Introducing the first polymer-free leflunomide eluting stent

Atherosclerosis. 2008 Sep;200(1):126-34. doi: 10.1016/j.atherosclerosis.2007.12.055. Epub 2008 Mar 4.


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<or=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<or=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<or=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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Drug-Eluting Stents*
  • Endothelial Cells / drug effects
  • Enzyme Inhibitors / pharmacokinetics
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Isoxazoles / pharmacokinetics
  • Isoxazoles / pharmacology*
  • Leflunomide
  • Myocytes, Smooth Muscle / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Sirolimus / pharmacokinetics
  • Sirolimus / pharmacology
  • Tomography, Optical Coherence
  • Tunica Intima / drug effects*
  • Tunica Intima / pathology
  • Tunica Media / drug effects*
  • Tunica Media / pathology


  • Enzyme Inhibitors
  • Isoxazoles
  • Leflunomide
  • Sirolimus