Polymer-Free Biolimus A9-Coated Stent Demonstrates More Sustained Intimal Inhibition, Improved Healing, and Reduced Inflammation Compared With a Polymer-Coated Sirolimus-Eluting Cypher Stent in a Porcine Model

Tada, Norio; Virmani, Renu; Grant, Gordon W.; Bartlett, Lauren; Black, Alexander; Clavijo, Claudia F.; Christians, Uwe; Betts, Ron; Savage, Doug; Su, Solomon; Shulze, John; Kar, Saibal

doi:10.1161/circinterventions.109.877522

Cited by 132 publications

(57 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

View full text Add to dashboard Cite

SummaryBackground Data for the safety and effi cacy of new-generation drug-eluting stents at long-term follow-up, and specifi cally in patients with ST-segment elevation myocardial infarction, are scarce. In the EXAMINATION trial, we compared everolimus-eluting stents (EES) with bare-metal stents (BMS) in an all-comer population with ST-segment elevation myocardial infarction. In this study, we assessed the 5-year outcomes of the population in the EXAMINATION trial.

show abstract

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

View full text Add to dashboard Cite

show abstract

“…In a preclinical study, the umirolimus-coated stent showed less neointimal proliferation and inflammation at 180 days than did a sirolimus-eluting stent. 6 In a first-in-human evaluation, the umirolimus-coated stent was noninferior to a paclitaxel-eluting stent with respect to in-stent late lumen loss at 12 months. 7 The Prospective Randomized Comparison of the BioFreedom Biolimus A9 Drug-Coated Stent versus the Gazelle Bare-Metal Stent in Patients at High Bleeding Risk (LEADERS FREE) trial was designed to evaluate the efficacy and safety of the polymer-free umirolimus-coated stent as compared with a bare-metal stent in patients with increased bleeding risk, with a 1-month regimen of dual antiplatelet therapy in both groups.…”

mentioning

confidence: 98%

Polymer-free Drug-Coated Coronary Stents in Patients at High Bleeding Risk

et al. 2015

View full text Add to dashboard Cite

BACKGROUND: Patients at high risk for bleeding who undergo percutaneous coronary intervention (PCI) often receive bare-metal stents followed by 1 month of dual antiplatelet therapy. We studied a polymer-free and carrier-free drug-coated stent that transfers umirolimus (also known as biolimus A9), a highly lipophilic sirolimus analogue, into the vessel wall over a period of 1 month. METHODS: In a randomized, double-blind trial, we compared the drug-coated stent with a very similar bare-metal stent in patients with a high risk of bleeding who underwent PCI. All patients received 1 month of dual antiplatelet therapy. The primary safety end point, tested for both noninferiority and superiority, was a composite of cardiac death, myocardial infarction, or stent thrombosis. The primary efficacy end point was clinically driven target-lesion revascularization. RESULTS: We enrolled 2466 patients. At 390 days, the primary safety end point had occurred in 112 patients (9.4%) in the drug-coated-stent group and in 154 patients (12.9%) in the bare-metal-stent group (risk difference, -3.6 percentage points; 95% confidence interval [CI], -6.1 to -1.0; hazard ratio, 0.71; 95% CI, 0.56 to 0.91; P<0.001 for noninferiority and P=0.005 for superiority). During the same time period, clinically driven target-lesion revascularization was needed in 59 patients (5.1%) in the drug-coated-stent group and in 113 patients (9.8%) in the baremetal-stent group (risk difference, -4.8 percentage points; 95% CI, -6.9 to -2.6; hazard ratio, 0.50; 95% CI, 0.37 to 0.69; P<0.001). CONCLUSIONS: Among patients at high risk for bleeding who underwent PCI, a polymer-free umirolimus-coated stent was superior to a bare-metal stent with respect to the primary safety and efficacy end points when used with a 1-month course of dual antiplatelet therapy. (Funded by Biosensors Europe; LEADERS FREE ClinicalTrials.gov number, NCT01623180.).

show abstract

“…However, stent implantation, including BMS and polymer-coated DES implantation, induces acute and chronic inflammation that stimulates accumulation of inflammatory cells, such as macrophages and T-lymphocytes, and inflammatory cytokine secretion (8). Inhibition of inflammatory gene expression may have the therapeutic effect of reducing neointimal hyperplasia.…”

Section: Anti-inflammationmentioning

confidence: 99%

“…In addition, antiproliferative drugs in DES, primarily aimed at preventing VSMC proliferation (which is central to the pathogenesis of ISR), also perturb endothelial recovery (6), which consequently increases the risk for subacute in-stent thrombosis and results in late stent thrombosis (ST) (7). Furthermore, polymer coatings on DES induce a distinct inflammatory reaction compared with bare metal surfaces (8). These results raise serious questions regarding the long-term durability and efficacy of DES, thereby resulting in an urgent need to develop new therapies to prevent restenosis.…”

mentioning

confidence: 99%

Gene therapy for in-stent restenosis: Targets and delivery system

Yin¹,

Agrawal²

2014

Curr Res Cardiol

View full text Add to dashboard Cite

Despite the increased use of drug-eluting stents (DES), the incidence of in-stent restenosis (ISR) requiring target vessel revascularization remains unacceptably high (1,2). The incidence rate of ISR requiring target vessel revascularization (ie, 'DES failure') in the United States alone was conservatively estimated to be 10%, and may be more common in patients with diabetes mellitus (3). Although the pathophysiology of DES failure is complex, histopathological changes of in-stent neointima following directional atherectomy at the time of reintervention have been shown to be remarkably similar between bare-metal stents (BMS) and DES, suggesting that a process mediated by the endothelial injury, inflammation, proliferation and migration of vascular smooth muscle cells (VSMCs), and thrombosis plays the same important role in the progress of ISR of DES (4,5). In addition, antiproliferative drugs in DES, primarily aimed at preventing VSMC proliferation (which is central to the pathogenesis of ISR), also perturb endothelial recovery (6), which consequently increases the risk for subacute in-stent thrombosis and results in late stent thrombosis (ST) (7). Furthermore, polymer coatings on DES induce a distinct inflammatory reaction compared with bare metal surfaces (8). These results raise serious questions regarding the long-term durability and efficacy of DES, thereby resulting in an urgent need to develop new therapies to prevent restenosis. The present review focuses on the progress made to date in the use of gene therapy, including catheter-based gene delivery and gene-eluting stents (GES), to prevent ISR. We will also discuss the current and promising application of magnetic targeting gene delivery systems for antirestenosis therapy. Evolution of antirEstEnosis thErapyIn the past several decades, percutaneous transluminal coronary angioplasties have revolutionized the treatment of atherosclerosis-related cardiovascular disease. At the same time, tremendous efforts have also been made to reduce the incidence of restenosis after percutaneous transluminal coronary angioplasties (9). During the time in which 'plain old balloon angioplasty' was prevalent, rates of acute and chronic vessel occlusion were higher (30% to 56%), secondary to acute/chronic recoil and constrictive remodelling (10). These problems led to the development of a second revolutionary treatment, BMS, which were first implanted in 1986 (11). Although this 'bailout' scaffold significantly reduced the issue of acute and chronic recoil, its application was ultimately hampered by the risk for subacute thrombotic coronary artery occlusion and neointimal hyperplasia (12). The restenosis rates with BMS were reported to be between 16% and 44%, with higher rates of stenosis attributable to several risk factors, particularly long lesion length and small vessel calibre (1,13). Considerable progress to reduce the incidence of restenosis was made by the advent of DES, which are composed of a metallic stent, a polymer-based drug delivery platform and a pharmacolog...

show abstract

Polymer-Free Biolimus A9-Coated Stent Demonstrates More Sustained Intimal Inhibition, Improved Healing, and Reduced Inflammation Compared With a Polymer-Coated Sirolimus-Eluting Cypher Stent in a Porcine Model

Abstract: Background-Drug-eluting stents effectively reduce restenosis but may increase late thrombosis and delayed restenosis.Persistent polymer, the drug, or a combination of both could be responsible.

Cited by 132 publications

References 34 publications

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

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

Polymer-free Drug-Coated Coronary Stents in Patients at High Bleeding Risk

Gene therapy for in-stent restenosis: Targets and delivery system

Contact Info

Product

Resources

About