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

• DOI: 10.1016/j.jcin.2012.06.012
• Publication Date: 2012-10-15T23:31:25Z
• Authors: Krzysztof Milewski; Maxwell Eyram Afari; Armando Tellez; Michael S. Aboodi; Jung-Sun Kim; Yanping Cheng; Gerard B. Conditt; Jennifer C. McGregor; Geng Hua Yi; Mark Stenoien; Dan Langanki; Christian G. Krueger; Greg L. Kaluza; Juan F. Granada
• Keywords: Male; familial hypercholesterolemic swine; Analysis of Variance; Paclitaxel; paclitaxel-coated balloon; in-stent restenosis; Coronary Angiography; Antineoplastic Agents, Phytogenic; Coronary Vessels; 3. Good health; Coronary Restenosis; Hyperlipoproteinemia Type II; Disease Models, Animal; 03 medical and health sciences; 0302 clinical medicine; Risk Factors; iliofemoral arteries; Animals; Health Status Indicators; Cardiology and Cardiovascular Medicine; Angioplasty, Balloon; Ultrasonography

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).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.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).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 < 0.01) reductions in neointimal volume stenosis. In the histological analysis, the control group showed the highest degree of percent area stenosis (65 ± 14.3%). The reductions in percent area stenosis was 13.2% (p = 0.5) and 26% (p = 0.04) in the 1 μg/mm(2) and 3 μg/mm(2) dose groups, respectively.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.