Particle debris from a nanoporous stent coating obscures potential antiproliferative effects of tacrolimus-eluting stents in a porcine model of restenosis

• Published in: Catheterization and cardiovascular interventions 2005-01, Vol.64 (1), p.85-90
• Main Authors: Kollum, Marc, Farb, Andrew, Schreiber, Ralf, Terfera, Kirubel, Arab, Amina, Geist, Andrea, Haberstroh, Jörg, Wnendt, Stephan, Virmani, Renu, Hehrlein, Christoph
• Format: Article
• Language: English
• Subjects: Aluminum Oxide - pharmacology; Animals; Coated Materials, Biocompatible - pharmacology; Coronary Restenosis - prevention & control; drug-eluting stent; Graft Occlusion, Vascular - prevention & control; Hyperplasia; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - pharmacology; inflammation; Prosthesis Design; restenosis; Stents - adverse effects; Swine; tacrolimus; Tacrolimus - administration & dosage; Tacrolimus - pharmacology; Tunica Intima - drug effects; Tunica Intima - pathology
• ISSN: 1522-1946; 1522-726X
• DOI: 10.1002/ccd.20213

Polymer stent coatings may not be suitable for drug elution because of inherent proinflammatory effects. A previous study suggested a beneficial effect of a stent eluting tacrolimus from a nanoporous ceramic aluminum oxide coating in a rabbit restenosis model. We investigated whether this stent is effective in preventing in‐stent restenosis in a porcine restenosis model. Thirty‐four juvenile swine underwent balloon overstretch injury and were subjected to implantation of either stainless steel (bare) stents, bare stents coated with nanoporous aluminum oxide alone, and coated stents eluting 50 and 180 μg of tacrolimus (FK506). In‐stent restenosis was quantified at 1 and 3 months after stent placement by histomorphometry. A significant increase of neointimal hyperplasia was noted with the stents coated with aluminum oxide alone compared with bare stents (2.92 ± 1.02 and 1.38 ± 0.51 mm2, respectively; P < 0.02). In all arteries containing coated stents, particle debris was found in the media and neointima, resulting in augmented vascular inflammation. In the group of stents coated with aluminum oxide, FK506 elution at a dose 180 μg reduced neointimal hyperplasia vs. no drug elution (1.66 ± 0.49 vs. 2.92 ± 1.02 mm2; 180 μg vs. ceramic alone; P < 0.03). At a dose of 50 μg stent‐based delivery of FK506, no reduction of neointimal hyperplasia was found (2.88 ± 1.31 and 2.92 ± 1.02 mm2, respectively; P = NS; FK506 vs. ceramic alone). In summary, particle debris shed from a drug‐eluting aluminum oxide coating of a stainless steel stent counteracts potential antiproliferative effects of stent‐based tacrolimus delivery in a porcine model of restenosis. We propose that stent coatings eluting drugs need to be routinely tested for being tightly anchored into the stent surface. Alternatively, omission of any coating used as a drug reservoir may eliminate inflammatory particle debris after placement of drug‐eluting stents. Catheter Cardiovasc Interv 2005;64:85–90. © 2004 Wiley‐Liss, Inc.