The Pathology of Neoatherosclerosis in Human Coronary Implants

Abstract

Objectives Human coronary bare metal stents (BMS) and drug-eluting stents (DES) from autopsy cases with implant durations >30 days were examined for the presence of neointimal atherosclerotic disease. Background Neointimal atherosclerotic change (neoatherosclerosis) following BMS implantation is rarely reported and usually occurs beyond 5 years. The incidence of neoatherosclerosis following DES implantation has not been reported. Methods All available cases from the CVPath stent registry (n=299 autopsies), which includes a total of 406 lesions (197 BMS, 209 DES [103 sirolimus-eluting stents (SES), and 106 paclitaxel-eluting stents (PES)]) with implant duration >30 days were examined. Neoatherosclerosis was recognized as clusters of lipid-laden foamy macrophages within the neointima with or without necrotic core formation. Results The incidence of neoatherosclerosis was significantly greater in DES (31%) than BMS (16%) lesions (p<0.001). The median stent duration with neoatherosclerosis was shorter in DES than BMS (DES; 420 [361–683], BMS; 2160 [1800–2880] days, p<0.001). Unstable lesions characterized as thin-cap fibroatheromas or plaque rupture were more frequent in BMS (n=7, 4%) than DES (n=3, 1%) (p=0.17), with relatively shorter implant durations for DES (1.5±0.4 years) compared to BMS (6.1±1.5 years). Independent determinants of neoatherosclerosis identified by multiple logistic regression included younger age (p<0.001), longer implant durations (p<0.001), SES usage (p<0.001), PES usage (p=0.001), and underlying unstable plaques (p=0.004). Conclusions Neoatherosclerosis is a frequent finding in DES and occurs earlier than in BMS. Unstable features of neoatherosclerosis are identified for both BMS and DES with shorter implant durations for the latter. The development of neoatherosclerosis may be yet another rare contributing factor to late thrombotic events.

Downstream coronary effects of drug-eluting stents

“…[13][14][15] Recent studies also suggest that DESs may result in endothelial dysfunction manifested through impaired vascular responsiveness in the downstream vessel as well as contributing to late stent thrombosis through neoatherosclerosis. [16][17][18] However, several studies also suggest that cell-cycle inhibitors may possess antiatherogenic properties. [19][20][21][22][23] Although published data are conflicted, it appears that overall outcomes, including target vessel revascularization rates, are slightly more favorable in patients receiving DES, although this has to be weighed against higher stent costs and the necessity for prolonged, uninterrupted antiplatelet therapy.…”

“…Although these results demonstrate protection from lesion formation, toxicity of antiproliferative drugs still remains a concern, particularly in tissues affected by infarction because of the potential for inducing a thrombogenic state through platelet dysfunction as well as neoatherosclerosis. 18,31,39 Despite these uncertainties, our findings should encourage a clinical trial with advanced coronary imaging tools to further investigate the effects that DES have on atherosclerosis in downstream vessels.…”

Comparison of Vascular Responses Following New‐Generation Biodegradable and Durable Polymer‐Based Drug‐Eluting Stent Implantation in an Atherosclerotic Rabbit Iliac Artery Model

“…Although incomplete endothelialization was reported as the primary substrate of late stent thrombosis in an initial pathological study,3, 4 recent reports revealed that abnormal vascular responses are also responsible for the occurrence of late stent failure 5, 6, 7. Such abnormal responses include hypersensitivity reactions, extensive fibrin deposition along with malapposition, and neoatherosclerosis.…”

Optical Coherence Tomography Assessment of Glucose Fluctuation Impact on the Neointimal Proliferation After Stent Implantation in a Diabetic/Hypercholesterolemic Swine Model

“…In addition, recent studies suggest that the different characteristics of neointimal tissue seen by OCT may correlate with clinical events such as late stent thrombosis. 20) Kim, et al 21) compared different OCT morphological characteristics with different in-stent neointimal tissue types analyzed by histology and found that the homogeneous pattern of neointimal formation appeared to correlate with less neointimal formation and more favorable vessel healing characteristics when compared with the other optical patterns; the heterogeneous pattern correlated more with the presence of fibrin deposits than the other patterns; the layered pattern correlated with the higher incidence of peri-strut inflammation, neovascularization, and external elastic lamina rupture, which might lead to a higher degree of neointimal proliferation. In a clinical study, Tanaka, et al 22) concluded that in DM patients, the heterogeneous pattern was observed with high frequency.…”