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Lowering the Dose of Sirolimus, Released From a Nonpolymeric Hydroxyapatite Coated Coronary Stent, Reduces Signs of Delayed Healing

Wim J. van der Giessen, MD, PhD^_*,, Oana Sorop, PhD^_*, Patrick W. Serruys, MD, PhD^_*, Ilona Peters-Krabbendam, BSc^_*, Heleen M.M. van Beusekom, PhD^_*,_*

^_* Department of Cardiology, Erasmus Medical Center, Rotterdam, the Netherlands
Interuniversity Cardiology Institute-KNAW, Utrecht, the Netherlands

^_* Reprint requests and correspondence: Dr. Heleen van Beusekom, Thoraxcenter, Room Ee2393a or 2355a, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, the Netherlands (Email: h.vanbeusekom{at}erasmusmc.nl).

Objectives: The aim of this study was to compare efficacy of low- and high-dose sirolimus release (25, 40, or 100 µg) from hydroxyapatite (HAp) with Cypher (Cordis, Johnson & Johnson, Warren, New Jersey) (111 µg sirolimus) in porcine coronary arteries.

Background: Polymer-based sirolimus-eluting stents such as Cypher interfere with vascular healing, probably due to the permanent presence of the polymer coating and the high sirolimus dose. The use of low-dose sirolimus and inert nonpolymeric but biodegradable coatings such as HAp might be more appropriate.

Methods: Stents (n = 68) were implanted, guided by quantitative coronary angiography. All swine received clopidogrel and acetylsalicylic acid during 28 days follow-up. Safety of the coating in absence of drugs was studied by comparing HAp with and without a lipid-based release regulating layer (HApR) with bare-metal stents. Efficacy was studied by comparing the release of 25, 40, and 100 µg sirolimus with Cypher.

Results: The safety study (without drug) revealed no differences in neointimal thickening in response to HAp and HApR with complete healing in all groups. Dose response analysis showed that neointimal thickening was similar in all groups regardless of sirolimus dose, with a normal appearance of the endothelium. There was, however, a dose-dependent increase in fibrinoid (p = 0.028), considered to be a marker of delayed healing. The Cypher stent induced the highest amount of fibrinoid.

Conclusions: Reducing the dose of sirolimus eluting from a biocompatible HAp coated stent reduces signs of delayed vascular healing, without affecting neointimal hyperplasia.

Key Words: animal model • coronary • drug eluting stent • nonpolymeric coatings • PCI

Abbreviations and Acronyms   ASA = acetylsalicylic acid   DES = drug-eluting stent(s)   HAp = hydroxyapatite   HApR = hydroxyapatite including drug release regulating lipid layer   QCA = quantitative coronary angiography