Introducing the first polymer-free leflunomide eluting stent

Aims: 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 40mM 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 Tomografies (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 1–100nM (p=NS L vs. R). Interestingly, human EC proliferation at 10–100nM 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.