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European Heart Journal Advance Access published online on April 12, 2007
European Heart Journal, doi:10.1093/eurheartj/ehm064
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© The European Society of Cardiology 2007. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Drug-eluting stents show delayed healing: paclitaxel more pronounced than sirolimus

Heleen M.M. van Beusekom1,*, Francesco Saia1, Jaap D. Zindler1, Pedro A. Lemos1, Stijn L. Swager-ten Hoor1, Maarten A.H. van Leeuwen1, Pim J. de Feijter1, Patrick W. Serruys1 and Willem J. van der Giessen1,2

1 Department of Cardiology, Ee 2355b, Erasmus Medical Center Rotterdam, Dr. Molewaterplein 50, PO Box 1738, 3000 Rotterdam, The Netherlands
2 Interuniversity Cardiology Institute (ICIN), Utrecht, The Netherlands

Received 7 June 2006; revised 7 February 2007; accepted 8 March 2007.

* Corresponding author. Tel: +31 10 4088048; fax: +31 10 4089494. E-mail address: h.vanbeusekom{at}erasmusmc.nl

Aims: To understand wound healing after drug-eluting stents (DES) placement in humans, we studied the histology of in-stent restenosis (ISR) tissue obtained by atherectomy from bare metal stents (BMS) and DES in comparison with de novo atherosclerosis.

Methods and results: The tissue was retrieved from ISR in ten sirolimus-eluting stents (SES) and nine paclitaxel-eluting stents (PES), six BMS, and nine stenotic de novo atherosclerotic lesions and processed for histology and immunocytochemistry. Patients with ISR in PES showed a significantly higher incidence of unstable angina upon presentation for re-intervention (P = 0.046). De novo tissue tended to be more collagen rich, whereas ISR tissue tended to be more proteoglycan rich. In all groups, cell content consisted almost exclusively of smooth muscle cells. Histology showed that fibrinoid in ISR tissue was present only in DES (P = 0.004), as late as 2 years following DES placement, indicating a persistent incomplete healing response. The amount of fibrinoid, given as a percentage of total tissue in each atherectomy specimen, was greater in PES than in SES (17 vs. 5%, P = 0.026).

Conclusion: ISR in DES shows incomplete neointimal healing as late as 2 years after implantation. Patients with ISR in PES presented with more unstable angina and showed more pronounced signs of delayed healing than SES.

Key Words: Drug-eluting stent • Restenosis • Delayed healing • Pathology • Atherectomy


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