New Drug-Eluting Stents

Abstract

D rug-eluting stents (DES)were primarily conceived to reduce in-stent neointimal formation and therefore minimize the occurrence of restenosis, the major drawback of percutaneous coronary interventions with bare-metal stents (BMS).The development of DES has been pioneered through a combination of the increased understanding of the biology of restenosis, the selection of drugs that target 1 or more pathways in the restenotic process, controlled-release drug delivery strategies, and the use of the stent as a delivery platform.Although first-generation DES Cypher (sirolimus-eluting stent; Cordis Corporation, Johnson & Johnson, Warren, NJ) and Taxus (paclitaxel-eluting stent; Boston Scientific Corporation, Natick, Mass) have effectively achieved their main goal, reducing restenosis across virtually all lesion and patient subsets, their safety has been limited by suboptimal polymer biocompatibility, delayed stent endothelialization leading to late and very late thrombosis, and local drug toxicity. [1][2][3][4][5][6][7][8][9] Both Cypher and Taxus use durable thick polymers to carry and control the release of their antiproliferative agents. The permanent presence of these polymers has been correlated to inflammatory responses and local toxicity in preclinical analysis. 10 -13 Furthermore, durable polymers used in first-generation DES have been associated with mechanical complications (eg, polymer delamination and "webbed" polymer surface leading to stent expansion issues) 14 and nonuniform coating resulting in erratic drug distribution. As a consequence, in recent years, the focus of clinical research has been on the development of novel drug carrier systems including absorbable (or biodegradable) polymers and nonpolymeric stent surfaces. Additional improvements include the development of more modern platforms (eg, better deliverability, radiopacity, flexibility, and radial strength) as well as the use of novel antiproliferative agents or reduced doses of current approved antiproliferative drugs.This review focuses on describing next-generation drugeluting stent systems based on the use of novel coatings and carrier systems developed to enhance DES safety. Initially, we will address the issue of how to plan and conduct first-in-man studies to evaluate efficacy of novel devices for coronary intervention. After this brief introduction, we will discuss the next-generation DES systems and for didactic purpose the text will be divided into 2 parts, focusing on programs with biodegradable polymers and finally moving to nonpolymeric DES. First-in-Man StudiesA lot has changed since our institution conducted the firstever successful in-human DES evaluation, the CypherSirolimus-eluting stent first-in-man (FIM) trial. At that time, 10 years ago, with 15 patients receiving the slow-release formulation and 15 patients receiving the moderate-release version, we were able to show the impressive power of the novel technology in reducing neointimal proliferation by means of surrogate end points: in-stent late luminal loss and intravas...

Thrombotic responses to coronary stents, bioresorbable scaffolds and the Kounis hypersensitivity-associated acute thrombotic syndrome

“…The released drugs have antiproliferative properties and include the sirolimus substance that inhibits the mammalian target of rapamycin and prevents reendothelialization and the antineoplastic agent paclitaxel, thus avoiding stent restenosis (6). The durable polymers used in first generation drug eluting stents have been associated with mechanical complications such as polymer delamination and "webbed" polymer surface leading to stent expansion issues and non-uniform coating resulting in erratic drug distribution (7). The sirolimus and paclitaxel eluting stents, have been approved in the United States in 2003 and 2004 respectively, but are no longer available in the United States and Europe due to superiority of second generation stents.…”

Current status of research and application in vascular stents

“…BioFreedom TM is manufactured into micro-structures on the abluminal surface. This polymer-free local drug delivery system not only avoids the adverse effects of degradation products and non-reacted monomer compounds but also improves healing and integrity of stents [41]. Another commercial stent, Yukon TM (Translumina, Hechingen, Germany) applies the similar drug loading strategy.…”

Current status and future prospects of drug eluting stents for restenosis / Sadašnjost i budućnost stentova za restenozu koji otpuštaju lijekove

“…The OPTIMA (Carbostent and Implantable Devices [CID] S.r.l., Italy) key features are the absence of any polymer to carry the tacrolimus (the proprietary drug-release system with reservoirs on the outer surface of the stent), ensuring the drug release being only tar- geted toward the vessel wall. Integral Carbofilm coating favors early endothelialization of the stent thus reducing the risk of stent thrombosis (42).…”