European Heart Journal Advance Access originally published online on January 31, 2006
European Heart Journal 2006 27(8):988-993; doi:10.1093/eurheartj/ehi752
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Zotarolimus-eluting stents reduce experimental coronary artery neointimal hyperplasia after 4 weeks
1Minneapolis Heart Institute and Foundation, Minneapolis Heart Institute, 920 E. 28th St., Suite 620, Minneapolis, MN 55407, USA
2Abbott Laboratories, Abbott Park, IL 60064, USA
Received 14 January 2005; revised 15 December 2005; accepted 12 January 2006; online publish-ahead-of-print 31 January 2006.
* Corresponding author. Tel: +1 612 863 3913; fax: +1 612 863 3784. E-mail address: rss{at}rsschwartz.com
Aims The addition of drug elution to coronary stents plays an integral role in coronary restenosis prevention. The present study was undertaken to determine the mechanism of action and the in vitro and in vivo efficacy of zotarolimus, a new chemical entity designed specifically for elution from phosphorylcholine (PC)-coated stents, for the reduction of neointimal hyperplasia in porcine coronary arteries.
Methods and results In vitro studies of Zotarolimus bound to FKBP-12 potently inhibited smooth muscle cells (SMCs) and endothelial cell (EC) proliferation. Twenty PC-only and 20 stents eluting zotarolimus 10 µg/mm were implanted in the coronary arteries of 20 domestic juvenile swine. After 28 days, zotarolimus stents exhibited less area stenosis (22.4±8.6 vs. 35.7±13%, P=0.01), less neointimal area (1.69±0.55 vs. 2.78±1.07 mm2, P=0.01), less neointimal thickness (0.25±0.07 vs. 0.38±0.13 mm, P=0.01), and greater lumen area (6.07±1.39 vs. 5.02±1.3 mm2, P=0.01). All arteries in both the polymer-only and polymer/drug stent showed near-complete healing and minimal toxicity. Zotarolimus did not affect the extrastent segments nor alter the overall artery size (external elastic lamina cross-sectional area 9.18±1.19 vs. 9.06±1.28 mm2, P=0.7).
Conclusion Zotarolimus binds to FKBP-12 and in vitro inhibits SMC and EC proliferation. Zotarolimus applied to PC-coated stents reduces neointima in the swine coronary model after 28 days. These results suggest potentially promising human clinical application for coronary stenting with this polymer/drug combination.
Key Words: Stents • Restenosis • Zotarolimus • Phosphorylcholine
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