Fluorocopolymer-coated nitinol self-expanding paclitaxel-eluting stent: pharmacokinetics and vascular biology responses in a porcine iliofemoral model.

AIMS: Our aim was to evaluate arterial responses to paclitaxel and a novel fluorocopolymer-coated nitinol low-dose paclitaxel-eluting stent (FP-PES). METHODS AND RESULTS: Human smooth muscle cell (SMC) migration was assessed after exposure to paclitaxel in vitro. For pharmacokinetics and vascular response, FP-PES or bare metal stents (BMS) were implanted in porcine iliofemoral arteries. Paclitaxel significantly inhibited human coronary and femoral artery SMC migration at doses as low as 1 pM. Inhibition was significantly greater for femoral compared with coronary artery SMCs from 1 pM to 1 µM. Pharmacokinetics showed consistent paclitaxel release from FP-PES over the study duration. The peak arterial wall paclitaxel level was 3.7 ng/mg at 10 days, with levels decreasing to 50% of peak at 60 days and 10% at 180 days. Paclitaxel was not detected in blood or remote organs. Arteriogram and histomorphometry analyses showed FP-PES significantly inhibits neointimal proliferation versus BMS at 30 and 90 days. Re-endothelialisation scores were not different between groups. CONCLUSIONS: Paclitaxel affected femoral artery SMC migration at lower concentrations and to a greater degree than it did coronary artery SMCs. The novel FP-PES used in this preclinical study demonstrated a vascular healing response similar to BMS, while significantly inhibiting neointimal formation up to 90 days.

Vascular response to a third generation everolimus-eluting stent.

AIMS: In a non-injured porcine coronary artery model, the aim was to evaluate vascular compatibility of the novel platinum chromium everolimus-eluting PROMUS Element stent as compared to the following control stents: everolimus-eluting PROMUS (XIENCE V), bare metal Element, and polymer-only Element. METHODS AND RESULTS: Stent pairs (n=228) evenly distributed among the four stent types were implanted in overlap configuration in 79 pigs at a targeted stent-to-artery ratio of 1.1:1. Similar numbers were explanted at each of 7, 30, 90, 180, and 270 days for pathological analysis. No stent-related mortality or morbidity was observed. There were no stent occlusions or strut fractures. The PROMUS Element was more radiopaque than PROMUS (relative densities 9.9 and 9.1, respectively) and demonstrated at all time points vascular compatibility similar to that of the control stents for endothelial cell coverage, inflammatory response, and neointima formation. At 30 days, parastrut fibrin was mild but greater (P<0.0001) for the drug-eluting stents than either for the bare metal or the polymer-only Element; however, by 90 days the fibrin had dissipated. CONCLUSIONS: In the non-injured porcine coronary artery model, the PROMUS Element demonstrated vascular compatibility equivalent to PROMUS and the bare metal and polymer-only stents.