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 language||English (US)|
|Number of pages||9|
|State||Published - Sep 2008|
- Catheter-based stent placement
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine