The sirolimus DEB was noninferior to usual care for TLF at 1 year (16.2% vs 14.5%; difference 1.7%, 95% CrI -5.5% to 8.9%), but not noninferior to DES for single-layer ISR.
RCT (n=418)
randomly assigned
Does a sirolimus drug-eluting balloon reduce target lesion failure compared to usual care (DES or balloon angioplasty) in patients with coronary in-stent restenosis?
A novel sirolimus drug-eluting balloon was noninferior to a usual care strategy (mostly repeat DES) for target lesion failure at 1 year in patients with coronary in-stent restenosis, though it was not noninferior to DES specifically for single-layer ISR.
Effect estimate: Difference 1.7% (95% CI -5.5% to 8.9%)
Absolute Event Rate: 16.2% vs 14.5%
p-value: posterior probability of noninferiority: 98.80%
BACKGROUND: Drug-eluting stents (DESs) are recommended treatment for coronary in-stent restenosis (ISR) but are not used in >20% of cases. OBJECTIVES: The aim of the SELUTION4ISR (SELUTION SLR 014 In-stent Restenosis) trial was to assess the safety and effectiveness of a novel sirolimus drug-eluting balloon (DEB). METHODS: After successful lesion predilation, patients with ISR were randomly assigned to the SELUTION Sustained Limus Release (MedAlliance) DEB or a control strategy of usual care, including any approved DES or balloon angioplasty (BA) on the basis of operator selection prerandomization. Randomization to selected BA control treatment was limited to 20% of patients. The primary outcome was target lesion failure (TLF) (cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization) assessed at 1 year in the per protocol group (all treated eligible patients with complete primary endpoint follow-up). Noninferiority was established if the upper limit of the 2-sided 95% credible interval was smaller than 10%. A sequential secondary hypothesis test was performed comparing DEB with DES in patients with single-layer ISR. RESULTS: From July 2020 to July 2024, 418 patients were randomly assigned to the DEB group (n = 210) or the control group (n = 208), with 390 patients per protocol (DEB, 197; control, 193 154 DES; 39 BA). TLF occurred in 32 (16.2%) of 197 patients in the DEB group and in 28 (14.5%) of 193 patients in the control group (difference: 1.7%; 95% credible interval: -5.5% to 8.9%; posterior probability of noninferiority: 98.80%). In the secondary hypothesis test, TLF occurred in 22 (14.2%) of 155 patients in the DEB group and in 9 (6.5%) of 138 patients in the DES control group (difference: 7.7%; 95% credible interval: 0.6%-14.6%, posterior probability for noninferiority: 76.07%). TLF according to operator selected control was higher for DEB compared with DES (15.3% vs 7.1%; difference: 8.1%; 95% credible interval: 1.4%-15.0%) and lower for DEB compared with BA (23.6% vs 43.6%; difference: 23.7%; 95% credible interval: -41.4% to -1.5%; Pforinteraction = 0.0026). CONCLUSIONS: The sirolimus DEB was noninferior to a usual care control strategy including 80% repeat DES but not noninferior to DES for single-layer ISR for TLF at 12 months. There was significant interaction on the basis of operator selection of DES vs BA. (SELUTION SLR 014 In-stent Restenosis SELUTION4ISR; NCT04280029).
“For the first time, we've shown that a sirolimus-eluting balloon can match the outcomes of standard care for in-stent restenosis while avoiding yet another metal layer. This opens the door to treating restenosis in a simpler, safer way. This study represents an important advance in how we manage restenosis. Patients with multiple stent layers have long faced limited options. A drug-eluting balloon that performs as well as a new stent could be a true paradigm shift.”
Cutlip et al. (2026) conducted an RCT in coronary in-stent restenosis (ISR) (n=418). sirolimus drug-eluting balloon (DEB) vs. usual care (approved DES or balloon angioplasty) was evaluated on target lesion failure (TLF) (cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization) at 1 year (Difference 1.7%, 95% CI -5.5% to 8.9%, p=posterior probability of noninferiority: 98.80%). The sirolimus DEB was noninferior to usual care for TLF at 1 year (16.2% vs 14.5%; difference 1.7%, 95% CrI -5.5% to 8.9%), but not noninferior to DES for single-layer ISR.