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.
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 hypercholesterolemicswine. METHODS AND RESULTS: A total of 44 familial hypercholesterolemicswine 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 hypercholesterolemicswine.
Authors: Tina Binderup; Raphaël Duivenvoorden; Francois Fay; Mandy M T van Leent; Joost Malkus; Samantha Baxter; Seigo Ishino; Yiming Zhao; Brenda Sanchez-Gaytan; Abraham J P Teunissen; Yohana C A Frederico; Jun Tang; Giuseppe Carlucci; Serge Lyashchenko; Claudia Calcagno; Nicolas Karakatsanis; Georgios Soultanidis; Max L Senders; Philip M Robson; Venkatesh Mani; Sarayu Ramachandran; Mark E Lobatto; Barbara A Hutten; Juan F Granada; Thomas Reiner; Filip K Swirski; Matthias Nahrendorf; Andreas Kjaer; Edward A Fisher; Zahi A Fayad; Carlos Pérez-Medina; Willem J M Mulder Journal: Sci Transl Med Date: 2019-08-21 Impact factor: 17.956
Authors: Vijaya B Kolachalama; Stephen D Pacetti; Joseph W Franses; John J Stankus; Hugh Q Zhao; Tarek Shazly; Alexander Nikanorov; Lewis B Schwartz; Abraham R Tzafriri; Elazer R Edelman Journal: Circulation Date: 2013-04-12 Impact factor: 29.690
Authors: Noemi Pavo; Eslam Samaha; Inna Sabdyusheva; Rembert Pogge von Strandmann; Stefanie Stahnke; Christian A Plass; Katrin Zlabinger; Dominika Lukovic; Zoltan Jambrik; Imre J Pavo; Jutta Bergler-Klein; William A Gray; Gerald Maurer; Mariann Gyöngyösi Journal: J Mater Sci Mater Med Date: 2016-07-07 Impact factor: 3.896