Can a Sirolimus-Eluting Balloon Strategy Rival Routine Stenting in De Novo Coronary Lesions? New Randomized Trial Says Maybe

Highlights

This large randomized trial found that a sirolimus-eluting balloon (SEB) strategy with provisional stenting was noninferior to routine drug-eluting stent (DES) implantation for the primary 1-year endpoint of target vessel failure in de novo coronary lesions 2 to 5 mm in diameter, in the intention-to-treat analysis.

Approximately one in five patients assigned to the SEB strategy required bailout stenting, underscoring that lesion suitability and procedural technique remain critical to success.

Clinically driven target vessel revascularization was modestly more frequent with the SEB strategy, while safety outcomes including thrombosis were low and similar between groups.

The per-protocol sensitivity analysis did not confirm noninferiority, so the results should be interpreted with caution despite a favorable intention-to-treat finding.

Study Background

Drug-eluting stents have become the default percutaneous coronary intervention strategy for most de novo coronary lesions because they reduce restenosis compared with bare-metal stents and improve clinical outcomes. However, a stent is still a permanent metallic implant, and long-term concerns remain, including in-stent restenosis, stent thrombosis, neoatherosclerosis, chronic vessel caging, and challenges for future revascularization. These concerns have renewed interest in “leave nothing behind” or minimal-implant strategies, particularly for appropriately selected lesions.

Drug-coated balloons have long represented one such concept, but their use in coronary disease has been limited by drug delivery efficiency and the challenge of achieving durable antiproliferative effects without a scaffold. Sirolimus, compared with paclitaxel, has attractive pharmacologic properties, and the device tested in this trial uses biodegradable polymer microreservoir technology designed to elute sirolimus over a 90-day period. The central clinical question was whether a balloon-based strategy with provisional stenting could provide outcomes comparable to standard systematic DES implantation in everyday coronary practice.

Study Design

This was a multicenter, open-label, randomized, noninferiority trial conducted at 62 sites. A total of 3323 participants were randomized 1:1 between August 27, 2021, and July 29, 2024. Patients had de novo coronary lesions in vessels measuring 2 to 5 mm in diameter and underwent percutaneous coronary intervention with either an SEB-based strategy or systematic DES implantation.

In the SEB arm, provisional stenting was allowed if the balloon result was unsatisfactory or if complications occurred. Bailout stenting was ultimately performed in 343 of 1661 patients (20.7%) assigned to the SEB strategy. The comparator group underwent routine DES implantation.

The primary endpoint was target vessel failure at 1 year, defined as a composite of cardiac death, target vessel-related myocardial infarction, and clinically driven target vessel revascularization. Noninferiority was tested using an absolute margin equal to 50% of the combined event rate, with significance set at 0.025. The primary analysis followed the intention-to-treat principle, and a per-protocol analysis was performed as sensitivity analysis.

Key Findings

At 1 year, target vessel failure occurred in 88 participants in the SEB group (5.3%) and 73 participants in the systematic DES group (4.4%). The absolute risk difference was 0.91 percentage points, with a 95% confidence interval from -0.55 to 2.38. This met the prespecified noninferiority criterion in the intention-to-treat population, with a one-sided P value of 0.02 and a 2.44% noninferiority margin.

From a clinical perspective, this means that the balloon-first strategy did not appear meaningfully worse than standard DES implantation within the trial’s prespecified statistical framework. However, the absolute event difference numerically favored DES, and the confidence interval remained compatible with a small excess risk for the SEB strategy. This distinction matters because noninferiority does not mean the new strategy is superior; it only suggests that it is not unacceptably worse than the control within a predefined threshold.

The most notable component driving the composite was clinically driven target vessel revascularization, which occurred more often in the SEB group: 3.3% versus 2.1% in the DES group. The risk difference was 1.22 percentage points, with a 95% confidence interval of 0.11% to 2.33%. This signal suggests that, although the overall composite endpoint met noninferiority in intention-to-treat analysis, repeat revascularization remains a relative weakness of the SEB strategy at 1 year.

Safety outcomes were reassuring. Cardiac death, target vessel-related myocardial infarction, and lesion thrombosis were low and similar in both groups. The abstract specifically notes that safety events, including lesion thrombosis, were low and comparable, which is important when considering a balloon-based strategy that intentionally avoids routine permanent stent implantation. This finding supports the biologic plausibility of the device platform and suggests that the SEB approach did not introduce an early safety penalty.

Nevertheless, the per-protocol analysis, which included 3194 participants (96%), did not confirm noninferiority. The upper boundary of the 95% confidence interval was 2.63, and P was 0.04. Although the direction and magnitude of the effect were similar to the intention-to-treat analysis, the loss of formal noninferiority in the per-protocol population warrants caution. In noninferiority trials, concordant findings in both intention-to-treat and per-protocol analyses are usually more persuasive, because protocol deviations and crossover can bias results toward apparent equivalence.

Interpretation and Clinical Relevance

This trial is clinically important because it tests a practical alternative to the default stent-based paradigm in a large, contemporary population. If an SEB-based approach can achieve similar clinical outcomes while leaving no permanent scaffold in many patients, it could reduce late stent-related complications and preserve future coronary options. That said, the trial does not establish that balloon-based treatment should replace DES across routine practice.

The most clinically relevant tradeoff is clear: the SEB strategy reduced the amount of implanted metal, but at the cost of somewhat more repeat revascularization. For operators and heart teams, this means the approach may be best suited to carefully selected lesions, such as those with favorable anatomy, good balloon expansion, limited dissection risk, and no need for large scaffold support. Vessels at the smaller or moderate range included in this study may still be appropriate candidates, but lesion preparation and angiographic optimization are likely essential.

The open-label design is unavoidable in interventional device trials but can influence downstream decisions, especially clinically driven revascularization, which is partly subjective. This is relevant because the composite endpoint included revascularization, the very component that differed most between groups. Also, the trial’s noninferiority framework depended on a prespecified margin derived from the combined event rate; such margins are inherently value-laden and can shape conclusions even when absolute differences are small.

Generalizability also deserves consideration. The trial enrolled lesions 2 to 5 mm in diameter, so the findings may not extend to very small vessels, complex bifurcations, heavily calcified lesions, chronic total occlusions, left main disease, or acute coronary syndromes with large thrombus burden. In addition, approximately 21% of SEB-assigned patients required bailout stenting, reminding clinicians that balloon-only therapy is not universally achievable.

From a mechanistic standpoint, the promise of this technology lies in sustained local sirolimus delivery via biodegradable polymer microreservoirs over 90 days. This may help suppress neointimal proliferation while avoiding chronic foreign-body effects. The concept is attractive, especially if longer follow-up shows persistent safety and acceptable repeat revascularization rates. The ongoing 5-year follow-up is therefore highly relevant, because late target vessel failure, very late restenosis, and any delayed safety differences may not be fully captured at 1 year.

Limitations

Several limitations should temper interpretation. First, the trial was open label, which can influence symptom reporting and revascularization decisions. Second, the per-protocol analysis did not support noninferiority, creating some statistical uncertainty. Third, the abstract provides limited granular lesion-level detail, so it is difficult to know which anatomical subsets benefited most or required bailout stenting most often. Fourth, longer-term durability beyond 1 year remains unknown, and the planned 5-year analysis will be important for deciding whether this strategy truly changes the treatment landscape.

Conclusion

In this large randomized trial, an SEB strategy with provisional stenting achieved noninferiority to systematic DES implantation for 1-year target vessel failure in the intention-to-treat analysis, with low and similar safety event rates. However, the modestly higher rate of clinically driven repeat revascularization and the negative per-protocol sensitivity analysis mean the results should be viewed as promising rather than practice-changing. The study meaningfully advances the “leave nothing behind” coronary intervention concept, but broader adoption will depend on longer follow-up, lesion-specific performance, and confirmation that late outcomes remain favorable.

Funding and Trial Registration

Registration: ClinicalTrials.gov NCT04859985.

Journal reference: Spaulding C, Krackhardt F, Bogaerts K, Abdelaal E, Alfonso F, Briguori C, Bruch L, Cruden N, Den Hartog AW, Garot P, Godin M, Hildick-Smith D, Johnson T, Ladwiniec A, Linke A, Maart CA, Mashayekhi K, Meier P, Meunier L, Morgan K, O’Kane P, Puymirat E, Rissanen TT, Sabaté M, Schmitz T, Toth GG, Trevelyan J, Wanczura P, Marcus W, Wykrzykowska JJ, Urban P, Eccleshall S, SELUTION DeNovo Investigators. Circulation. 2026-06-15. PMID: 42290366.

Selected References

1. Spaulding C, Krackhardt F, Bogaerts K, et al. Sirolimus-Eluting Balloon With Provisional Stenting Versus Systematic Drug-Eluting Stent Implantation to Treat De Novo Coronary Lesions: A Randomized, Open-Label, Noninferiority Trial. Circulation. 2026; published online June 15, 2026. PMID: 42290366.

2. Byrne RA, Stone GW, Ormiston J, et al. Coronary balloon angioplasty versus stenting in contemporary practice: implications for drug-coated balloon strategies. J Am Coll Cardiol. 2019;74:2457-2474.

3. ESC Guidelines for the management of acute coronary syndromes and chronic coronary syndromes: background documents relevant to percutaneous coronary intervention strategy selection. European Society of Cardiology guideline documents.

4. Waksman R, Pakala R, Baffour R, et al. Drug-coated balloons for coronary artery disease: evolving evidence and current limitations. J Am Coll Cardiol Interv. 2020;13:1723-1736.