Safety and efficacy of a novel abluminal groove-filled biodegradable polymer sirolimus-eluting stent

Abstract

Late stent thrombosis (LST) following drug-eluting stent (DES) implantation in patients with coronary artery disease (CAD) is often associated with delayed vascular healing, resulting from vascular inflammation and hypersensitivity to durable polymers and drugs. Therefore, DES design, materials, and coatings have been technologically revolutionized. Herein, we designed a novel abluminal groove-filled biodegradable polymer sirolimus-eluting stent (AGF-BP-SES), with a sirolimus content of only about one-third of traditional DES. The mechanical performances of AGF-BP-SES during compression and expansion were investigated. The pharmacokinetic (PK) profile of sirolimus was studied in the swine model. The in vivo efficacy of AGF-BP-SES was compared with that of Xience PRIME stent. The results showed that AGF-BP-SES exhibited mechanical properties similar to traditional DES, including the rebound ratio of radial contraction/direction, rebound ratio of axial contraction/direction, and inhomogeneity of compression/expansion. Despite utilizing a reduced dose of sirolimus, AGF-BP-SES delivered sirolimus to the coronary artery in a controlled and efficient manner. The stent maintained a safe and effective local drug concentration without local or systemic risks. In the swine model, histopathological indicators predicted safety and biocompatibility of AGF-BP-SES. In conclusion, AGF-BP-SES maintained similar mechanical properties as other stents while reducing the drug-loading capacity, and showed a favorable safety and efficacy profile of the targeted DES.

Safety of drug-eluting stents for stenting patent arterial duct in neonates

“…Prior studies have demonstrated delivery of sirolimus to the coronary artery in a controlled way with abluminal drug delivery. 10,11 The stent preserved a safe and effective local drug concentration without significant toxicity. Sirolimus-eluting stents have been used for reopening occluded Blalock-Taussig shunts in infants.…”

The Firehawk stent: a review of a novel abluminal groove-filled biodegradable polymer sirolimus-eluting stent

“…In a subgroup analysis, there were no signifi cant between-group diff erences with respect to prespecifi ed clinical and lesion characteristics. 10 Th e TAR-GET All-Comers study clearly demonstrated that the Firehawk stent is non-inferior to the benchmark XIENCE stent as assessed with the primary endpoint of TLF at 12 months in an all-comers population. Furthermore, the results confi rmed the clinical evaluations performed in China, and represent a successful global approval pathway for a Chinese DES in Europe.…”

“…Th e Firehawk stent is designed to minimize polymer burden and reduce drug concentrations in the vessel wall. In fact, it represents the lowest polymer volume and drug concentration among currently available biodegradable polymer DES 10 . In a porcine model, the use of abluminal grooves allowed an equivalent concentration of sirolimus to be delivered to the endothelial tissue while decreasing the amount of circulating drug by nearly 7-fold when compared to the conventional Cypher sirolimus-eluting stent (Johnson & Johnson, New Brunswick, USA) (113 pg/ml vs. 733 pg/ml) 11 .…”

“…Th e primary endpoint of the study was TLF at 12 months,which was low (4.4%) with only one defi nite or probable stent thrombosis reported. When the participants were divided into three groups according to coronary lesion complexity, patients 10 . From December 2015 to October 2016, 1653 patients from 21 medical centers in 10 European countries were enrolled and 823 were randomized to treatment with the Firehawk stent.…”