Background Stent thrombosis is a lethal complication of endovascular intervention. Concern has been raised for the inherent risk associated with specific stent designs and drug-eluting coatings, yet clinical and animal support are equivocal. Methods and Results We examined whether drug-eluting coatings are inherently thrombogenic and if the response to these materials was determined to a greater degree by stent design and deployment using custom-built stents. Drug/polymer coatings uniformly reduce rather than increase thrombogenicity relative to matched bare-metal counterparts (0.65-fold, p=0.011). Thick-strutted (162 μm) stents were 1.5-fold more thrombogenic than otherwise identical thin-strutted (81 μm) devices in ex vivo flow loops (p<0.001), commensurate with 1.6-fold greater thrombus coverage three days after implantation in porcine coronary arteries (p=0.004). When bare-metal stents were deployed in malapposed or overlapping configurations, thrombogenicity increased compared to apposed, length-matched controls (1.58-fold, p=0.001 and 2.32-fold, p<0.001). The thrombogenicity of polymer-coated stents with thin struts was lowest in all configurations and remained insensitive to incomplete deployment. Computational modeling-based predictions of stent-induced flow derangements correlated with spatial distribution of formed clots. Conclusions Contrary to popular conception drug/polymer coatings do not inherently increase acute stent clotting – they reduce thrombosis. However, strut dimensions and positioning relative to the vessel wall are critical factors in modulating stent thrombogenicity. Optimal stent geometries and surfaces, as demonstrated with thin stent struts, help reduce the potential for thrombosis despite complex stent configurations and variability in deployment.

Aims We sought to evaluate the incidence of embolic material in porcine brain following vascular interventions using hydrophilic-coated sheaths. Methods and results A new self-expanding stent and delivery system (SDS) were deployed through a hydrophilic-coated (Cook® Flexor Ansel) Guiding Sheath into iliac and/or carotid arteries of 23 anesthetized Yucatan miniswine. Animals were euthanized at 3, 30, 90 and 180 days and brains were removed for histological analysis. In an additional single control animal, the guiding sheath was advanced but no SDS was deployed. Advancement of the coated guiding sheath with or without the SDS was associated with frequent foreign material in the arterioles of the brain. The embolic material was amorphous, non-refractile, non-crystalline, and non-birefringent and typically lightly basophilic with a slight stippled appearance on hematoxylin and eosin (H&E) stain. Material was observed at all time points involving 54% of all study animals (ie, test and control) and in vitro after incubation in 0.9% saline. Conclusions The hydrophilic coating on a clinically used guiding sheath readily avulses and embolizes to the brain during deployment in a porcine model. Further documentation of this effect and monitoring in clinical scenarios is warranted.

Sex-related differences have been noted in cardiovascular anatomy, pathophysiology, and treatment responses, yet we continued to drive evaluation of vascular device development in animal models without consideration of animal sex. We aimed to understand sex-related differences in the vascular responses to stent implantation by analyzing the pooled data of endovascular interventions in 164 Yucatan mini-swine (87 female, 77 male). Bare metal stents (BMS) or drug-eluting stents (DES) were implanted in 212 coronary arteries (63 single BMS implantation, 68 single DES implantation, 33 overlapped BMS implantation, and 48 overlapped DES implantation). Histomorphological parameters were evaluated from vascular specimens at 3–365 days after stent implantation and evaluated values were compared between female and male groups. While neointima formation at all times after implantation was invariant to sex, statistically significant differences between female and male groups were observed in injury, inflammation, adventitial fibrosis, and neointimal fibrin deposition. These differences were observed independently, i.e., for different procedure types and at different follow-up timings. Only subtle temporal sex-related differences were observed in extent and timing of resolution of inflammation and fibrin clearance. These subtle sex-related differences may be increasingly important as interventional devices meld novel materials that erode and innovations in drug delivery. Erodible materials may act differently if inflammation has a different temporal sequence with sex, and drug distribution after balloon or stent delivery might be different if the fibrin clearance speaks to different modes of pharmacokinetics in male and female swine.