Seguridad y eficacia de nuevos modelos de stents liberadores de sirolimus con polímero biodegradable en el modelo preclínico / Safety and efficacy of new biodegradable polymer-based sirolimus-eluting stents in a preclinical model

Introducción y objetivos: Los nuevos stents farmacoactivos (SFA), diseñados para solventar las limitaciones de los existentes, han de someterse inicialmente al análisis preclínico. El objetivo es analizar la eficacia y la seguridad de nuevos SFA con polímero biodegradable en comparación con stents convencionales (SC) y SFA comercializados en el modelo de arteria coronaria sana porcina. Métodos: Se implantaron aleatoriamente 101 stents (SC y stents liberadores de sirolimus con polímero biodegradable: 3 formulaciones test [BD1, BD2 y BD3], Orsiro, Biomime y Biomatrix) en las arterias coronarias de 34 cerdos domésticos. Se completó estudio angiográfico e histomorfométrico al mes (n = 83) y a los 3 meses (n = 18). Resultados: Los stents se implantaron en proporción stent/arteria de 1,31 ± 0,21, sin diferencias entre grupos. Al mes, los nuevos stents (BD1, BD2 y BD3) mostraron menos pérdida tardía y reestenosis angiográfica, así como menor área neointimal y reestenosis histológica (p < 0,0005) que los SC. No se observaron diferencias significativas entre los nuevos stents y los SC en endotelización, daño vascular o inflamación; solo se encontró mayor persistencia de fibrina en los nuevos (p = 0,0006). A los 3 meses, todas estas diferencias desaparecieron, excepto una menor área neointimal con el nuevo stent BD1 (p = 0,027). No hubo diferencias en ningún parámetro al mes ni a los 3 meses entre los nuevos stents y los comercializados. Conclusiones: En este modelo preclínico, los nuevos SFA con polímero biodegradable estudiados presentan menos reestenosis que los SC, sin diferencias significativas en seguridad y eficacia respecto a SFA comercializados (AU)

Introduction and objectives New drug-eluting stents (DES) designed to overcome the limitations of existing devices should initially be tested in preclinical studies. Our objective was to analyze the safety and efficacy of new biodegradable polymer-based DES compared with bare-metal stents (BMS) and commercially available DES in a model of normal porcine coronary arteries. Methods: We randomly implanted 101 stents (BMS and biodegradable polymer-based sirolimus-eluting stents: 3 test stent iterations [BD1, BD2, and BD3], Orsiro, Biomime and Biomatrix) in the coronary arteries of 34 domestic pigs. Angiographic and histomorphometric studies were conducted 1 month (n = 83) and 3 months (n = 18) later. Results: The stents were implanted at a stent/artery ratio of 1.31 ± 0.21, with no significant differences between groups. At 1 month, the new test stents (BD1, BD2 and BD3) showed less late loss and angiographic restenosis, as well as lower histologic restenosis and neointimal area (P < .0005), than the BMS. There were no differences in endothelialization, vascular injury, or inflammation between the new test stents and BMS, although the new stents showed higher fibrin deposition (P = .0006). At 3 months, all these differences disappeared, except for a lower neointimal area with the new BD1 stent (P = .027). No differences at any time point were observed between the new test stents and commercially available controls. Conclusions: In this preclinical model, the new biodegradable polymer-based DES studied showed less restenosis than BMS and no significant differences in safety or efficacy vs commercially available DES (AU)

Safety and Efficacy of New Biodegradable Polymer-based Sirolimus-Eluting Stents in a Preclinical Model.

INTRODUCTION AND OBJECTIVES: New drug-eluting stents (DES) designed to overcome the limitations of existing devices should initially be tested in preclinical studies. Our objective was to analyze the safety and efficacy of new biodegradable polymer-based DES compared with bare-metal stents (BMS) and commercially available DES in a model of normal porcine coronary arteries. METHODS: We randomly implanted 101 stents (BMS and biodegradable polymer-based sirolimus-eluting stents: 3 test stent iterations [BD1, BD2, and BD3], Orsiro, Biomime and Biomatrix) in the coronary arteries of 34 domestic pigs. Angiographic and histomorphometric studies were conducted 1 month (n = 83) and 3 months (n = 18) later. RESULTS: The stents were implanted at a stent/artery ratio of 1.31 ± 0.21, with no significant differences between groups. At 1 month, the new test stents (BD1, BD2 and BD3) showed less late loss and angiographic restenosis, as well as lower histologic restenosis and neointimal area (P < .0005), than the BMS. There were no differences in endothelialization, vascular injury, or inflammation between the new test stents and BMS, although the new stents showed higher fibrin deposition (P = .0006). At 3 months, all these differences disappeared, except for a lower neointimal area with the new BD1 stent (P = .027). No differences at any time point were observed between the new test stents and commercially available controls. CONCLUSIONS: In this preclinical model, the new biodegradable polymer-based DES studied showed less restenosis than BMS and no significant differences in safety or efficacy vs commercially available DES.