1. Vascular Response to Zotarolimus-Coated Balloons in Injured Superficial Femoral Arteries of the Familial Hypercholesterolemic Swine
- Author
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Greg L. Kaluza, Krzysztof Milewski, Alexander Nikanorov, Juan F. Granada, John Stankus, Christian G. Krueger, Renu Virmani, Armando Tellez, Hugh Zhao, Michael S. Aboodi, and Lewis B. Schwartz
- Subjects
medicine.medical_specialty ,Swine ,medicine.medical_treatment ,Urology ,Balloon ,Catheterization ,Hyperlipoproteinemia Type II ,Postoperative Complications ,Clinical Protocols ,Pharmacokinetics ,Restenosis ,Neointima ,Angioplasty ,medicine ,Animals ,Humans ,Zotarolimus ,Sirolimus ,Neointimal hyperplasia ,Vascular disease ,business.industry ,TOR Serine-Threonine Kinases ,Infusion Pumps, Implantable ,medicine.disease ,Surgery ,Peripheral ,Femoral Artery ,Radiography ,Models, Animal ,Cardiology and Cardiovascular Medicine ,business ,Angioplasty, Balloon ,medicine.drug - Abstract
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.
- Published
- 2011