BACKGROUND: Drug-coated balloons (DCB) are emerging as an alternative to permanent implants for managing de novo coronary artery disease, particularly in small vessels (SVD). This sub-analysis of the PICCOLETO II study aimed to compare the performance of DCB and DES in terms of Murray's law-based quantitative flow ratio (μFR) changes between baseline, post-percutaneous coronary intervention (PCI), and follow-up. METHODS: Patients with a clinical indication for PCI were assigned to receive either Xience DES or Elutax SV/Emperor DCB. Coronary angiograms were blindly analyzed by an independent Core Laboratory (Consorzio Futuro in Ricerca, University of Ferrara, Italy). RESULTS: Among 232 patients, 59 were included in this analysis. Pre-PCI μFR was comparable between groups (0.65 ± 0.29 vs. 0.58 ± 0.25
p = 0.20). Post-PCI, the DCB group had a lower acute functional gain compared to DES (+0.21 vs. +0.31
p = 0.064), with lower μFR values (0.86 ± 0.36 vs. 0.89 ± 0.3
p = 0.074). At 6-month follow-up, μFR values were similar between groups (0.84 ± 0.29 vs. 0.84 ± 0.31, p = 0.93), with a comparable late functional loss (-0.02 vs. -0.05
p = 0.93). Angiographic late lumen loss was significantly lower in the DCB group (-0.03 vs. +0.29 mm
p = 0.027). CONCLUSIONS: DCB-based PCI showed a trend toward less favorable immediate post-PCI functional result but a comparable performance at follow-up, suggesting its potential in treating de novo SVD.