Abstract

Drug-eluting stents (DES), which release anti-proliferative drugs into the arterial wall in a controlled manner, have drastically reduced the rate of in-stent restenosis and revolutionized the treatment of atherosclerosis. However, late stent thrombosis remains a safety concern in DES, mainly due to delayed healing of the endothelial wound inflicted during DES implantation. We present a framework to optimize DES design such that restenosis is inhibited without affecting the endothelial healing process. To this end, we have developed a computational model of fluid flow and drug transport in stented arteries and have used this model to establish a metric for quantifying DES performance. The model takes into account the multi-layered structure of the arterial wall and incorporates a reversible binding model to describe drug interaction with the cells of the arterial wall. The model is coupled to a novel optimization algorithm that allows identification of optimal DES designs. We show that optimizing the period of drug release from DES and the initial drug concentration within the coating has a drastic effect on DES performance. Paclitaxel-eluting stents perform optimally by releasing their drug either very rapidly (within a few hours) or very slowly (over periods of several months up to one year) at concentrations considerably lower than current DES. In contrast, sirolimus-eluting stents perform optimally only when drug release is slow. The results offer explanations for recent trends in the development of DES and demonstrate the potential for large improvements in DES design relative to the current state of commercial devices.

Highlights

  • Drug-eluting stents (DES) have proven highly effective in reducing restenosis rates relative to bare metal stents

  • We show that optimizing the period of drug release from DES and the initial drug concentration within the coating has a drastic effect on DES performance

  • The design variables are assumed to be the initial drug concentration loaded onto the stent and the drug release rate from the stent coating

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Summary

Introduction

Drug-eluting stents (DES) have proven highly effective in reducing restenosis rates relative to bare metal stents. A persistent concern associated with the use of DES is late stent thrombosis, which can occur up to several years after stent implantation [1,2,3]. Its development remains incompletely understood, late stent thrombosis is thought to occur as a result of the delayed healing of the endothelium following its denudation by both the stent and the balloon upon which the stent is typically deployed. In support of this notion, a recent study. Bare metal stents are typically covered with new endothelium within six months of the stenting procedure [4, 5]

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