Long-Term Safety of an Everolimus-Eluting Bioresorbable Vascular Scaffold and the Cobalt-Chromium XIENCE V Stent in a Porcine Coronary Artery Model

Abstract

Background-The Absorb everolimus-eluting bioresorbable vascular scaffold (Absorb) has shown promising clinical results; however, only limited preclinical data have been published. We sought to investigate detailed pathological responses to the Absorb versus XIENCE V (XV) in a porcine coronary model with duration of implant extending from 1 to 42 months. Methods and Results-A total of 335 devices (263 Absorb and 72 XV) were implanted in 2 or 3 main coronary arteries of 136 nonatherosclerotic swine and examined by light microscopy, scanning electron microscopy, pharmacokinetics, and gel permeation chromatography analyses at various time points. Vascular responses to Absorb and XV were largely comparable at all time points, with struts being sequestered within the neointima. Inflammation was mild to moderate (with absence of inflammation at 1 month) for both devices, although the scores were greater in Absorb at 6 to 36 months. Percent area stenosis was significantly greater in Absorb than XV at all time points except at 3 months. The extent of fibrin deposition was similar between Absorb and XV, which peaked at 1 month and decreased rapidly thereafter. Histomorphometry showed expansile remodeling of Absorb-implanted arteries starting after 12 months, and lumen area was significantly greater in Absorb than XV at 36 and 42 months. These changes correlated with dismantling of Absorb seen after 12 months. Gel permeation chromatography analysis confirmed that degradation of Absorb was complete by 36 months. Conclusions-Absorb demonstrates comparable long-term safety to XV in porcine coronary arteries with mild to moderate inflammation. Although Absorb was associated with greater percent stenosis relative to XV, expansile remodeling was observed after 12 months in Absorb with significantly greater lumen area at ≥36 months. Resorption is considered complete at 36 months. (Circ Cardiovasc Interv. 2014;7:330-342.)

Comparison of a Drug‐Free Early Programmed Dismantling PDLLA Bioresorbable Scaffold and a Metallic Stent in a Porcine Coronary Artery Model at 3‐Year Follow‐Up

“…Inflammation was greater in ART‐BRS relative to BMS and peaked at 6 months, which likely reflects maximum decrease in molecular weight and release of soluble degradation products that coincide with luminal gain as a result of vascular remodeling. It has been reported inflammation is observed from 12 to 36 months in Absorb BVS with late lumen enlargement 7. The exact timing of inflammation likely varies in human disease conditions, where the early onset of inflammation in ART‐BRS relative to other contemporary BRS may allow for early remodeling.…”

“…All histologic sections were examined for inflammation, fibrin, giant cell reaction, and vessel injury as previously described 12. Strut discontinuities were defined as sites that showed deviation from the conventional box shape with integration of arterial derived tissue on a cross‐sectional level 7. Strut resorption sites were identified by the presence of a glassy appearance, with either eosinophilic or amphophilic staining by hematoxylin and eosin and under polarized light 7.…”

“…Strut discontinuities were defined as sites that showed deviation from the conventional box shape with integration of arterial derived tissue on a cross‐sectional level 7. Strut resorption sites were identified by the presence of a glassy appearance, with either eosinophilic or amphophilic staining by hematoxylin and eosin and under polarized light 7. Histomorphometry was performed using computer‐assisted software (IPLab, Scanalytics, Rockville, MD) as previously described 13…”

“…In addition, the Absorb BVS showed a significantly higher device‐oriented composite end point with higher incidence of scaffold thrombosis 5. Many BRSs have been investigated in preclinical studies,6, 7 where degradation kinetics have been variable. From these preclinical studies, it is clear that slow degradation of polymeric BRS was considered safe and was associated with mild inflammation 6, 7.…”

“…Many BRSs have been investigated in preclinical studies,6, 7 where degradation kinetics have been variable. From these preclinical studies, it is clear that slow degradation of polymeric BRS was considered safe and was associated with mild inflammation 6, 7. However, a more rapid onset of degradation may facilitate early vessel remodeling and luminal gain during the course of vascular healing and consequently may decrease detrimental vascular effects that have recently been reported over the long term in man 3, 4…”