Test Novel Drug-Coated Balloon Compares Favorably to DES in De Novo Disease and ISR

By Jeffrey Zimmet, MD, PhD

Synopsis: In two related largest-to-date clinical trials, a sirolimus-eluting balloon was noninferior to current-generation drug-eluting stents (DES) in both de novo lesions and in-stent restenosis (ISR).

Source: Spaulding C, on behalf of the SELUTION DeNovo investigators. One-year results of the SELUTION DeNovo trial comparing a strategy of PCI with a sirolimus-eluting balloon and provisional stenting versus systematic DES implantation to treat de novo coronary lesions. Presented at Trans Catheter Therapeutics 2025. Oct. 26, 2025, San Francisco, CA.

Implantation of drug-eluting stents (DES) has been the cornerstone of percutaneous coronary intervention (PCI) for more than two decades. The motivation behind the SELUTION trials arises from persistent concerns surrounding DES, despite their proven track record. Annual rates of very late adverse events (such as stent thrombosis and in-stent restenosis [ISR], estimated between 2% and 4%) remain significant, particularly when additional stents are deployed in previously treated vessels. Drug-coated balloon (DCB) therapy offers the potential for effective drug delivery without additional metal implantation, thus reducing long-term complications and preserving treatment flexibility for future interventions.

A majority of DCB devices to date have used paclitaxel, as is true for the only currently U.S. Food and Drug Administration (FDA)-approved coronary DCB (Agent) in the United States. The SELUTION SLR employs sirolimus — already well-validated in DES — delivered through a proprietary micro-reservoir system designed for controlled drug release over 90 days. The trials were conceived to evaluate whether a stent minimization strategy using the SELUTION DCB could achieve outcomes comparable to systematic DES placement, while maintaining safety and efficacy in both de novo and previously stented (ISR) lesions.

In SELUTION DeNovo, the largest randomized DCB trial to date, 3,323 patients were enrolled across 62 global centers. Participants, encompassing all-comer PCI candidates, were randomized to either SELUTION SLR DCB with provisional stenting or to systematic DES. Importantly, approximately 20% of cases required implantation of stents because of dissection or suboptimal balloon dilatation results. The primary 12-month endpoint was target vessel failure (TVF), defined as a composite of cardiac death, target vessel myocardial infarction (MI), and clinically driven revascularization.

At 12 months, TVF occurred in 5.3% of patients in the DCB arm compared with 4.4% in the DES arm, a risk difference of 0.91% (95% confidence interval [CI], -0.55% to 2.38%; P for noninferiority = 0.02). Rates of cardiac death (0.7% for DCB vs. 1.0% for DES), lesion thrombosis (0.1% vs. 0.3%), and target vessel MI (2.7% vs. 2.6%) were comparably low between groups, and no acute or late safety concerns were observed with the DCB approach. The trial included a significant proportion of complex and high-risk lesions.

The SELUTION4ISR trial enrolled 418 patients with ISR, including those with up to two layers of prior stenting. Participants were randomized to receive the SELUTION SLR DCB or standard of care (80% DES, 20% balloon angioplasty). The primary endpoint was target lesion failure (TLF) at one year. At 12 months, TLF was observed in 15.2% of the DCB group vs. 13.5% of controls, a difference of 1.8% (95% CI, -4.9% to 8.5%), with a posterior probability for noninferiority of 99.18%. Cardiac death, target vessel MI, and clinically driven revascularization rates were statistically comparable, with no additional safety issues identified. The study included a substantial representation of older, diabetic, and complex ISR patients. Dr. Roxana Mehran emphasized the value of having a sirolimus-based DCB that avoids the challenges and complications of multiple metal layers in ISR management.

Investigators from both trials concluded that SELUTION SLR DCB is noninferior to DES for both de novo and ISR cases, achieving positive primary safety and efficacy endpoints in broad, real-world populations. They emphasized the strategy’s ability to minimize stent implantation while preserving future vessel options and potentially mitigating long-term complications inherent to permanent implants. Long-term follow-up data extending to five years currently are being collected to confirm durability, but short-term results already support broader clinical use of DCBs.

Commentary

For many years, most PCI procedures have not been complete until a DES has been implanted in the coronary artery. Clinical trials to date looking at DCB-only approaches to coronary angioplasty have been limited in scope. The implications of the current findings, therefore, are substantial.

SELUTION DCB provides a viable, stent-sparing PCI alternative with outcomes comparable to conventional DES, even in complex lesion subsets and ISR. For U.S. cardiologists, robust multicenter data demonstrating noninferiority support a more individualized approach to patient management, particularly in cases where stent implantation poses technical or clinical challenges. The growing ability to achieve durable outcomes without permanent metal scaffolds directly addresses longstanding concerns around late thrombosis, restenosis, and reintervention. It is important to recognize that multiple very different DCBs are in use worldwide, and these results may very well not translate to paclitaxel-based DCBs, which have produced variable outcomes to date.

If incorporated into guidelines pending FDA review and approval, these results have the potential to alter PCI practice toward a leave-nothing-behind philosophy for appropriate de novo lesions, reserving stents for bailout use when DCB results are suboptimal. In ISR management, this trial used mainly DES as a comparator (as opposed to the AGENT IDE trial, which compared the Agent DCB with plain balloon angioplasty for ISR) and therefore provides more actionable results. Given the inclusion of diverse, high-risk populations, the results appear broadly applicable and relevant for immediate use in U.S. clinical settings. Continued follow-up will be crucial to assess long-term performance, but the current evidence already supports early adoption and wider integration of DCBs into coronary interventions.

In summary, these results give credence to the growing enthusiasm for a scaffold-free approach to coronary revascularization. U.S. cardiologists should closely follow upcoming regulatory reviews and anticipate updates to practice guidelines as the movement toward stent minimization gains strong empirical and clinical support.

Jeffrey Zimmet, MD, PhD, is Associate Professor of Medicine, University of California, San Francisco; Director, Cardiac Catheterization Laboratory, San Francisco VA Medical Center.