Comparison of vascular response between durable and biodegradable polymer-based drug-eluting stents in a porcine coronary artery model

Abstract

Biodegradable polymer-based drug-eluting stents are thought to be safer than durable polymer-based stents. However, the long-term vascular response remains unclear. The aim of this study was to compare the biocompatibility of durable polymer-based sirolimus-eluting (SES) and everolimus-eluting (EES) stents with biodegradable polymer-based biolimus-eluting (BES) stents in a porcine coronary model. Stents were implanted in porcine coronaries. Acetylcholine challenge tests and optical coherence tomography (OCT) examination were performed at one month. Animals were sacrificed at three and six months (n=6 each), and the stents were analysed histologically. At one month, acetylcholine challenge tests revealed a trend towards greatest vasoconstriction in SES, less in BES, and least in EES, but the differences were not significant. OCT analysis demonstrated the highest incidence of uncovered struts in SES, followed by BES, while EES showed almost complete strut coverage (41.7±27.0%, 24.5±23.8%, 0.4±0.8%, respectively; p=0.004). Upon histological analysis at three months, SES showed a significantly higher inflammatory score than BES and EES (2.9±1.4, 0.8±0.9, 0.5±0.4, respectively; p=0.001), and this was maintained at six months (1.6±1.5, 0.3±0.3, 0.4±0.6, respectively; p=0.049). While SES showed an increased inflammatory reaction, EES and BES showed minimal inflammation. These results indicate that the late inflammatory reaction does not necessarily depend on degradability of the polymer, if the combination of the drug, metal, and polymer is biocompatible.

A comparison of drug eluting stent biocompatibility between third generation NOBORI biolimus A9-eluting stent and second generation XIENCE V everolimus-eluting stent in a porcine coronary artery model

“…Similar with recent clinical trials, most of previous preclinical studies comparing BES and EES have failed to show the differences between the biodegradable polymer stents and the durable polymer stents [11,12]. Nakazawa reported that BES and EES showed similar biocompatibility while sirolimus-eluting stents (SES) showed severe inflammatory reactions in porcine coronary arteries [11].…”

“…We speculate that the most critical component of DES is the stent polymer, neither the antiproliferative agent nor the stent platform. Our stent length (23-or 24-mm lengths) is longer than conventional stent length (18-mm) used in the majority of previous studies [11,12,13]. Longer stents are loaded with more polymers, resulting in these remarkable differences between BES and EES in terms of inflammation and immunoreaction.…”

“…Nakazawa reported that BES and EES showed similar biocompatibility while sirolimus-eluting stents (SES) showed severe inflammatory reactions in porcine coronary arteries [11]. Also, Hiranuma showed no significant differences between BES and EES by optical coherence tomography at one month after stent implantation [12].…”

Clinical outcomes in patients with ST-segment elevation myocardial infarction treated with everolimus-eluting stents versus bare-metal stents (EXAMINATION): 5-year results of a randomised trial

“…12 Therefore, research in this fi eld has been redirected toward biodegradable polymer-based metallic DES, polymer-free DES, or completely bioresorbable scaff olds. [28][29][30] Although these pathological fi ndings were noted after implantation of fi rst-generation DES, the use of EES has provided reassuring data in imaging studies in animals and people [31][32][33] that have been confi rmed in a network meta-analysis of ST-elevation myocardial infarction. 34 However, this meta-analysis was limited by the availability of only two trials specifi cally designed for patients with ST-elevation myocardial infarction (the EXAMINATION trial 21 and the XAMI trial 35 of the comparison of EES vs fi rst-generation sirolimus-eluting stents) and by the shorter follow-up (1 year and 2 years).…”

Five-Year Optical Coherence Tomography in Patients With ST-Segment–Elevation Myocardial Infarction Treated With Bare-Metal Versus Everolimus-Eluting Stents

“…It has been shown that the acrylic and fluoro permanent polymers of the EES cause less inflammatory reaction to the vessel wall than other polymers. 20 The everolimus drug is completely eluted 4 months after stent implantation. Then, the stent behaves as a metallic stent but coated with the permanent polymer.…”