title: Pathophysiology of vascular healing and stent mediated arterial injury.
abstract: Drug eluting stents (DES) have expanded the use of stents for the treatment of coronary atherosclerotic disease with significant reduction in restenosis rates. However, DES have been associated with late stent thrombosis (LST), especially when used for "off-label" indications. Although similar cellular processes control the early response after both bare metal (BMS) and DES placement, the more chronic response and time course of healing is markedly different between BMS and DES. There is persistence of fibrin beyond the 12-month period and re-endothelialisation is incomplete with some struts remaining uncovered beyond the 2-year period, a strong predictor for LST. While vessel wall injury correlated with restenosis in the BMS era, its impact has been minimised by the use of DES, which is likely related to the use of powerful antiproliferatives with prolonged release kinetics which profoundly inhibit the reparative response to arterial injury. However, at the same time, vessel injury secondary to drug toxicity or inflammation caused by polymer is observed following DES implantation. Nonerodable polymers induce granulomatous and hypersensitivity reactions in animal models and this has been observed exclusively with the use of Cypher stents in man. On the other hand the Taxus stent is associated with medial necrosis, positive remodelling and excessive fibrin deposition, all likely cytotoxic effects of paclitaxel. Both may lead to late stent thrombosis. Other factors that increase risk are penetration of the necrotic core, bifurcation stenting and malapposition.
authors.affiliation: CVPath Institute, Inc., Gaithersburg, Maryland, USA.
authors.forename: Gaku
authors.initials: G
authors.lastname: Nakazawa
authors.forename: Elena
authors.initials: E
authors.lastname: Ladich
authors.forename: Aloke V
authors.initials: AV
authors.lastname: Finn
authors.forename: Renu
authors.initials: R
authors.lastname: Virmani
mesh_terms: D002986:Clinical Trials as Topic; D003331:Coronary Vessels / Q000473:pathology*; D054855:Drug-Eluting Stents / Q000009:adverse effects*; D006801:Humans; D013927:Thrombosis / Q000209:etiology; D014945:Wound Healing