117 research outputs found
Single and combined effects of αvÎČ3- and α5ÎČ1-integrins on capillary tube formation in a human fibrinous matrix
The fibrinous exudate of a wound or tumor stroma facilitates angiogenesis. We studied the involvement of RGD-binding integrins during tube formation in human plasma-derived fibrin clots and human purified fibrin matrices. Capillary-like tube formation by human microvascular endothelial cells in a 3D plasma-derived fibrinous matrix was induced by FGF-2 and TNF-α and depended largely on cell-bound u-PA and plasmin activities. While tube formation was minimally affected by the addition of either the αvÎČ3-integrin inhibiting mAb LM609 or the α5-integrin inhibiting mAb IIA1, the general RGD-antagonist echistatin completely inhibited this process. Remarkably, when αvÎČ3- and α5ÎČ1-integrins were inhibited simultaneously, tube formation was reduced by 78%. It was accompanied by a 44% reduction of u-PA antigen accumulation and 41% less production of fibrin degradation products. αvÎČ5-integrin-blocking antibodies further enhanced the inhibition by mAb LM609 and mAb IIA1 to 94%, but had no effect by themselves. αv-specific cRGD only inhibited angiogenesis when α5ÎČ1-integrin was simultaneously blocked. Endostatin mimicked the effect of α5ÎČ1-integrin and inhibited tube formation only in the presence of LM609 or cRGD (73 and 80%, respectively). Comparable results were obtained when purified fibrin matrices were used instead of the plasma-derived fibrinous matrices. These data show that blocking of tube formation in a fibrinous exudate requires the simultaneous inhibition of αvÎČ3- and α5ÎČ1-integrins. This may bear impact on attempts to influence angiogenesis in a fibrinous environment
Role of fibroblasts in the regulation of proinflammatory interleukin IL-1, IL-6 and IL-8 levels induced by keratinocyte-derived IL-1
Safety of second-generation drug-eluting stents three years after randomised use in the TWENTE trial
Aims: To assess three-year clinical outcome following randomised use of the second-generation Resolute zotarolimus-eluting stent (ZES) and the XIENCE V everolimus-eluting stent (EES). For Resolute ZES and randomised use, outcome data â„3 years are relatively scarce. Methods and results: The TWENTE trial examined 1,391 patients with stable angina or non-ST-elevation acute coronary syndromes, of whom 21.6% were diabetics, 70.1% had complex B2 or C lesions and 77.4% had âoff-labelâ indications for DES use. Three-year follow-up data were obtained in 1,381 patients (99.3%; 10 withdrawals). Adverse clinical events were independently adjudicated. The primary endpoint target vessel failure (TVF), a composite of cardiac death, target vessel-related myocardial infarction and clinically indicated target vessel revascularisation, was 12.1% for Resolute ZES and 13.4% for XIENCE V EES (p=0.50). Cardiac death rates were 1.9% vs. 3.5% (p=0.06); the other individual components of TVF also showed no significant between-group differences. The rates of definite-or-probable stent thrombosis (1.4% vs. 1.6%, p=0.82) and very late stent thrombosis (0.6% vs. 0.4%, p=1.0) did not differ between the groups. Conclusions: Three-year follow-up data of patients included in the randomised TWENTE trial demonstrated similar and sustained safety and efficacy of Resolute ZES and XIENCE V EE
Impact of previous coronary artery bypass surgery on clinical outcome after percutaneous interventions with second generation drug-eluting stents in TWENTE trial and Non-Enrolled TWENTE registry
AbstractBackgroundPatients with previous coronary artery bypass grafting (CABG) who underwent percutaneous coronary intervention (PCI) have an increased repeat revascularization rate, but data on contemporary second-generation drug-eluting stents (DES) are scarce.MethodsWe evaluated 1-year clinical outcome following secondary revascularization by PCI in patients of the TWENTE trial and non-enrolled TWENTE registry, and compared patients with previous CABG versus patients without previous CABG.ResultsOf all 1709 consecutive patients, 202 (11.8%) had previously undergone CABG (on average 11.2±8.5years ago). CABG patients were older (68.5±9.4years vs. 64.1±10.7years, P<0.001) and more often had diabetes (28.7% vs. 20.9%, P=0.01) and previous PCI (40.1% vs. 19.8%, P<0.001) compared to patients without previous CABG. Nevertheless, a higher target vessel revascularization (TVR) rate following PCI in the CABG patients (9.4% vs. 2.3%, P<0.001) was the only significant difference in clinical outcome at 1-year follow-up (available for 99.6%). Among CABG patients, the TVR rate was significantly higher in patients treated for graft lesions (n=65; 95.4% in vein grafts) than in patients treated for native coronary lesions only (n=137) (18.5% vs. 5.1%, P=0.002). Among 1638 patients with PCI of native coronary lesions only, there was only a non-significant difference in TVR between patients with previous CABG versus patients without previous CABG (5.1% vs. 2.3%, P=0.08).ConclusionsPatients with previous CABG showed a favorable safety profile after PCI with second-generation DES. Nevertheless, their TVR rate was still much higher, driven by more repeat revascularizations after PCI of degenerated vein grafts. In native coronary lesions, there was no such difference
TCT-342 Risk and Consequences of Periprocedural Myocardial Infarction Following Off-Label Use of Second Generation Drug-Eluting Stents: Two-Year Follow-up in the TWENTE Trial
Patient preference regarding assessment of clinical follow-up after percutaneous coronary intervention: the PAPAYA study
Aims: To keep patients in long-term clinical follow-up programmes after percutaneous coronary intervention (PCI), knowledge of the patient-preferred mode for follow-up assessment is crucial. We systematically assessed patient preference, and explored potential relationships with age and gender.Methods and results: In the prospective, observational PAPAYA study (ClinicalTrials.gov: NCT02189070), 2,566 patients, treated by PCI between June 2008 and May 2012, were invited to participate in a postal survey on the patient-preferred mode (postal questionnaire, telephone or e-mail consultation) and frequency of follow-up assessment. A total of 1,797 (70.0%) patients responded. The vast majority preferred completing postal questionnaires (1,248 [69.9%]) as compared to telephone (240 [13.4%]) or e-mail-based approaches (227 [12.7%]) (p<0.001). With increasing age, there was a gradual decline in preference for e-mail (p<0.001); the youngest patients (â€60 years) preferred e-mail-based follow-up more often than the oldest (21.1% vs. 3.1%). Nevertheless, 79.9% of the youngest preferred to be approached in ways other than by e-mail. Women more often preferred approaches other than e-mail (94.1% vs. 87.3%, p<0.001).Conclusions: Patients showed a distinct preference for completing postal questionnaires rather than being approached by telephone or e-mail. Younger patients accepted e-mail-based follow-up more often, but the majority of the youngest patients still preferred approaches other than by e-mail - See more at: http://www.pcronline.com/eurointervention/ahead-of-print/201510-06/patient-preference-regarding-assessment-of-clinical-follow-up-after-percutaneous-coronary-intervention-the-papaya-study
Bioresorbable Polymer-Coated Orsiro Versus Durable Polymer-Coated Resolute Onyx Stents (BIONYX):Rationale and design of the randomized TWENTE IV multicenter trial
Aim: The aim was to compare in a noninferiority trial the efficacy and safety of 2 contemporary drug-eluting stents (DESs): a novel, durable polymer-coated stent versus an established bioabsorbable polymer-coated stent. Methods and results: The BIONYX trial (ClinicalTrials.gov-no.NCT02508714) is an investigator-initiated, prospective, randomized, patient- and assessor-blinded, international, multicenter study in all-comer patients with all types of clinical syndromes and lesions who require percutaneous coronary interventions with DES. Patients at 7 study sites in the Netherlands, Belgium, and Israel were randomly assigned (1:1, stratified for gender and diabetes mellitus) to treatment with the novel, zotarolimus-eluting, durable polymer-coated Resolute Onyx stent that has a radiopaque, thin-strut, CoreWire stent platform versus the sirolimus-eluting, bioresorbable polymer-coated Orsiro stent (reference device) that has a very thin-strut, cobalt-chromium stent backbone. The primary end point is the 1-year incidence of the composite clinical end point target vessel failure consisting of cardiac death, target vesselârelated myocardial infarction, or clinically indicated target vessel revascularization. A power calculation, assuming a target vessel failure rate of 6.0% (noninferiority margin 2.5%), revealed that 2,470 study patients would give the study 80% power (α level 5%), allowing for up to 3% loss to follow-up. The first patient was enrolled on October 7, 2015; on December 23, 2016, the last patient entered the study. Conclusions: BIONYX is a large-scale, prospective, randomized, international, multicenter trial comparing a novel DES with durable coating versus a reference DES with biodegradable coating in all-comers. The study is the first randomized assessment of the Resolute Onyx stent, which is an often-used DES outside the United States
Comparison of eligible non-enrolled patients and the randomised TWENTE trial population treated with Resolute and XIENCE V drug-eluting stents
Aims: The TWENTE trial recently enrolled more than 80% of all eligible patients, who were randomised to zotarolimus-eluting Resolute or everolimus-eluting XIENCE V stents. In the present study, we investigated whether eligible, non-enrolled patients differed from the randomised TWENTE trial population in baseline characteristics and one-year outcome. Methods and results: Characteristics of 1,709 eligible patients were analysed. Independent external adjudication of clinical events was likewise performed for non-enrolled (n=318) and randomised patients (n=1,391). Non-enrolled and randomised patients did not differ in gender distribution, diabetes mellitus, and clinical presentation, but differed significantly in age and cardiovascular history. Nevertheless, clinical outcome after one year did not differ in the primary composite endpoint target-vessel failure (TVF; 9.8% vs. 8.1%; p=0.34), and its components cardiac death (1.6% vs. 1.2%; p=0.61), target vessel-related myocardial infarction (4.7% vs. 4.6%; p=0.92), and target-vessel revascularisation (3.8% vs. 3.0%; p=0.48). Previous bypass surgery predicted TVF in non-enrolled patients (p=0.001); removal of these patients resulted in identical TVF rates for non-enrolled and randomised patients (7.3% vs. 7.3%; p=0.99). Conclusions: Despite some differences in baseline characteristics, non-enrolled and randomised patients did not differ in one-year outcome, which was favourable for both populations and may be related to the drug-eluting stents used
A Randomized Controlled Trial in Second-Generation Zotarolimus-Eluting Resolute Stents Versus Everolimus-Eluting Xience V Stents in Real-World Patients : The TWENTE Trial
ObjectivesThe aim of this study was to compare the safety and efficacy of Resolute zotarolimus-eluting stents (ZES) (Medtronic Cardiovascular, Santa Rosa, California) with Xience V everolimus-eluting stents (EES) (Abbott Vascular Devices, Santa Clara, California) at 1-year follow-up.BackgroundOnly 1 randomized trial previously compared these stents.MethodsThis investigator-initiated, patient-blinded, randomized noninferiority study had limited exclusion criteria (acute ST-segment elevation myocardial infarctions not eligible). Patients (n = 1,391; 81.4% of eligible population) were randomly assigned to ZES (n = 697) or EES (n = 694). Liberal use of stent post-dilation was encouraged. Cardiac biomarkers were systematically assessed. The primary endpoint was target vessel failure (TVF), a composite of cardiac death, myocardial infarction not clearly attributable to non-target vessels, and clinically indicated target-vessel revascularization. An external independent research organization performed clinical event adjudication (100% follow-up data available). Analysis was by intention-to-treat.ResultsAcute coronary syndromes were present in 52% and âoff-labelâ feature in 77% of patients. Of the lesions, 70% were type B2/C; the post-dilation rate was very high (82%). In ZES and EES, TVF occurred in 8.2% and 8.1%, respectively (absolute risk-difference 0.1%; 95% confidence interval: â2.8% to 3.0%, pnoninferiority = 0.001). There was no significant between-group difference in TVF components. The definite-or-probable stent thrombosis rates were relatively low and similar for ZES and EES (0.9% and 1.2%, respectively, p = 0.59). Definite stent thrombosis rates were also low (0.58% and 0%, respectively, p = 0.12). In EES, probable stent thrombosis beyond day 8 was observed only in patients not adhering to dual antiplatelet therapy.ConclusionsResolute ZES were noninferior to Xience V EES in treating âreal-worldâ patients with a vast majority of complex lesions and âoff-labelâ indications for drug-eluting stents, which were implanted with liberal use of post-dilation. (The Real-World Endeavor Resolute Versus XIENCE V Drug-Eluting SteNt Study: Head-to-head Comparison of Clinical Outcome After Implantation of Second Generation Drug-eluting Stents in a Real World Scenario; NCT01066650
TCT-47 Two-Year Clinical Outcome of the TWENTE Trial, a Randomized Controlled Trial Comparing Second-Generation Zotarolimus-Eluting Resolute Stents Versus Everolimus-Eluting Xience V Stents in Real-World Patients
Background: In the prospective, randomized TWENTE trial, the zotarolimus-eluting Resolute stent was at 1 year follow-up non-inferior to the everolimus-eluting Xience V stent for the primary endpoint target vessel failure. This composite endpoint consisted of cardiac death, clinically indicated target vessel revascularization, or target vessel-related myocardial infarction (MI). So far, few long-term data of prospective head-to-head comparisons between both DES have been reported. Methods: Patients requiring percutaneous coronary interventions (PCI) with DES implantation at Thoraxcentrum Twente in Enschede were randomization between Resolute (Medtronic Vascular, Santa Rosa, CA, USA) and Xience V (Abbott Vascular, Santa Clara, CA, USA) in a 1:1 fashion. Inclusion of all coronary or bypass graft lesions and all clinical settings was permitted except for primary PCI (i.e. acute ST-elevation myocardial infarction (STEMI) was an exclusion criterion). Both external monitoring and clinical event adjudication were performed by an independent external contract research organization (Cardialysis, Rotterdam, the Netherlands). Two year clinical follow-up was performed as indicated in the study protocol. Results: A total of 1,391 patients were enrolled in the TWENTE trial between June 2008 and August 2010. The study population comprised 21.6% diabetics with a vast majority of complex lesions and âoff-labelâ indications for drug-eluting stents (77.4%). Patients presented with either stable angina (48.5%) or unstable angina/Non-STEMI (51.5%). Demographics, baseline angiographic and procedural data, and 2-year clinical follow-up data will be presented. This includes the primary endpoint of the study: Target vessel failure (TVF) at 2 year follow-up. Secondary endpoints include the individual components of the primary endpoint and the incidence of very late stent thrombosis. In addition, results of subgroup analyses will be reported. Conclusions: Results of pre-specified analyses of 2-year clinical outcome of the TWENTE trial will be presented at TCT 2012
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