Avaliação clínica inicial de novo balão farmacológico com sirolimus e nano partículas no tratamento de lesões reestenóticas / Initial clinical evaluation of a new sirolimus and nanoparticle pharmacological balloon in the treatment of restenosis lesions

INTRODUÇÃO: Recentemente, o conceito dos chamados balões farmacológicos tem sido testado no tratamento da reestenose intra stent, como uma alternativa de tratamento sem implante adicional de outra camada de metal no sítio previamente tratado. Ainda que os balões farmacológicos com paclitaxel tenham se mostrado eficazes para esta finalidade, esta tecnologia ainda apresenta alguns desafios: o paclitaxel é sabidamente menos efetivo e mais tóxico que outros fármacos anti-proliferativos, em especial quando comparado ao sirolimus e seus análogos/derivados. No presente estudo avaliamos um novo balão-farmacológico (Magic Touch), que utiliza sirolimus na dose de 1,27µg/mm2 , depositado em solução excipiente (nano partícula), na concentração de 1:1. MÉTODOS: Estudo prospectivo, multicêntrico, de braço único, incluindo pacientes com reestenose tanto de stents nãofarmacológicos como farmacológicos, tratados com balão Magic Touch. Não foram incluídas reestenoses do tipo oclusiva. Os pacientes foram submetidos a avaliação angiográfica e com ultrassom (USIC) aos seis meses. O desfecho primário foi a avaliação do grau de supressão neointinamal aos seis meses pela angiografia (perda luminal) e USIC (% de obstrução luminal). RESULTADO: Um total de 17 pacientes foram incluídos, sendo a maioria do sexo masculino (59%), com média de idade de 58 anos e com 60% de diabéticos. Metade da população tratada apresentava reestenose de stents farmacológicos e em 62% dos casos a reestenose era do tipo difusa/proliferativa. Sucesso angiográfico foi obtido em 100% dos casos. Aos 6 meses, a mediana da perda luminal tardia intra stent foi de 0,21mm [0,07; 0,51] ao passo que ao USIC, o% de obstrução luminal foi de 20% [18; 24]. Do ponto de vista clínico, ocorreu apenas um óbito, de causa não cardíaca. CONCLUSÃO: Neste estudo inicial em humanos, o balão farmacológico com sirolimus e nano partículas mostrou-se eficaz em reduzir a proliferação neointimal em pacientes com reestenose prévia de stents não-farmacológicos e/ou farmacológicos. (AU)

A randomized trial of creatine-kinase leak after rosuvastatin in elective percutaneous coronary intervention (CLEAR-PCI)

OBJECTIVES: To determine the impact of percutaneous coronary intervention (PCI) performed at the same time of the peak concentration of rosuvastatin to reduce periprocedural myocardial infarction (PMI). BACKGROUND: Prior studies suggest that a high dose of statin before PCI reduce periprocedural myocardial infarction. However, there is no information regarding the elective PCI performed at the time of the peak of statin concentration to reduce PMI. METHODS: From 2001 to 2013, at a single center in Brazil we enrolled 544 patients who underwent elective PCI and after exclusions for baseline biases in clinical and angiographic characteristics, yielding 528 patients, we prospectively randomly assigned them to either a high loading dose of Rosuvastatin before PCI (n = 264) or standard treatment (n = 264). After exclusions for biases in procedural characteristics a total of 487 patients underwent to end points analysis. The primary outcome was the incidence of MB fraction of creatine kinase (CK-MB) greater than three times the upper limit of normal.RESULTS:The primary end point occurred in 7.6% in the rosuvastatin and 4.8% in the control group (P = 0.200). There was a higher incidence in elevation of CK-MB than normal baseline in the rosuvastatin (67.1% vs 59.2%, P = 0.701). There was no difference in major adverse event (0% in the rosuvastatin group vs 0.8% in control).

Hipertensão arterial resistente: do conceito ao tratamento intervencionista / Resistant hypertension: from concept to interventional treatment

A hipertensão arterial sistêmica é um grave problema de saúde pública e constitui importante causa de morbidade e mortalidade cardiovasculares no Brasil e no mundo. Apesar dos avanços terapêuticos, apenas 30% dos pacientes atinge os níveis pressóricos recomendados. A redução da pressão arterial sistêmica comprovadamente reduz a incidência de doença arterial coronariana, insificiência cardíaca e acidente vascular cerebral, além de reduzir as taxas de óbito. Nesse contexto, a chamada hipertensão arterial resistente, constatada em 10 a cada 30% dos pacientes hipertensos, surge como entidade de difícil controle clínico e de alta relevância global...

Impact of arterial injury on neointimal hyperplasia after Zotarolimus-eluting stent implantation: an IVUS study

The amount of neointimal hyperplasia (NIH) correlates with the degree ofarterial injury after bare-metal stent (BMS) implantation. With first generationdrug-eluting stent (DES) this effect of arterial overstretch as assessed by balloonto-artery ratio (BAR) on NIH formation appears to be diminished; however theimpact of BAR on NIH following second generation DES remains unknown.Methods and results: From January to December 2006, 86 pts with 98 lesions(115 stents) underwent percutaneous coronary intervention (PCI) withintravascular ultrasound (IVUS) evaluation twelve months after zotarolimus-elutingstent (ZES) implantation. Arterial injury was defined as BAR, which wascategorised into two groups: high BAR (>1.15, n=47) and low BAR (<1.15, n=39).The aim of this study was to investigate the impact of arterial injury on NIHfollowing implantation of ZES. Least-squares linear regression was use to assessthe association between NIH and BAR at twelve months. Overall, mean age was60 years and 33% had diabetes mellitus, there were no significant differencesregarding other baseline characteristics between groups. At baseline, meanreference vessel diameter (2.62±0.5 mm vs. 2.35±0.4 mm, p=0.006) and nominalstent diameter (3.15±0.5 mm vs. 2.85±0.3 mm, p=0.002) were smaller in the highBAR group; and at twelve-month evaluation, lumen volume (110.7±91.9 mm3 vs.154.3±91.3 mm, p=0.002), stent volume (134.0±113.8 mm vs. 174.9±98.0 mm,p=0.005) and vessel volume (249.2±207.5 mm vs. 325.0±161.8 mm, p=0.003)were higher in high BAR group as compared to the low BAR group. Regardingpercentage of NIH obstruction, there was no significant difference in low BAR vs.high BAR group (15.2±14.3% vs. 12.5±10.1%, p=0.62). Finally, arterial injury asassessed by BAR was not significantly associated with the amount of NIH (R20.0025, p=0.88).

Continuous neointimal hyperplasia formation after five years ofdifferent generations of DES: is there enough evidence of late‘catch-up’?

Aims: The amount of neointimal hyperplasia (IH) following drug-eluting stent (DES)implantation correlates with the potency of the anti-proliferative drug, its kineticrelease as well as some individual characteristics, as the presence of diabetesmellitus (DM). Recently, some publications have suggested a continuous growth ofIH following DES, which in some cases, might result in late “catch-up”. The aim ofthis study was to assess, by means of serial intravascular ultrasound (IVUS) thetemporal course of IH formation following the implantation of two differentgeneration of DES (durable-polymer sirolimus-eluting stent [SES] andbiodegradable-polymer biolimus-eluting stent [BES]); and the role of diabetesmellitus in this scenario.Methods and results: Patients included in this study represent our single centerinitial experience with SES and BES. Twenty-five pts with single de novo lesions innative coronary arteries, with reference vessel diameter between 2.5 and 3.5 mmwere treated with Cypher-SES (n=12) and Biomatrix-BES (n=13), and underwentIVUS evaluation post procedure, at a mean of 9 months and 5 years. We onlyincluded patients with at least three serial IVUS acquisitions (post procedure, midand very long-term). Comparisons between baseline, first and second follow-up(FU) were done using the Friedman test and comparison between early and lateFU were done using the Wilcoxon test. The mean age was 59 years, with 28% ofDM. Stable coronary syndrome was the initial clinical indication for the majority ofthe cases (88%). Baseline characteristics did not differ between the groups.Overall, percentage of IH obstruction and IH volume markedly increased from midto long-term FU (percentage IH obstruction of 1.3% at 1st FU vs. 4.8% 2nd FU...

Angiographic and intravascular ultrasound predictors of sidebranch failure during PCI with provisional side branch stentingapproach in complex coronary bifurcation lesions

Previous randomised trials comparing single vs. double stenting inbifurcation lesions demonstrated cross-over from one to two stent strategy up to30% when single “provisional” stenting was primarily attempted. We sought toinvestigate the predictors of side branch (SB) failure in complex bifurcation lesionstreated with provisional stenting...

Comparative analysis of a distal protection system and the newstent M-Guard for the treatment of complex lesions in saphenousvein grafts

Aims: Percutaneous coronary intervention in saphenous vein grafts remain amajor challenge due to the high complication rates associated to the procedure.The new balloon-expandable MGuard™ stent was developed with an ultra-thinmesh sleeve attached to its outer surface, designed to reduce distal embolisationduring the procedure. Our objective was to evaluate the efficacy of the new deviceto prevent periprocedural embolic complications compared with a standardtreatment using a distal protection system.Methods and results: A consecutive cohort of patients with complex saphenousvein graft lesions treated with the MGuard™ stent were compared to patientstreated with bare metal stents and distal filter protection. The primary objectiveincluded the occurrence of major adverse cardiovascular events (composite ofdeath, non-fatal myocardial infarction and target lesion revascularisation) up to 30days of the procedure. Thirty-eight patients were evaluated, 16 in the MGuard™group and 22 patients in the distal filter protection group. Most patients were male(81.6%) and the mean age of the treated grafts was 10.4±5.6 years. Distal filterprotection group patients had longer lesions (17.4±6.3 mm vs. 26±16.2 mm;p=0.052) and higher thrombus burden (6.3% vs. 50%; p=0.005). There were nomajor adverse cardiac events in any of the groups up to 30 days of the procedure.Conclusions: The MGuard™ stent proved to be effective in the treatment ofcomplex saphenous vein graft lesions in our series of patients. Randomisedcomparisons with a larger number of patients must be carried out in the future toconfirm these preliminary results.

Comparative analysis of DES vs. bare metal stents for the treatment of STEMI- acute and mid-term outcomes

The use of drug eluting stents (DES) in primary percutaneous intervention(PCI) remains controversial. We sought to evaluate the acute and midterm (1year) safety and efficacy of DES versus bare metal stents (BMS) in the treatmentof acute STEMI.Methods and results: We enrolled 240 patients from two different institutions,one public (which only uses BMS because of government heathy policy) and oneprivate (that uses DES as the standard option for PCI), with acute STEMI whoundergone primary PCI. The primary end point was in hospital and 1 year rates ofmajor adverse cardiac events (MACE), defined as death, myocardial infarction(MI) and target lesion revascularisation (TLR). The clinical profile of patientsenrolled in the BMS group (n=169 pts) was more complex with higher incidence ofhypertension (73.3% vs. 60.5% p=0.06), previous MI (34.3% vs. 15.5% p<0.01),chronic renal insufficiency ( 26% vs. 12,8% p=0,03) and previous CABG (11.8%vs. 1,41% p=0,01). Also, patients in the BMS cohort had significant more PCIperformed by radial approach (20.7% vs. 0% p<0.01) while in the DES group thenumber of stents per patient was significantly higher...

Preliminary results of the multicentric, double-blinded,randomised, Vestasync II trial

Aims: Durable polymers in 1st generation DES have been linked to local coronaryinflammation that could ultimately result in life-threatening adverse events.Polymer-free DES systems have been developed as an attractive alternative tominimise these undesired effects. We sought to assess the safety and efficacy ofthe novel VESTAsync™ Eluting Stent (VES) combining a Cro-Co platform with ananothin-microporous hydroxyapatite surface coating impregnated with apolymer-free low-dose of Sirolimus (55μg). In its first-in-man (FIM) assessment, 15patients were enrolled and at the end of 8 months, late loss and% of stentobstruction considerably low (0.36mm and 4.0%, respectively) with this novelDES.Methods and results: The Vestasync II trial is a randomised (2:1), double-blindedmulticenter comparison of the VES to its platform, the Gen X stent, withmicroporous hydroxyapatite surface coating but without sirolimus. Patients wereeligible if they presented single de novo lesions in native coronary arteries with3.0-3.5mm diameter and ≤ 14mm in length. Primary endpoint was 9-month in-stentlate loss and% of stent obstruction. Lifelong AAS and 6-month clopidogrel wereprescribed to all pts. Seventy-five patients were enrolled. Baseline characteristicsincluded mean age of 57 years and 23% of diabetics. RVD and lesion length were2.67±0.4mm and 14.0±2.0mm. Procedure success was obtained in all cases.Three patients (4.2%) presented non-Q wave MI during hospitalisation with noother MACE. After discharge, there were two cases of TLR and no MI, death orstent thrombosis. Complete invasive follow-up was achieved for all patients. QCAand IVUS analysis are being processed by independent corelabs and detailedresults will be available at the meeting.Conclusions: In confirming the enthusiastic results of its FIM evaluation, theVESTAsync™ Sirolimus-Eluting Stent should be next evaluated in a larger trial withmore complex angiographic profile and clinical endpoints.

Acute myocardial infarction in progressively elderly patients. A comparative analysis of immediate results in patients who underwent primary percutaneous coronary intervention.

OBJECTIVE: Analysis of the in-hospital results, in progressively elderly patients who undergo primary percutaneous coronary intervention (PCI) in the first 24 hours of AMI. METHODS: The patients were divided into three different age groups (60/69, 70/79, and > or =80 years) and were treated from 7/95 until 12/99. The primary success rate and the occurrence of major clinical events were analyzed at the end of the in-hospital phase. Coronary stent implantation and abciximab use were employed at the interventionist discretion. RESULTS: We analyzed 201 patients with age ranging from 60 to 93 years, who underwent primary PCI. Patients with ages above 70 were more often female (p=.015). Those with ages above 80 were treated later with PCI (p=.054), and all of them presented with total occlusion of the infarct-related artery. Coronary stents were implanted in 30% of the patients. Procedural success was lower in > or =80 year old patients (p=.022), and the death rate was higher in > or =70 years olds (p=.019). Reinfarction and coronary bypass surgery were uncommon events. A trend occurred toward a higher combined incidence of major in-hospital events according to increased age (p=.064). CONCLUSION: Elderly patients (> or =70 years) presented with adverse clinical and angiographic profiles and patients > or =80 years of age obtained reduced TIMI 3 flow success rates after primary PTCA, and those > or =70 years had a higher death rate.

Lack of neointimal proliferation after implantation of sirolimus-coated stents in human coronary arteries: a quantitative coronary angiography and three-dimensional intravascular ultrasound study.

BACKGROUND: Restenosis remains an important limitation of interventional cardiology. Therefore, we aimed to determine the safety and efficacy of sirolimus (a cell-cycle inhibitor)-coated BX Velocity stents. METHODS AND RESULTS: Thirty patients with angina pectoris were electively treated with 2 different formulations of sirolimus-coated stents (slow release [SR], n=15, and fast release [FR], n=15). All stents were successfully delivered, and patients were discharged without clinical complications. Independent core laboratories analyzed angiographic and 3D volumetric intravascular ultrasound data (immediately after procedure and at 4-month follow-up). Eight-month clinical follow-up was obtained for all patients. There was minimal neointimal hyperplasia in both groups (11.0+/-3.0% in the SR group and 10.4+/-3.0% in the FR group, P:=NS) by ultrasound and quantitative coronary angiography (in-stent late loss, 0.09+/-0.3 mm [SR] and -0.02+/-0.3 mm [FR]; in-lesion late loss, 0.16+/-0.3 mm [SR] and -0.1+/-0.3 mm [FR]). No in-stent or edge restenosis (diameter stenosis >or=50%) was observed. No major clinical events (stent thrombosis, repeat revascularization, myocardial infarction, or death) had occurred by 8 months. CONCLUSIONS: The implantation of sirolimus-coated BX Velocity stents is feasible and safe and elicits minimal neointimal proliferation. Additional placebo-controlled trials are required to confirm these promising results.