Cardiology · Medical Literature
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
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. 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. 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. 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. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04859985.
Clinical relevance
In patients with de novo coronary artery disease undergoing PCI, is a strategy of sirolimus-eluting balloon (SEB) with provisional DES implantation noninferior to systematic DES implantation for reducing target vessel failure (TVF) at one year? __SNAPSHOT__ {"studyDesign":"Multicenter, open-label, randomized, noninferiority trial (SELUTION DeNovo; NCT04859985)","setting":"62 sites across 12 countries in Europe and Asia; all-comer PCI population","sampleSize":"n=3,341 randomized (SEB arm: n=1,671; DES arm: n=1,670); primary analysis population n=3,323 (patients with completed or attempted revascularization, ITT)","population":"Adults with de novo coronary lesions in vessels 2–5 mm in diameter, presenting with chronic coronary syndrome, unstable angina, or NSTEMI (approximately 32.7% ACS). High proportions of patients with high bleeding risk and acute coronary syndromes were enrolled. Exclusions included STEMI, left main disease, chronic total occlusions, in-stent restenosis, saphenous vein or arterial conduit lesions.","intervention":"SELUTION SLR sirolimus-eluting balloon (SEB), delivering sirolimus via a biodegradable phospholipid polymer micro-reservoir technology over a 90-day elution period, with provisional DES implantation only if required (approximately 20% of SEB-arm patients received a provisional stent; approximately 80% were stent-free)","comparator":"Systematic drug-eluting stent (DES) implantation for all target lesions","primaryOutcome":"Target vessel failure (TVF) at 1 year: a composite of cardiac death, target vessel–related myocardial infarction, and clinically driven target vessel revascularization. Noninferiority margin set at 50% of the combined event rate (absolute margin); significance level 0.025 (one-sided).","followUp":"1 year (primary endpoint); planned follow-up to 5 years with additional noninferiority and superiority testing at 5 years","fundingSource":"Industry (M.A. Med Alliance SA, a Cordis Company, Switzerland)"}
Key findings
The primary endpoint of TVF at 1 year occurred in 5.3% of patients in the SEB arm versus 4.4% in the DES arm. The risk difference was 0.91% (95% CI: −0.55% to 2.38%), and the noninferiority criterion was met (P-noninferiority = 0.02). The absolute risk difference of 0.91% favored DES numerically but fell within the prespecified noninferiority margin. The NNH for TVF at 1 year (calculated as the reciprocal of the absolute risk difference) is approximately 110 (calculated), indicating that for approximately every 110 patients treated with the SEB strategy instead of systematic DES, one additional TVF event would be expected over 1 year. Clinically driven target vessel revascularization occurred in 3.3% (SEB) versus 2.1% (DES); the absolute difference of 1.2% was numerically greater in the SEB arm but specific p-values for this component are not reported in available sources. No acute or late safety signal was identified; secondary safety endpoints were not different between arms. In prespecified unadjusted subgroup analyses, significant interactions were observed: women had a higher TVF rate with SEB than DES (P-interaction = 0.04); patients with high bleeding risk had lower TVF with SEB (P-interaction = 0.04); and patients with moderate-to-severe coronary calcification had lower TVF with SEB (P-interaction = 0.01). The absolute event rates for individual components (cardiac death, target vessel MI) are not reported in currently available sources beyond the conference presentation.
Practice implications
This trial establishes that, at 1 year, an SEB-based strategy with provisional stenting is noninferior to systematic DES implantation for TVF in a broad, all-comer PCI population. Crucially, 80% of patients randomized to the SEB arm avoided permanent metallic stent implantation, achieving the trial's conceptual goal of a 'leave-nothing-behind' strategy. However, what the trial does NOT yet establish is: (1) long-term (≥5-year) noninferiority or superiority—prior experience with bioabsorbable scaffolds cautions against assuming short-term equivalence predicts late outcomes; (2) superiority over DES on any endpoint; (3) applicability to STEMI, left main disease, CTOs, or saphenous vein graft disease, all of which were excluded; and (4) generalizability to patient populations outside Europe and Asia, or to operators less experienced with SEB technique. The numerical disadvantage for SEB (5.3% vs. 4.4% TVF) and higher clinically driven revascularization (3.3% vs. 2.1%) are modest in absolute terms but may have implications for individual patient decisions, particularly in women (who appeared to fare worse with SEB) and those without high bleeding risk or calcification (who did not appear to benefit differentially). The noninferiority margin (50% of combined event rate) is clinically meaningful but on the wider end of accepted practice; some experts have noted this merits consideration when interpreting the result. Industry funding introduces potential for bias and should be weighted in evidence appraisal. Only the abstract and conference presentation data were available at time of summary; the full peer-reviewed publication in Circulation (PMID 42290366, July 2026) was not accessible for detailed review, which limits the ability to assess statistical methods, per-protocol sensitivity analyses, and complete adverse event data. __LIMITATIONS__ Open-label design (neither patients nor operators blinded) introduces performance and assessment bias, particularly for soft endpoints such as clinically driven revascularization.,Industry funding (device manufacturer) with potential for design, reporting, and publication bias.,Noninferiority margin set at 50% of the combined event rate is relatively wide; some investigators have characterized this as permissive, which lowers the evidentiary bar for declaring noninferiority.,Follow-up limited to 1 year; the key mechanistic rationale for the SEB strategy—avoidance of late stent complications (neo-atherosclerosis, very late stent thrombosis, annual 2–4% adverse event rate with DES)—cannot be evaluated at this timeframe.,Significant subgroup interactions (sex, bleeding risk, calcification) were unadjusted and exploratory; they are hypothesis-generating only and must not be used for treatment selection without confirmatory data.,STEMI, left main, CTO, vein grafts, and ISR were excluded, limiting generalizability to these common high-risk subsets.,Geographic restriction to Europe and Asia limits applicability to North American and other global practice settings.,Higher provisional stent rate (approximately 20% of SEB patients) than some previous DCB trials; 'stent-free' outcome applies to approximately 80%, not all, of the SEB arm.,Complete component-level adverse event data (cardiac death rates, MI rates by arm) are not fully reported in available pre-publication sources.,Full peer-reviewed manuscript not available for independent methodological appraisal at the time of this summary. __BOTTOM_LINE_CATEGORY__ potentially_practice_informing __BOTTOM_LINE__ The SELUTION DeNovo trial demonstrates that a sirolimus-eluting balloon strategy with provisional stenting is noninferior to systematic DES implantation for TVF at 1 year in an all-comer PCI population, with 80% of SEB-arm patients avoiding a permanent stent and no observed safety concerns at 1 year. However, the numerical TVF disadvantage for SEB, industry sponsorship, an open-label design, a relatively wide noninferiority margin, and the absence of long-term data (particularly beyond 1 year, when the 'leave-nothing-behind' benefit is theorized to accrue) argue against immediate wholesale practice change. Clinicians may reasonably consider this strategy in selected patients—particularly those at high bleeding risk or with significant calcification—while awaiting 5-year outcome data and independent replication.