC‐2 definition and (B) SCAI definition of periprocedural MI are compared between patients with and without ISR undergoing PCI. ARC indicates the Academic Research Consortium; HR, hazard ratio; ISR, in‐stent restenosis; MI, myocardial infarction; PCI, percutaneous coronary intervention; SCAI, the Society for Cardiovascular Angiography and Intervention; and TLF, target lesion failure.

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