Christian Spaulding, Florian Krackhardt, Kris Bogaerts, Eltigani Abdelaal, Fernándo Alfonso, Carlo Briguori, Leonhard Bruch, Nicholas Cruden, Alexander den Hartog, Philippe Garot, Matthieu Godin, David Hildick‐Smith, Thomas Johnson, Andrew Ladwiniec, Axel Linke, Clint Maart, Kambis Mashayekhi, Pascal Meier, Ludovic MEUNIER, Kenneth Morgan, Peter O’Kane, Étienne Puymirat, Tuomas T. Rissanen, Manel Sabaté, Thomas Schmitz, Gábor G. Tóth, Jasper Trevelyan, Piotr Wanczura, Marcus Wiemer, Joanna J. Wykrzykowska, P Urban, Simon Eccleshall, Mathias Frick, Clemens Steinwender, Leoš Pleva, Martin Poloczek, Guillaume Cayla, N Delarche, Pierre Poustis, Martin Andrassy, Ralf Birkemeyer, Fabian Brunner, F Edelmann, Marcel Halbach, Christoph Langer, Faridun Daniel Rahimi Nedjat, Joachim Schofer, Bastian Wein, Dario Bongiovanni, Maurizio d’Amico, Gioel Gabrio Secco, F Ugo, Dickinson Ml, Madera Cambero, Maciej Lesiak, Kamil Skoczyński, Muhammad Idu, F Ming, Víctor A Jiménez Díaz, D Marrero Arroyo, Jonas Häner, Juan F. Iglesias, Gregor Leibundgut, Johannes Rigger, Barbara Stähli, Freidoon Keshavarzi, Nick Cruden, N Curzen, Karim Ratib, Neil Ruparelia, Andrew Peter Vanezis, Stuart Watkins, Juan Iglesias, Muhammad Idu, Maciej Lesiak, Gioel Gabrio Secco, Thierry Royer, S Carlier, Stéphane Cook, Michał Hawranek, Jean-Louis Mas, Joanna Szachniewicz, B Meier, Fina Mauri, Sonia Petronio
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.