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

Local drug delivery is rapidly emerging as the first line of therapy for the interventional treatment of superficial femoral artery (SFA) disease. Paclitaxel-coated balloon (PCB) technologies have shown to be superior to plain balloon angioplasty in maintaining long-term vessel patency among patients undergoing SFA intervention. The pharmacokinetic behavior of PCB is highly variable and largely depends on the size and solubility of the paclitaxel particles delivered to the vessel surface. It has been hypothesized that the variability in paclitaxel tissue levels displayed by PCB technologies may impact the durability of long-term clinical results. In addition, a polymer-free paclitaxel-eluting stent (PES) technology has demonstrated to improve 5-year vessel SFA patency compared with an identical bare metal stent (BMS) control. Similarly, despite the encouraging 12-month patency results, a progressive loss of lumen patency has also been reported and attributed to the highly variable pharmacokinetic profile resulting from the absence of a controlled mechanism of drug release. New-generation peripheral polymer-based drugeluting stents promise to improve vessel patency and healing profile by providing a more sustainable and controllable environment after implantation. In this study, we compared the impact on neointimal proliferation and vascular healing of 2 clinically available peripheral PESs (polymer-free versus fluoropolymer-based) versus a BMS control in the familial hypercholesterolemic model of femoral restenosis. Background—A polymer-free peripheral paclitaxel-eluting stent (PES, Zilver PTX, Cook, IN) has shown to improve vessel patency after superficial femoral angioplasty. A new-generation fluoropolymer-based PES (FP-PES; Eluvia, Boston Scientific, MA) displaying more controlled and sustained paclitaxel delivery promise to improve the clinical outcomes of first-generation PES. We sought to compare the biological effect of paclitaxel delivered by 2 different stent-coating technologies (fluoropolymer-based versus polymer-free) on neointimal proliferation and healing response in the familial hypercholesterolemic swine model of femoral restenosis. Methods and Results—The biological efficacy of clinically available FP-PES (n=12) and PES (n=12) was compared against a bare metal stent control (n=12; Innova, Boston Scientific, MA) after implantation in the femoral arteries of 18 familial hypercholesterolemic swine. Longitudinal quantitative vascular angiography and optical coherence tomography were performed at baseline and at 30 and 90 days. Histological evaluation was performed at 90 days. Ninety-day quantitative vascular angiography results showed a lower percent diameter stenosis for FP-PES (38.78% [31.27–47.66]) compared with PES (54.16% [42.60–61.97]) and bare metal stent (74.52% [47.23–100.00]; P<0.001). Ninety-day optical coherence tomography results demonstrated significantly lower neointimal area in FP-PES (8.01 mm [7.65–9.21]) compared with PES (10.95 mm [9.64–12.46]) and bare metal stent (13.83 mm [11.53–17.03]; P<0.001). Histological evaluation showed larger lumen areas and evidence of higher biological activity (smooth muscle cell loss and fibrin deposition) in the FPPES compared with PES and bare metal stent. Conclusions—In the familial hypercholesterolemic swine model of femoral restenosis, the implantation of an FP-PES resulted in lower levels of neointimal proliferation and sustained biological effect ≤90 days compared with a polymerfree stent-based approach. (Circ Cardiovasc Interv. 2017;10:e004450. DOI: 10.1161/CIRCINTERVENTIONS. 116.004450.)