Author + information
- Received July 2, 2007
- Revision received April 23, 2008
- Accepted April 29, 2008
- Published online July 29, 2008.
- Michael Joner, MD⁎,
- Gaku Nakazawa, MD†,
- Aloke V. Finn, MD‡,
- Shawn Chin Quee, MS§,
- Leslie Coleman, DVM§,
- Eduardo Acampado, DVM†,
- Patricia S. Wilson, BA†,
- Kristi Skorija, BS†,
- Qi Cheng, MD†,
- Xin Xu, PhD†,
- Herman K. Gold, MD∥,
- Frank D. Kolodgie, PhD† and
- Renu Virmani, MD, FACC†,¶,⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. Renu Virmani, CVPath, Institute, Inc., 19 Firstfield Road, Gaithersburg, Maryland 20878.
Objectives The purpose of this study was to assess trends in endothelial coverage and recovery among leading polymer-based drug-eluting stents (DES).
Background Autopsy studies of human U.S. Food and Drug Administration (FDA)–approved DES implanted coronary arteries suggest that complications of late stent thrombosis are associated with incomplete endothelial coverage of struts.
Methods Rabbits received sirolimus-eluting stents (SES), paclitaxel-eluting stents (PES), zotarolimus-eluting stents (ZES), and everolimus-eluting stents (EES) for 14 or 28 days along with MULTI-LINK (ML) Vision control stents. Endothelial coverage above and between struts was measured by morphometric analysis of images acquired through en face scanning electron microscopy. Dual fluorescent immunolabeling was performed for platelet-endothelial cell adhesion molecule (PECAM)-1 and thrombomodulin (TM), factors involved in cell-to-cell contact and thrombogenicity, respectively. In a separate analysis, the endothelial mitogen, vascular endothelial growth factor (VEGF), was also assessed.
Results Varying rates of endothelialization among comparator DES were most notable at 14 days, where coverage above struts remained poor in SES, PES, and ZES (≤30%) relative to EES and ML Vision controls (≥70%), whereas no significant differences were observed at 28 days. Select DES with poor endothelialization showed a further reduced expression of PECAM-1. All DES showed an absence or weak expression of the antithrombotic cofactor TM. Incomplete endothelialization in select DES was further associated with increased VEGF secretion and messenger ribonucleic acid levels at 14 days, providing evidence of a transitional healing surface.
Conclusions The present study marks the first comparator analysis of endothelial coverage in leading polymeric DES, supporting disparities in arterial healing based on endothelial regrowth and recovery, favoring newer designs over the current generation of FDA-approved stents.
- drug-eluting stents
- platelet-endothelial adhesion molecule-1
- vascular endothelial growth factor
This study is supported in part by a grant from Abbott Vascular, Santa Clara, California. Dr. Virmani has received company-sponsored research support from Medtronic AVE, Abbott Vascular, W.L. Gore, Atrium Medical Corporation, Boston Scientific, NDC Cordis Corporation, Novartis, Orbus Medical Technologies, Biotronik, BioSensors, Alchimer, and Terumo, and is a consultant for Medtronic AVE, Guidant, Abbott Laboratories, W.L. Gore, Terumo, and Volcano Therapeutics Inc. Drs. Chin Quee and Coleman are employees of Abbott Vascular, Santa Clara, California. Drs. Joner and Nakazawa contributed equally to this article.
- Received July 2, 2007.
- Revision received April 23, 2008.
- Accepted April 29, 2008.
- American College of Cardiology Foundation