Impact of Heterogeneous Overlapping Drug-Eluting Stents on the Arterial Responses of Rabbit Iliac Arteries: A Comparison With Overlapping Bare Metal Stents

Background and Objectives: Although the use of heterogeneous overlapping drug-eluting stents (DES) is not uncommon in clinical practice, whether the implantation sequences of heterogeneous DES will influence the endothelialization or arterial responses differently remains unclear. Materials and Methods: Twenty-one rabbits were randomized to receive overlapping stents in the iliac artery for 3 months {distal sirolimuseluting stent (SES, $Cypher^{TM}$)+proximal paclitaxel-eluting stent (PES, $Taxus^{TM}$) (C+T, n=7), distal Taxus+proximal Cypher (T+C, n=7) and bare metal stent (BMS)+BMS (B+B, n=7)}. Endothelial function was evaluated by the acetylcholine provocation test during follow-up angiography. Histopathological changes in proximal, overlapped, and distal stented segments were evaluated. Results: Although the overall angiographic outcomes were comparable, late loss (mm) in the distal stented segment was higher in the B+B (0.39${\pm}$0.07) and C+T (0.40${\pm}$0.20) than that in the T+C (0.06${\pm}$0.02) group (p<0.001). The incidence of acetylcholine-induced spasm was higher in the DES groups compared with BMS, regardless of the implantation sequences (85.7% in C+T vs. 14.3% in B+B vs. 71.4% in T+C, p=0.017). Notably, only the distal Cypher implantation group (C+T) had three cases of stent fracture. A histopathological analysis showed that despite similar arterial injury scores, Taxus and Cypher stents had higher inflammatory reactions at the overlapped and distal segments compared with those of BMS. Conclusion: Despite similar arterial injury, higher inflammatory reactions were observed in overlapping DES segments regardless of the implantation sequence compared with that of BMS. Moreover, DES was associated with impaired endothelial function on the adjacent nonstented segments.