Drug-Eluting Stent - Importance of Clinico-Pathological Correlations -

Abstract

he benefits of using drug-eluting stents (DES) for coronary artery diseases are widely accepted because of the remarkable reduction in the rates of restenosis and of target lesion revascularization (TLR) compared with bare-metal stents (BMS). 1,2 However, in-stent thrombosis (IST), a rare but tragic event, has been reported after DES implantation, 3 and the time course of thrombotic risk at the level of the DES-implanted vessels is longer than that observed after BMS. 4,5 Late IST, thrombosis occurring more than 30 days after stent implantation, and very late IST, occurring after more than 1 year, often have a catastrophic outcome. The pathogenesis of IST is probably multifactorial, 6 but the mechanisms are not fully elucidated. From the viewpoint of the pathologist, a foreign body reaction against DES in the coronary artery tree is clearly different from the corresponding lesions occurring after BMS. DES suppresses the early immune response of the treated artery compared with BMS. Furthermore, delayed arterial healing processes, such as incomplete endothelial cell covering and persistent fibrin deposition, have been identified after DES implantation and may play an important role in IST development. Our understanding of IST pathogenesis should be facilitated by knowledge of the pathological alterations in coronary arteries treated with DES devices. This review focuses on the histopathologic features after DES implantation in humans, especially on the initial cellular responses of the arterial wall. Action of Sirolimus and Paclitaxel on the Coronary Artery WallThe macrolide antibiotic, sirolimus, approved as an immunosuppressant to prevent organ rejection after transplantation therapy, also inhibits smooth muscle cell migration and proliferation, inducing reduction of neointimal thickening through its action on mammalian target of rapamycin and on the cyclin-dependent kinase inhibitor. 7-11 However, oral admin- The benefit of drug-eluting stents (DES) is the remarkable reduction in the rates of both restenosis and target lesion revascularization. However, the risk of thrombotic complications extends further in DES-implanted arteries compared with those treated with bare-metal stents (BMS). Moreover, in-stent thrombosis (IST) and delayed arterial healing in DES-treated arteries have been identified by histological examination. At autopsy, proliferation of a monolayer composed of endothelium-like cells over stent struts in DES receiving arteries has been observed; however, these cells are negative for well-accepted endothelial cell markers. An inflammatory reaction against the stent struts is apparent after implantation of BMS and paclitaxel-eluting stents, whereas after sirolimus-eluting stents (SES), minimal inflammation is seen up to 6 months after device implantation. IST and in-stent restenosis, both possibly related to a hypersensitivity phenomena, are peculiar to DES, albeit relatively infrequent. A case of enhanced neointimal hyperplasia at 6 months after SES implantation with massive inflammatory reaction...

Intravascular ultrasound and histopathological observations in a patient with very late sirolimus-eluting stent thrombosis

“…Sustained inflammation might be operative for both VLST and restenosis after DES implantation. Hao et al reported the coexistence of inflammatory reaction, persistent fibrin deposition, and neointimal hyperplasia in restenotic lesion after SES implantation [8]. These interesting findings suggested that sustained inflammation of coronary arterial wall could be concurrent with restenotic reaction after DES implantation.…”

Pathogenesis of late in-stent thrombosis after treatment with drug-eluting stents

“…Histological observation indicates that foreign body reaction against DES is clearly different from the corresponding lesions occurring after BMS implantation. In our experience of autopsy cases, first-generation DES suppresses the early immune response of the treated artery compared to BMS [7] . Furthermore, delayed arterial healing processes, such as incomplete endothelial cell covering, lack of intimal thickening, and persistent fibrin deposition have been identified after DES implantation ( Fig.…”