Evaluation of efficacy and dose response of different paclitaxel-coated balloon formulations in a novel swine model of iliofemoral in-stent restenosis.
OBJECTIVE
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 < 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.


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.
Skirball Center for Cardiovascular Research, Cardiovascular Research Foundation, Orangeburg, NY 10962, USA.
Krzysztof
K
Milewski
Maxwell Eyram
ME
Afari
Armando
A
Tellez
Michael S
MS
Aboodi
Jung-Sun
JS
Kim
Yanping
Y
Cheng
Gerard B
GB
Conditt
Jennifer C
JC
McGregor
Geng Hua
GH
Yi
Mark
M
Stenoien
Dan
D
Langanki
Christian G
CG
Krueger
Greg L
GL
Kaluza
Juan F
JF
Granada
D000704:Analysis of Variance; D000800:Angioplasty, Balloon / Q000379:methods*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000627:therapeutic use*; D017023:Coronary Angiography; D023903:Coronary Restenosis / Q000000981:diagnostic imaging / Q000517:prevention & control*; D003331:Coronary Vessels; D004195:Disease Models, Animal; D006305:Health Status Indicators; D006938:Hyperlipoproteinemia Type II / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000628:therapy*; D008297:Male; D017239:Paclitaxel / Q000008:administration & dosage / Q000627:therapeutic use*; D012307:Risk Factors; D014463:Ultrasonography
D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel