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.

BACKGROUND:Drug-eluting stents (DES) are widely used for treatment of coronary artery disease with benefit of reduced restenosis compared to bare metal stents. The XIENCE VEverolimus Eluting Coronary Stent System is a second-generation DES system for better deliverability while maintaining safety and efficacy profiles. The present pharmacokinetic sub-study from the SPIRIT III Randomized and Controlled Trial (RCT) was to evaluate systemic exposure of patients to everolimus and to further demonstrate safety following implantation of XIENCE Vstents with everolimus doses ranging from 53 to 181 microg.METHODS AND RESULTS:Drug concentrations in whole blood were determined at multiple time points using a validated analytical method with a limit of quantification of 0.1 ng/mL. Individual C(max) ranged from 0.17 to 2.40 ng/mL and occurred between 0.07 and 1.88 hours across all dose levels. Both mean and individual C(max) values were below the trough blood concentrations of everolimus (Certican) for inhibition of organ transplant rejection. The last time point at which drug concentrations could be quantified ranged from 12 to 168 hours postimplantation in individual patients. In most cases, the blood levels dropped below the limit of quantification after 72 hours.CONCLUSIONS:This study confirms that the XIENCE Vstent causes a limited and systemic exposure to everolimus. The presumed localized and efficient delivery of everolimus to target vessels coupled with limited and transient systemic drug exposure contributes to the safety and effectiveness of the XIENCE VEECSS in patients of SPIRIT III RCT for longer than 2 years.

Background: The XIENCE V™ everolimus‐eluting coronary stent system is a second‐generation drug‐eluting stent designed for safety and efficacy in the interventional treatment of coronary artery disease and in preventing in‐stent restenosis. A comprehensive preclinical program was completed to aid in the scientific design and to demonstrate the safety of XIENCE V. Methods: Studies evaluating clinical dose selection, pharmacokinetics, single and overlapping stent safety, polymer safety, and maximum dose (8× everolimus) safety were conducted in the porcine coronary arterial model at 28, 90, 180 days, and 1 and 2 years. Additionally, a subset of studies was conducted in the rabbit iliac arterial model. Results: Morbidity and mortality rates for all preclinical studies were exceptionally low, being less than 1%. The arterial response observed in the clinical dose selection study and in all safety studies was typified by benign neointimal hyperplasia with endothelialization by 28 days. Everolimus was released in a controlled manner for 120 days and remained primarily localized within the stented arterial region, which was evidenced histologically as peristrut fibrin. The temporal presence of peristrut fibrin matched the everolimus‐elution profile. Thrombosis, malapposition, medial loss, or other adverse effects were not observed in any preclinical studies. Conclusion: XIENCE V has demonstrated safety via an extremely comprehensive preclinical program published to date for a DES system, with data generated in two species to 2 years. The preclinical data, along with the SPIRIT clinical trial data, demonstrate the excellent safety and potential efficacy profile of XIENCE V.