Prepared by: Dr. Ülkü Nur Koç, Dr. Yücel Kanal

Study Title: Head-to-head comparison of Limus vs Paclitaxel DCBs in the Treatment of In-Stent Restenosis

Presented at: EuroPCR 2025

Link: https://media.pcronline.com/diapos/EuroPCR2025.pdf
Introduction
In the treatment of drug-eluting stent in-stent restenosis (DES-ISR), drug-coated balloons (DCBs) are increasingly preferred as they can suppress neointimal proliferation without adding additional metal layers to the existing stent structure. Although paclitaxel-coated balloons (PCBs), which arrest the cell cycle in the mitotic phase, have been the most widely used option to date, balloons coated with "Limus"-based agents (LCBs) such as sirolimus or everolimus—operating via an immunosuppressive mechanism—have recently entered clinical practice. While Limus agents are cytostatic, have slow tissue absorption, short tissue retention, and a wide therapeutic window, paclitaxel is cytotoxic, has a narrow therapeutic window, fast tissue absorption, and prolonged tissue retention.

Objective
Due to the limited number of direct comparative studies between these two technologies, Marios Sagris and colleagues conducted a systematic meta-analysis to compare both efficacy and safety.

Methods
Researchers screened data published up to February 15, 2025, including patients with stable/unstable angina or positive functional testing who underwent DCB treatment for DES-ISR. Clinical outcomes, angiographic data, and perioperative complications were evaluated. Five randomized controlled trials and one retrospective cohort were included. Among the 1,208 patients, 569 were treated with PCB and 639 with LCB; the mean follow-up period was 12 months. Primary endpoints were target lesion revascularization (TLR) and target lesion failure (TLF). Secondary endpoints included procedural success, all-cause mortality, MACE (including cardiac death and target vessel MI [TVMI]), and perioperative complications. In advanced analyses, angiographic parameters such as late lumen loss (LLL), minimal lumen diameter (MLD), and diameter stenosis (DS) were also assessed. Study quality was evaluated using the Cochrane RoB-2 tool, and the risk of bias was assessed using the ROBINS-I tool.

Results
There was no clinically significant difference between the two technologies: both TLR and TLF rates were approximately 14% in both groups. Mortality, MACE, and perioperative complication rates were also similar across groups. Angiographic findings revealed a comparable profile: in-segment LLL was reported as 0.40 ± 0.54 mm for PCB and 0.28 ± 0.43 mm for LCB; in-lesion LLL was 0.29 ± 0.43 mm and 0.27 ± 0.48 mm, respectively—none reaching statistical significance. Although binary restenosis rates were 19.5% in the PCB group versus 12.9% in the LCB group, high heterogeneity precluded drawing a definitive conclusion of superiority. Other parameters such as MLD, DS, and reference vessel diameter also showed small differences, with confidence intervals crossing significance thresholds.

Conclusion
Limus-coated balloons have been shown to be as safe and effective as paclitaxel-coated balloons; while a slight trend in favor of PCB in terms of luminal outcomes may be observed, current evidence is insufficient to declare definitive superiority. LCBs demonstrated similar angiographic results to PCBs during the 1-year follow-up, with no significant differences in late lumen loss.

Comments
In routine clinical practice, LCBs may be considered a viable alternative to PCBs in complex ISR cases or long lesions. More informative data may be obtained through extended follow-up to monitor restenosis rates. Further large-scale, long-term randomized trials are still warranted.