Pathological Correlates of Late Drug-Eluting Stent Thrombosis

Abstract

Background-Late stent thrombosis (LST) after Cypher and Taxus drug-eluting stent placement has emerged as a major concern. Although the clinical predictors of LST have been reported, specific morphological and histological correlates of LST remain unknown. Methods and Results-From a registry totaling 81 human autopsies of drug-eluting stents, 46 (62 lesions) had a drug-eluting stent implanted Ͼ30 days. We identified 28 lesions with thrombus and compared those with 34 of similar duration without thrombosis using computer-guided morphometric and histological analyses. LST was defined as an acute thrombus within a coronary artery stent in place Ͼ30 days. Multiple logistic generalized estimating equations modeling demonstrated that endothelialization was the best predictor of thrombosis. The morphometric parameter that best correlated with endothelialization was the ratio of uncovered to total stent struts per section. A univariable logistic generalized estimating equations model of occurrence of thrombus in a stent section versus ratio of uncovered to total stent struts per section demonstrated a marked increase in risk for LST as the number of uncovered struts increased. The odds ratio for thrombus in a stent with a ratio of uncovered to total stent struts per section Ͼ30% is 9.0 (95% CI, 3.5 to 22). Conclusions-The most powerful histological predictor of stent thrombosis was endothelial coverage. The best morphometric predictor of LST was the ratio of uncovered to total stent struts. Heterogeneity of healing is a common finding in drug-eluting stents with evidence of LST and demonstrates the importance of incomplete healing of the stented segment in the pathophysiology of LST.

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

“…As the previous studies reported, reendothelialization following stent implantation is very important to prevent stent thrombosis3, 4 because the exposure of stent strut surfaces to the bloodstream may result in thrombus formation 16. Synergy showed the fastest neointimal coverage in atherosclerotic rabbits among the DESs investigated.…”

“…All animals were premedicated with oral aspirin (40 mg/day) 2 days before the procedure 4, 16, 17. Rabbits were anesthetized with 2.5% isoflurane via facemask.…”

“…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.…”

Late stent thrombosis, endothelialisation and drug-eluting stents

“…4,16,17 Indeed, Finn and colleagues reported incomplete neointimal coverage of stent struts as the most important morphometric predictor of LST. 4 However, the unexplained variation was high (1-r 2 =81.5%), and the results may not be representative of patients who receive DES and survive.…”

“…3 This concept is based on clinical autopsy studies and clinical intracoronary angioscopy studies. 4,5 However we feel this concept is still open to debate. Our hypothesis is that delayed re-endothelialisation alone is not adequate to explain LST.…”