TY - JOUR
T1 - Vascular response to zotarolimus-coated balloons in injured superficial femoral arteries of the familial hypercholesterolemic swine
AU - Granada, Juan F.
AU - Milewski, Krzysztof
AU - Zhao, Hugh
AU - Stankus, John J.
AU - Tellez, Armando
AU - Aboodi, Michael S.
AU - Kaluza, Greg L.
AU - Krueger, Christian G.
AU - Virmani, Renu
AU - Schwartz, Lewis B.
AU - Nikanorov, Alexander
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2011/10
Y1 - 2011/10
N2 - Background-Drug-coated balloons are rapidly emerging as a therapeutic alternative for the interventional treatment of peripheral vascular disease. The purpose of this study was to test the hypothesis that an angioplasty balloon coated with the mTOR inhibitor zotarolimus (ZCB) would inhibit neointimal hyperplasia in a novel injury-based superficial femoral artery model in the familial hypercholesterolemic swine. Methods and Results-A total of 44 familial hypercholesterolemic swine were included (12 designated to study tissue pharmacokinetics and 32 to study safety and efficacy). Fogarty balloon denudation was performed in all superficial femoral artery segments, followed by balloon angioplasty. In the pharmacokinetic study, a total of 24 ZCBs (300 μg/cm 2) were used. Zotarolimus was detected in arterial tissue at 5 minutes (162 ng/mg of tissue), 24 hours (5.9 ng/mg of tissue), and 28 days (0.007 ng/mg of tissue) after ZCB inflation. In the safety and efficacy study, superficial femoral artery segments were randomized to either high-dose (600 μg/cm 2, n=16), low-dose (300 μg/cm 2, n=16), or paired uncoated balloons (high-dose ZCB control, n=16; low-dose ZCB control, n=16). At 28 days, the percentage of angiographic stenosis was similar among all tested groups. Histological analysis demonstrated a reduction in neointimal formation in both ZCB groups compared with controls (high-dose ZCB 44% reduction, P=0.007; low-dose ZCB 22% reduction, P=0.08). There was no evidence of delayed arterial healing or vascular toxicity in any of the ZCB groups. Conclusions-The single delivery of zotarolimus via coated balloon is feasible, and therapeutic levels are maintained up to 28 days. The ZCB technology appears to be effective in the reduction of neointimal proliferation in the superficial femoral artery of the familial hypercholesterolemic swine.
AB - Background-Drug-coated balloons are rapidly emerging as a therapeutic alternative for the interventional treatment of peripheral vascular disease. The purpose of this study was to test the hypothesis that an angioplasty balloon coated with the mTOR inhibitor zotarolimus (ZCB) would inhibit neointimal hyperplasia in a novel injury-based superficial femoral artery model in the familial hypercholesterolemic swine. Methods and Results-A total of 44 familial hypercholesterolemic swine were included (12 designated to study tissue pharmacokinetics and 32 to study safety and efficacy). Fogarty balloon denudation was performed in all superficial femoral artery segments, followed by balloon angioplasty. In the pharmacokinetic study, a total of 24 ZCBs (300 μg/cm 2) were used. Zotarolimus was detected in arterial tissue at 5 minutes (162 ng/mg of tissue), 24 hours (5.9 ng/mg of tissue), and 28 days (0.007 ng/mg of tissue) after ZCB inflation. In the safety and efficacy study, superficial femoral artery segments were randomized to either high-dose (600 μg/cm 2, n=16), low-dose (300 μg/cm 2, n=16), or paired uncoated balloons (high-dose ZCB control, n=16; low-dose ZCB control, n=16). At 28 days, the percentage of angiographic stenosis was similar among all tested groups. Histological analysis demonstrated a reduction in neointimal formation in both ZCB groups compared with controls (high-dose ZCB 44% reduction, P=0.007; low-dose ZCB 22% reduction, P=0.08). There was no evidence of delayed arterial healing or vascular toxicity in any of the ZCB groups. Conclusions-The single delivery of zotarolimus via coated balloon is feasible, and therapeutic levels are maintained up to 28 days. The ZCB technology appears to be effective in the reduction of neointimal proliferation in the superficial femoral artery of the familial hypercholesterolemic swine.
KW - Angioplasty balloon
KW - Hypercholesterolemic swine
KW - Peripheral vascular disease
KW - Restenosis
KW - Zotarolimus
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U2 - 10.1161/CIRCINTERVENTIONS.110.960260
DO - 10.1161/CIRCINTERVENTIONS.110.960260
M3 - Article
C2 - 21953371
AN - SCOPUS:82955229559
SN - 1941-7640
VL - 4
SP - 447
EP - 455
JO - Circulation: Cardiovascular Interventions
JF - Circulation: Cardiovascular Interventions
IS - 5
ER -