Short- and mid-term intravascular ultrasound analysis of the new zotarolimus-eluting stent with durable polymer ­ results from the RESOLUTE trial ­.

BACKGROUND: The Resolute stent is a newly developed system with a bio-histocompatible polymer that allows programmed drug delivery up to 180 days. The aim of this intravascular ultrasound (IVUS) analysis was to evaluate the short- (4 months) and mid-term (9 months) efficacy using the Resolute stent. METHODS AND RESULTS: Data were derived from the RESOLUTE trial, a prospective, multicenter, non-randomized, single-arm study to treat de novo native coronary artery lesions. This trial included 2 cohorts with different follow-up periods, and all enrollment patients in this trial received IVUS study. Follow-up IVUS was available in 24 patients (4-month group) and 88 patients (9-month group). Neointimal obstruction (%) was defined as neointimal volume divided by stent volume. Cross-sectional narrowing (CSN, %) was defined as neointimal area divided by stent area. No significant differences in vessel, lumen and stent volume at post-procedure were observed within stented segments between the 4- and 9-month follow-up groups. Although neointimal volume and % neointimal obstruction showed no significant difference between the 2 groups (% neointimal obstruction: 2.2 ± 2.5 vs 3.7 ± 4.0%, P=0.09), maximum CSN was significantly larger in the 9-month group. There were 7 cases of late incomplete stent apposition. CONCLUSIONS: These IVUS results showed minimum growth of neointimal proliferation by the Resolute stent throughout the stented segment up to 9 months follow up.

Self-Expanding Transcatheter Aortic Valve System for Symptomatic High-Risk Patients With Severe Aortic Stenosis.

BACKGROUND: The CENTERA transcatheter heart valve (THV) is a low-profile, self-expanding nitinol valve made from bovine pericardial tissue that is 14-F compatible with a motorized delivery system allowing for repositionability. OBJECTIVES: The pivotal study evaluated safety and efficacy of this THV in high-surgical-risk study patients with severe symptomatic aortic stenosis. METHODS: Implantations were completed in 23 centers. Clinical and echocardiographic outcomes were assessed at baseline, discharge, and 30 days. Major events were adjudicated by an independent clinical events committee. Echocardiograms and computed tomography scans were reviewed by core laboratories. The primary endpoint was all-cause mortality at 30 days. RESULTS: Between March 25, 2015 and July 5, 2016, 203 patients with severe symptomatic aortic stenosis and increased surgical risk, as determined by the heart team, were treated by transfemoral THV implantation (age 82.7 ± 5.5 years, 67.5% female, 68.0% New York Heart Association functional class III/IV). At 30 days, mortality was 1%, disabling stroke occurred in 2.5% of patients, and New York Heart Association functional class I/II was observed in 93.0% of patients. Effective orifice area increased from 0.71 ± 0.20 cm2 to 1.88 ± 0.43 cm2 (p < 0.001). Mean aortic transvalvular gradient decreased from 40.5 ± 13.2 mm Hg to 7.2 ± 2.8 mm Hg at 30 days post-procedure (p < 0.001). Paravalvular aortic regurgitation at 30 days was moderate or higher in 0.6% of patients. A new permanent pacemaker was implanted in 4.5% of patients receiving the THV (4.9% for patients at risk). CONCLUSIONS: The herein described THV is safe and effective at 30 days with low mortality, significant improvements in hemodynamic outcomes, and low incidence of adverse events. Of particular interest is the low incidence of permanent pacemaker implantations. (Safety and Performance Study of the Edwards CENTERA-EU Self-Expanding Transcatheter Heart Valve [CENTERA-2]; NCT02458560).

Paclitaxel-eluting balloon and everolimus-eluting stent for provisional stenting of coronary bifurcations: 12-month results of the multicenter BIOLUX-I study.

BACKGROUND: Several studies investigated the combination of bare metal stents in the main branch and drug-eluting balloons in the side branch in bifurcation lesions, but data on the combination of drug-eluting stents and drug-eluting balloons are scarce. We aim to assess the feasibility of provisional stenting with an everolimus-eluting stent in the main branch and a paclitaxel-eluting balloon in the side branch. METHODS: In this prospective, multi-center study conducted in 5 Australian sites, 35 patients with bifurcation lesions were enrolled. Angiographic and intravascular ultrasound assessments were conducted at 9 months; clinical follow-up was conducted until 12 months. RESULTS: The primary endpoint, late lumen loss in the side branch measured by quantitative coronary angiography, was 0.10±0.43mm. No binary restenosis was observed. One patient died; 3 myocardial infarctions (one suspected and two in non-target vessels) and one target lesion revascularization occurred. No probable or definite stent thrombosis was observed. CONCLUSION: The combination of an everolimus-eluting stent in the main branch and a paclitaxel-eluting balloon in the side branch appears to be a safe, effective and novel treatment option for bifurcation lesions.

Six-month IVUS and two-year clinical outcomes in the EVOLVE FHU trial: a randomised evaluation of a novel bioabsorbable polymer-coated, everolimus-eluting stent.

AIMS: The EVOLVE FHU trial demonstrated non-inferiority of six-month late loss with two dose formulations of SYNERGY, a novel bioabsorbable polymer everolimus-eluting stent (EES) compared with the durable polymer PROMUS Element (PE) EES. The current analysis describes the six-month IVUS and clinical results through two years from the EVOLVE FHU trial. METHODS AND RESULTS: EVOLVE recruited 291 patients from 29 centres. At six months, IVUS-assessed in-stent net volume obstruction was 3.40 ± 5.06% for PROMUS Element (PE) vs. 2.68 ± 4.60% for SYNERGY (p=0.34) and 3.09 ± 4.29% for SYNERGY ½ dose (p=0.68 vs. PE). There were no significant differences between groups for any other measured IVUS parameter including resolved, persistent, and late-acquired incomplete stent apposition (ISA). At two years, target lesion failure (TLF) was 6.1% for PE vs. 5.5% for SYNERGY (p=0.87) and 5.2% for SYNERGY ½ dose (p=0.81). There were no significant differences between groups for cardiac death, repeat revascularisation, MI or stent thrombosis through two years. CONCLUSIONS: At six months, everolimus delivered from an ultrathin bioabsorbable abluminal polymer resulted in equivalent net volume obstruction and ISA compared with a permanent polymer EES. There were no significant differences between PE and either SYNERGY stent for any major cardiac endpoint through two years. Clinical trials number: NCT01135225.

Impact of polymer formulations on neointimal proliferation after zotarolimus-eluting stent with different polymers: insights from the RESOLUTE trial.

BACKGROUND: Polymer formulation may affect the efficacy of drug-eluting stents. Resolute, Endeavor, and ZoMaxx are zotarolimus-eluting stents with different stent platforms and different polymer coatings and have been tested in clinical trials. The aim of this analysis was to compare the efficacy of zotarolimus-eluting stents with different polymers. METHODS AND RESULTS: Data were obtained from the first-in man trial or first randomized trials of each stent, The Clinical RESpOnse EvaLUation of the MedTronic Endeavor CR ABT-578 Eluting Coronary Stent System in De Novo Native Coronary Artery Lesions (RESOLUTE), Randomized Controlled Trial to Evaluate the Safety and Efficacy of the Medtronic AVE ABT-578 Eluting Driver Coronary Stent in De Novo Native Coronary Artery Lesions (ENDEAVOR II), and ZoMaxx I trials. Follow-up intravascular ultrasound analyses (8 to 9 months of follow-up) were possible in 353 patients (Resolute: 88, Endeavor: 98, ZoMaxx: 82, Driver: 85). Volume index (volume/stent length) was obtained for vessel, stent, lumen, peristent plaque, and neointima. Cross-sectional narrowing was defined as neointimal area divided by stent area (%). Neointima-free frame ratio was calculated as the number of frames without intravascular ultrasound-detectable neointima divided by the total number of frames within the stent. At baseline, vessel, lumen, and peristent plaque volume index were not significantly different among the 4 stent groups. At follow-up, percent neointimal obstruction was significantly lower in Resolute compared with Endeavor, ZoMaxx, and Driver (Resolute: 3.7±4.0, Endeavor: 17.5±10.1, ZoMaxx: 14.6±8.1, Driver: 29.4±17.2%; P<0.001). Greater maximum cross-sectional narrowing and higher neointima-free frame ratio, suggesting less neointimal coverage, were observed in Resolute compared with other stent groups. Multiple regression analysis confirmed that the biodurable polymer used in Resolute independently correlated with neointimal suppression among 3 zotarolimus-eluting stents. CONCLUSIONS: The different polymer formulations significantly affect the relative amount of neointima for zotarolimus-eluting stents. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00248079.

Long-term clinical outcomes with the next-generation Resolute Stent System: a report of the two-year follow-up from the RESOLUTE clinical trial.

AIMS: The 12-month results of RESOLUTE were favourable for the new Resolute stent. Two-year safety and efficacy results from RESOLUTE have been evaluated and are now reported. METHODS AND RESULTS: RESOLUTE was a prospective, multicentre, non-randomised, single-arm, controlled trial of the Resolute stent in 139 participants with symptomatic ischaemic heart disease due to single de novo lesions in a native coronary artery. The 2-year rates of MACE (all-cause death, myocardial infarction, emergent cardiac bypass surgery, and target lesion revascularisation [TLR]), death, late stent thrombosis, target vessel revascularisation (TVR), and target vessel failure (TVF) were assessed. Clinical events included two MACE (one TLR; one non-cardiac death) occurring between year one and two resulting in cumulative 2-year TLR, TVR, and TVF rates of 1.4%, 1.4%, and 7.9%, respectively. One possible stent thrombosis event occurred in the first year after stent implantation however no late or very late ARC-defined definite and probable stent thromboses occurred through two years. CONCLUSIONS: The 2-year data from RESOLUTE demonstrated no safety concerns including no late stent thrombosis or loss of effectiveness with the Resolute stent. The finding that few events occurred in year two is encouraging, yet requires verification in a larger population.

Deciphering dual antiplatelet therapy in the era of drug-eluting coronary stents.

The recently described complication of late and very late stent thrombosis with coronary stents has raised the question of when is it safe to stop antiplatelet therapy in the era of drug eluting stents? With several million patients having already had coronary stents implanted worldwide, the importance of an appreciation of stent thrombosis is not only critical to the cardiologist but also surgeon, physician, dentist and other specialists that perform procedures on patients which require with-holding antiplatelet agents. Currently there is great concern amongst medical professionals on how to manage this group of patients in the absence of clear guidelines. This article reviews the current data on coronary stents, in-stent restenosis and stent thrombosis and role of antiplatelet medication post percutaneous coronary intervention (PCI) to provide a concise and clear algorithm for managing perioperative antiplatelet therapy in patients having undergone recent PCI. The algorithm encourages a multidisciplinary approach and is based on the surgical bleeding risk, operative risk of adverse cardiac events and stent thrombosis risk to guide safe practice. Challenging areas including aspirin and clopidogrel hypersensitivity, clopidogrel resistance and concomitant vitamin K antagonist therapy are also addressed.