Main Session: The pathologist’s viewpoint, an update, 165001.
Vienna, Austria, 3 September 2007:
The current FDA approved stents (CYPHER and TAXUS) have been associated with late stent thrombosis (LST) (>30days following implantation) however, the mechanisms predictive of LST are poorly understood. Pathologic studies are one of the best methods for detailed analysis of morphologic changes that occur after placement of Drug Eluting Stents to determine the causes of LST. We have studies at autopsy 83 patients (117 lesions) with DES in place for > 30 days implanted in patients with coronary artery disease. Of 33 lesions with either luminal thrombus (n=25 lesions) or organized thrombus (n=8 lesions) 6 lesions (5 patients) showed a hypersensitivity reaction (5 Cypher and 1 Taxus).
These stent had been in place from 112 to 940 days; three patient died suddenly and two presented with acute myocardial infarction. From these data it appears that the response is limited to the area of the stent and that there is extensive eosinophilic and T-cell infiltration. There may or may not be a granulomatous reaction.
Other morphologic changes that predispose stent thrombosis are malapposition (n=8), stenting of bifurcation lesions (n=7), AMI patients (n=8), and overlapping stents (n=4). All showed delayed healing, which is further exaggerated either from turbulent flow at malapposition or bifurcation sites or poor healing at sites of plaque rupture, and overlapping stents. Excessive length (>30 mm) is a correlate of LST as well as presence of uncovered stent struts. Uniformly all cases with thrombi have presence of fibrin, poor stent coverage by neointima, and less endothelialization.
All 78 lesions that were patent (and DES was not the cause of death) and had been in place for >30 days showed less neointima as compared to bare metal stents (BMS) thus suggesting that DES are effective in reducing neointimal thickness. A parameter, which is uniformly observed in BMS is that the neointimal formation (smooth muscle cells in matrix) around the circumference of the stent tends to be uniform in distribution. In DES there is heterogeneity of healing with areas showing excessive fibrin and others with smooth muscle cells within matrix and uneven luminal endothelialization.
Cypher and Taxus stents although use different drug and coatings, both reduce neointimal formation from delayed healing. However, there are inherent differences in the response to each of the stents in man with fibrin deposition being more frequent in Taxus stent while inflammation especially eosinophilic infiltrate and giant cell reaction being greater in the Cypher stent.
One can conclude from these histologic studies that because of underlying atherosclerotic plaque morphology differences, variability in healing from patient to patient, and a hypersensitivity in some patients; DES technology may have to be tailored to individual patient characteristics, rather than one stent fits all.