Biological effect on drug distribution and vascular healing via paclitaxel‐coated balloon technology in drug eluting stent restenosis swine model

Abstract

ObjectivesTo evaluate the biological effect of a paclitaxel‐coated balloon (PCB) technology on vascular drug distribution and healing in drug eluting stent restenosis (DES‐ISR) swine model.BackgroundThe mechanism of action and healing response via PCB technology in DES‐ISR is not completely understood.MethodsA total of 27 bare metal stents were implanted in coronary arteries and 30 days later the in‐stent restenosis was treated with PCB. Treated segments were harvested at 1 hr, 14 days and 30 days post treatment for the pharmacokinetic analysis. In addition, 24 DES were implanted in coronary arteries for 30 days, then all DES‐ISRs were treated with either PCB (n = 12) or uncoated balloon (n = 12). At day 60, vessels were harvested for histology following angiography and optical coherence tomography (OCT).ResultsThe paclitaxel level in neointimal tissue was about 18 times higher (P = 0.0004) at 1 hr C max, and retained about five times higher (P = 0.008) at day 60 than that in vessel wall. A homogenous distribution of paclitaxel in ISR was demonstrated by using fluorescently labeled paclitaxel. Notably, in DES‐ISR, both termination OCT and quantitative coronary angioplasty showed a significant neointimal reduction and less late lumen loss (P = 0.05 and P = 0.03, respectively) post PCB versus post uncoated balloon. The PES‐ISR + PCB group displayed higher levels of peri‐strut inflammation and fibrin scores compared to the ‐limus DES‐ISR + PCB group.ConclusionsIn ISR, paclitaxel is primarily deposited in neointimal tissue and effectively retained over time following PCB use. Despite the presence of metallic struts, a uniform distribution was characterized. PCB demonstrated an equivalent biological effect in DES‐ISR without significantly increasing inflammation. © 2015 Wiley Periodicals, Inc.

Optical Coherence Tomography Assessment of Glucose Fluctuation Impact on the Neointimal Proliferation After Stent Implantation in a Diabetic/Hypercholesterolemic Swine Model

“…OCT is emerging as a very important imaging device for the evaluation of coronary plaque characteristics and neointimal proliferation after stenting due to its high-resolution. Recent animal and human data 18,19) validated this tool in the evaluation of peri-strut neointimal formation and coverage. In addition, recent studies suggest that the different characteristics of neointimal tissue seen by OCT may correlate with clinical events such as late stent thrombosis.…”

Serial Observations of In-Stent Restenosis Treated With Drug-Coated Balloon Angioplasty by Optical Coherence Tomography and Coronary Angioscopy

“…Previous studies reported OCT-documented late vessel healing and enlargement after DCB angioplasty. 5,6) In animal models, paclitaxel-eluting stent exhibited greater neointimal area and medial necrosis, due to a reduction in endothelial and smooth muscle cells, at follow-up. 7) Similar mechanisms may underlie late vessel healing and enlargement after DCB angioplasty in human coronary arteries.…”

Impact of Fluoropolymer-Based Paclitaxel Delivery on Neointimal Proliferation and Vascular Healing

“…Typically, arterial levels of paclitaxel rapidly decline 72 hours after balloon delivery and fall below therapeutic levels by 180 days. 20 First in-human clinical studies using different PCB technologies demonstrate that PCB decreases angiographic restenosis by 40% to 50% by 6 months after initial delivery compared with PTA. 21,22 However, randomized controlled studies suggest that the effect on restenosis and vessel patency declines after the first 12 months.…”