Ultrathin-strut drug-eluting stents are associated with lower revascularization rates than drug-coated balloons in non-focal in-stent restenosis.

BACKGROUND: In-stent restenosis (ISR) remains a significant clinical challenge despite advances in drug-eluting stent (DES) technology. Although current guidelines recommend drug-coated balloon (DCB) angioplasty or repeat DES implantation for DES-ISR, real-world data comparing DCB with newer-generation ultrathin-strut sirolimus-eluting stents (SES) are limited. METHODS: This retrospective, single-center study included consecutive patients with stable angina who underwent treatment for DES-ISR using either a paclitaxel-coated DCB or an ultrathin-strut SES between January 2015 and May 2025. The primary outcome was target-lesion revascularization (TLR). Secondary endpoints included major adverse cardiac events (MACE), defined as a composite of all-cause mortality, myocardial infarction, stroke, and TLR. Time-to-event analyses were performed using Kaplan-Meier methods and Cox proportional hazards regression. RESULTS: A total of 205 patients were included (DCB, n = 106; SES, n = 99), with a median follow-up of 863 days. In the overall cohort, TLR rates were comparable between groups. However, in the non-focal ISR subgroup, TLR was significantly higher in the DCB group compared with SES (34.1% vs. 12.7%, p = 0.024). Similarly, MACE rates were higher with DCB in non-focal ISR (39.0% vs. 18.2%, p = 0.041). No differences were observed in focal ISR. Multivariable analysis in the non-focal subgroup identified DCB treatment (HR 3.89, p = 0.006) as independent predictor of TLR. Kaplan-Meier analyses for TLR and MACE consistently demonstrated significantly worse outcomes with DCB in the non-focal ISR subgroup, whereas no significant differences were observed in focal ISR. CONCLUSIONS: Ultrathin-strut SES was associated with lower TLR and MACE rates compared with DCB in non-focal DES-ISR, whereas outcomes were comparable in focal ISR. These findings highlight the importance of lesion characteristics and support a tailored approach to ISR management.