Introducing the first polymer-free leflunomide eluting stent

Tobias Deuse, Reinhold G. Erben, Fumiaki Ikeno, Boris Behnisch, Rainer Boeger, Andrew J. Connolly, Hermann Reichenspurner, Claudia Bergow, Marc P. Pelletier, Robert C. Robbins, Sonja Schrepfer

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Background: We here describe the pharmacological characteristic, in vivo efficacy, and in vitro mechanisms of a polymer-free leflunomide eluting stent in comparison to its rapamycin-coated equivalent. Methods: Stents were coated with 40 mM solutions of leflunomide (L) or rapamycin (R) or were left uncoated (BM). Neointima formation was assessed 6 weeks after implantation into Sprague Dawley rats by optical coherence tomographies (OCT) and histopathology. In vitro proliferation assays were performed using isolated endothelial and smooth-muscle-cells from Sprague Dawley rats to investigate the cell-specific pharmacokinetic effect of leflunomide and rapamycin. Results: HPLC-based drug release kinetics revealed a similar profile with 90% of the drug being released after 12.1 ± 0.2 (L) and 13.0 ± 0.2 days (R). After 6 weeks, OCTs showed that in-stent luminal obliteration was less for the coated stents (L:12.0 ± 9.4%, R:13.3 ± 13.1%) when compared to identical bare metal stents (BM:26.4 ± 4.7%; p ≤ 0.046). Histology with computer-assisted morphometry was performed and demonstrated reduced in-stent I/M thickness ratios (L:2.5 ± 1.2, R:3.7 ± 3.3, BM:6.7 ± 2.3, p ≤ 0.049 for L and R vs. BM) and neointimal areas (L:0.6 ± 0.3, R:0.7 ± 0.2, BM:1.3 ± 0.4, p ≤ 0.039 for L and R vs. BM) with stent coating. No differences were found for injury and inflammation scores (L and R vs. BM; p = NS). In vitro SMC proliferation was dose-dependently and similarly inhibited by L and R at 1-100 nM (p = NS L vs. R). Interestingly, human EC proliferation at 10-100 nM was significantly inhibited only by R (p < 0.001), but not by L (p = NS). Conclusions: The diminished inhibition of EC proliferation may improve arterial healing and contribute to the safety profile of the leflunomide stent.

Original languageEnglish (US)
Pages (from-to)126-134
Number of pages9
JournalAtherosclerosis
Volume200
Issue number1
DOIs
StatePublished - Sep 2008
Externally publishedYes

Keywords

  • Catheter-based stent placement
  • Leflunomide
  • Restenosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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