Sirolimus-Eluting Balloon With Provisional Stenting Versus Systematic Drug-Eluting Stent Implantation to Treat De Novo Coronary Lesions: A Randomized, Open-Label, Noninferiority Trial
Abstract
BACKGROUND: Implantation of drug eluting stents (DESs) is currently the default approach for percutaneous coronary interventions, but long-term adverse events still exist. An approach with minimal stenting deserves to be assessed in a randomized trial. We studied a novel sirolimus-eluting balloon (SEB) that elutes sirolimus over a 90-day period using a biodegradable polymer microreservoir technology. METHODS: In a multicenter, open-label, randomized trial, we compared an SEB-based strategy with provisional DES with one of systematic DES for de novo lesions in coronary arteries between 2 and 5 mm in diameter. Subjects were randomized 1:1 before percutaneous coronary intervention. The primary end point was target vessel failure, a composite of cardiac death, target vessel–related myocardial infarction, and clinically driven target vessel revascularization. It was tested for noninferiority at 1 year with the use of an absolute margin equal to 50% of the combined event rate at a significance level of 0.025. The primary analysis population included all randomized subjects with completed or attempted percutaneous revascularization, analyzed according to the intention-to-treat principle. A sensitivity analysis was performed on the per-protocol population. RESULTS: Between August 27, 2021, and July 29, 2024, 3323 participants were randomized and treated in 62 sites. Among 1661 participants in the SEB strategy group, bailout stenting was performed in 343 (20.7%). Target vessel failure occurred over 365 days in 88 (5.3%) and 73 (4.4%) participants in the SEB and the systematic DES strategy groups, respectively (risk difference, 0.91% [95% CI –0.55% to 2.38%]; 1-sided P =0.02 for noninferiority with a 2.44% noninferiority margin). Clinically driven target vessel revascularization occurred more frequently in the SEB strategy group (3.3% versus 2.1%; risk difference, 1.22% [95% CI, 0.11%–2.33%). Safety events, including lesion thrombosis, were low and similar in both groups. Although the results of the per-protocol population (3194 participants, 96%) did not confirm noninferiority (upper boundary of the 95% CI, 2.63; P =0.04), they were similar to the intention-to-treat results in both magnitude and direction. CONCLUSIONS: At 1 year, in the primary intention-to-treat analysis population, a strategy of percutaneous coronary intervention with SEB and provisional DES was noninferior to the systematic use of DES for the primary end point of target vessel failure. The per-protocol population sensitivity analysis did not confirm noninferiority. Clinically driven target vessel revascularization occurred more frequently in the SEB strategy group. At 5 years, target vessel failure will be tested again for noninferiority and for superiority if noninferiority is achieved. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04859985.
Article Details
Authors (82)
Christian Spaulding
Cardiovascular Department, Hôpital Européen Georges-Pompidou, Université Paris-Cité, France (E.P., C.S., E.M.).
Florian Krackhardt
Berlin Institute of Health at Charité Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charité Campus Virchow-Klinikum, Germany (F.K).
Kris Bogaerts
Department of Public Health and Primary Care, I-BioStat, KU Leuven, Leuven and UHasselt, I-BioStat, Hasselt, Belgium (K.B.).
Eltigani Abdelaal
Manchester Heart Institute, Manchester University NHS Foundation Trust, UK (E.A.).
Fernando Alfonso
Department of Cardiology, Hospital Universitario de La Princesa, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria Hospital Universitario de La Princesa, Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBER-CV), Madrid
Carlo Briguori
Mediterranea Cardiocentro, Naples, Italy (C.B.).
Leonhard Bruch
BG Klinikum Unfallkrankenhaus Department of Internal Medicine/Cardiology, Berlin, Germany (L.B.).
Nicholas Cruden
Royal Infirmary of Edinburgh, Edinburgh
Alexander W. Den Hartog
Department of Cardiology, Amsterdam University Medical Center, Netherlands (A.W.D.H.).
Philippe Garot
Institut Cardiovasculaire Paris Sud Hôpital Jacques Cartier Ramsay-Santé, Massy, France (P.G.).
Mathieu Godin
Clinique Saint Hillaire, Rouen, France (M.G.).
David Hildick-Smith
Sussex Cardiac Centre, University Hospitals Sussex, Brighton, United Kingdom
Thomas Johnson
Andrew Ladwiniec
University Hospitals of Leicester NHS Trust, Leicester, United Kingdom
Axel Linke
University Hospital, Dresden, Germany
Clint Anthony Maart
Norfolk and Norwich University Hospital NHS Foundation Trust, Norwich Medical School, University of East Anglia, UK (C.A.M, S.E.).
Kambis Mashayekhi
Clinic of Internal Medicine and Cardiology, Heart Center Lahr, Lahr, Germany
Pascal Meier
Ludovic Meunier
Cardiology Department, Centre Hospitalier La Rochelle, France (L.M.).
Kenneth Morgan
Northern General Hospital, Sheffield, UK (K.P.M.).
Peter O’Kane
Department of Cardiology, Royal Bournemouth Hospital, Bournemouth, United Kingdom
Etienne Puymirat
Université Paris-Cité, Paris
Tuomas T. Rissanen
Heart Center, North Karelia Central Hospital, Siunsote, University of Eastern Finland, Kuopio (T.T.R.).
Manel Sabaté
Cardiology Department, Cardiovascular Institute, Hospital Clinic, Institut d’Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Centro de Investigación Biomédica en Red Enfermedades Cardiovaculares (CIBER-CV), Barcelona
Thomas Schmitz
Gabor G. Toth
Jasper Trevelyan
Worcestershire Acute Hospital NHS Trust, UK (J.T.).
Piotr Wanczura
Department of Cardiology, Collegium Medicum, University of Rzeszow, Poland (P.W.).
Marcus Wiemer
Johannes Wesling Universitätsklinik, Minden, Germany (M.W.).
Joanna J. Wykrzykowska
From the Department of Cardiology, St. Antonius Hospital, Nieuwegein (D.J.G., W.L.B., J.P., B.J.W.M.R., L.T., M.J.S., J.B., V.J.N., D.C.O., J.M.B.), the Department of Cardiology, Amsterdam UMC, Amsterdam (H.M.A., J.G.P.T., R.D.), the Department of Cardiology, University Medical Center Utrecht, Utrecht (H.M.A., M. Voskuil), the Department of Cardiology, Radboud University Medical Center, Nijmegen (M.J.P.R., V.J.N., N.R.), the Department of Cardiology, Maastricht University Medical Center (L.V., A.J.J.I., P.A.V., A.W.J.H.), and Cardiovascular Research Institute Maastricht (L.V., P.A.V., A.W.J.H., J.M.B.), Maastricht, the Department of Cardiology, Leiden University Medical Center, Leiden (F.K., J.M.M.-C.), the Department of Cardiology, University Medical Center Groningen, Groningen (K.H.B., J.J.W.), the Department of Cardiology, Erasmus University Medical Center, Rotterdam (N.M.V.M.), the Department of Cardiology, Haga Hospital, the Hague (C.E.S.), the Department of Cardiology, Amphia Hospital, Breda (A.J.J.I...
Philip Urban
Cardiovascular Department, Hôpital de la Tour, Geneva, Switzerland (P.U.).
Simon Eccleshall
Norfolk and Norwich University Hospital NHS Foundation Trust, Norwich Medical School, University of East Anglia, UK (C.A.M, S.E.).
Mathias Frick
Clemens Steinwender
Leoš Pleva
Martin Poloczek
Guillaume Cayla
Cardiology Department, Nimes University Hospital, Montpellier University, ACTION Study Group, Nimes, France
Nicolas Delarche
Pierre Poustis
Martin Andrassy
Ralf Birkemeyer
Fabian Brunner
Frank Edelmann
Marcel Halbach
Christoph Langer
Faridun Daniel Rahimi Nedjat
Joachim Schofer
Bastian Wein
Dario Bongiovanni
Maurizio d’Amico
Fabrizio Ugo
Michael Dickinson
Madera Cambero
Kamil Skoczynski
Fam Jiang Ming
Victor A. Jimenez Diaz
Diego Arroyo
Jonas Häner
Juan Fernando Iglesias
Gregor Leibundgut
Johannes Rigger
Barbara Stähli
Freidoon Keshavarzi
Nick Cruden
Nick Curzen
University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom
Karim Ratib
Royal Stoke University Hospital, Stoke-on-Trent, United Kingdom
Neil Ruparelia
Andrew Peter Vanezis
Stuart Watkins
NHS Golden Jubilee, Glasgow, United Kingdom
Juan Iglesias
Muhammad Bin Idu Jion
Maciej Lesiak
Gioel Gabrio Secco
Thierry Royer
Stéphane Carlier
Stephane Cook
Michal Hawranek
Jean-Louis Mas
Joanna Szachniewicz
Bernhard Meier
Fina Mauri
Sonia Petronio