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      Drug deposition in coronary arteries with overlapping drug-eluting stents

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          Drug-eluting stents are accepted as mainstream endovascular therapy, yet concerns for their safety may be under-appreciated. While failure from restenosis has dropped to below 5%, the risk of stent thrombosis and associated mortality remain relatively high. Further optimization of drug release is required to minimize thrombosis risk while maintaining therapeutic dose.

          The complex three-dimensional geometry of deployed stents together with the combination of diffusive and advective drug transport render an intuitive understanding of the situation exceedingly difficult. In situations such as this, computational modeling has proven essential, helping define the limits of efficacy, determine the mode and mechanism of drug release, and identify alternatives to avoid toxicity.

          A particularly challenging conformation is encountered in coronary arteries with overlapping stents. To study hemodynamics and drug deposition in such vessels we combined high-resolution, multi-scale ex vivo computed tomography with a flow and mass transfer computational model. This approach ensures high geometric fidelity and precise, simultaneous calculation of blood flow velocity, shear stress and drug distribution.

          Our calculations show that drug uptake by the arterial tissue is dependent both on the patterns of flow disruption near the wall, as well as on the relative positioning of drug-eluting struts. Overlapping stent struts lead to localized peaks of drug concentration that may increase the risk of thrombosis. Such peaks could be avoided by anisotropic stent structure or asymmetric drug release designed to yield homogeneous drug distribution along the coronary artery and, at the least, suggest that these issues need to remain in the forefront of consideration in clinical practice.

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          Author and article information

          J Control Release
          J Control Release
          Journal of controlled release : official journal of the Controlled Release Society
          26 July 2016
          16 July 2016
          28 September 2016
          28 September 2017
          : 238
          : 1-9
          [a ]Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA
          [b ]Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
          [c ]The Interface Group, Institute of Physiology, University of Zurich, Zurich, Switzerland
          [d ]Laboratory of Thermodynamics in Emerging Technologies, Department of Mechanical and Process Engineering, ETH Zurich, Zurich, Switzerland
          [e ]Zurich Center for Integrative Human Physiology and National Center of Competence ‘Kidney.CH’, University of Zurich, Zurich, Switzerland
          Author notes
          Corresponding Author: Farhad Rikhtegar, Harvard-MIT Biomedical Engineering Center, 77 Massachusetts Avenue, Building E25-449, Cambridge, MA 02139. USA, farhadr@ 123456mit.edu , Phone: +1 (617) 258 88 94, Fax: +1 (617) 258 25 14
          PMC5014575 PMC5014575 5014575 nihpa805243


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