Pathology of First-generation Drug-eluting Stents in Humans

First-generation sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) have dramatically reduced restenosis, although concern still exists about the long-term safety of this technology since observational studies have shown a steady increase in the rate of late stent thrombosis (LST), an infrequent but catastrophic complication. Although the mechanisms of LST are multifactorial, our laboratory has demonstrated that delayed arterial healing accompanied by poor endothelialisation is the primary pathogical substrate underlying this event. Delayed arterial healing is associated with penetration of necrotic core, long/overlapping stents and bifurcation stenting, especially in flow divider (high shear) regions. Grade V stent fracture is also associated with adverse pathogical findings including LST and restenosis. Moreover, localised hypersensitivity reaction is exclusive to SES as an underlying mechanism of LST, while malapposition secondary to excessive fibrin deposition is associated with PES. Uncovered struts are still identified in both SES and PES with implant duration beyond 12 months, particularly in stents placed for ‘off-label’ indications. In conclusion, the first generation of drug-eluting stents (DES) certainly reduce neointimal growth but this comes at the price of delayed healing.