Evaluation of Efficacy and Dose Response of Different Paclitaxel-Coated Balloon Formulations in a Novel Swine Model of Iliofemoral In-Stent Restenosis

Objectives The authors aimed to validate a novel iliofemoral in-stent restenosis (ISR) model for the efficacy evaluation of paclitaxel-coated balloons (PCB) using the familial hypercholesterolemic swine (FHS). Background Most of the validation work regarding PCB technologies has been performed in the coronary territory of juvenile domestic swine. Although invaluable for safety evaluation, this model is not suited for the evaluation of the efficacy of peripheral PCB technologies. Methods Twenty-four iliofemoral segments in 12 FHS underwent balloon injury and self-expanding stent placement. After 21 days, the resulting ISR lesions were treated with either 1 μg/mm 2 dose (n = 8), or 3 μg/mm 2 dose (n = 8) PCB (Cotavance, Bayer Pharma AG/MEDRAD, Indianola, Pennsylvania), or with an identical uncoated control balloon (n = 8). Results At termination (28 days after treatment), the percent diameter stenosis by quantitative vascular analysis in the control group was higher (31.2 ± 13.7%) compared with the 1 μg/mm 2 (19.3 ± 14.0%, 38% reduction) and 3 μg/mm 2 (8.6 ± 10.7%, 72% reduction) PCB groups. Intravascular ultrasound analysis showed 36% (1 μg/mm 2 dose, p = 0.04) and 55% (3 μg/mm 2 dose, p 2 and 3 μg/mm 2 dose groups, respectively. Conclusions The FHS model of iliofemoral ISR demonstrated a dose-dependent effect on the inhibition of neointimal proliferation of a clinically validated PCB technology. This model represents a positive step toward the efficacy evaluation of PCB in the peripheral vascular territory.