京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20228号 / 医博第4187号 / 新制||医||1019(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 小池 薫, 教授 福原 俊一, 教授 湊谷 謙司 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24474号 / 医博第4916号 / 新制||医||1062(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 石見 拓, 教授 永井 洋士, 教授 大鶴 繁 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Purpose of Review: Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) have emerged as the invasive diagnostic tools of choice for hemodynamic assessment of the severity of CAD (coronary artery disease). We sought to comprehensively review the evidence on the utility of hemodynamic assessment of the coronary stenoses after percutaneous coronary intervention (PCI) using FFR/iFR, mechanisms of positive post-PCI iFR/FFR, and the clinical impact of significant residual ischemia. Recent Findings: The evidence on the utility of the post-PCI hemodynamic assessment has accumulated over the last few years. The post hoc analysis from the FAME 1 and FAME 2 data shows that higher post-PCI FFR is associated with better symptomatic improvement and lower event rate with larger increase in delta FFR (∆ FFR: post-PCI FFR – pre-PCI FFR). Unlike pre-PCI FFR, a consensus has not been established on the optimal value of post-PCI FFR, though multiple studies point toward better clinical outcomes with higher post-PCI FFR and larger ∆ FFR. Summary: Visual assessment of adequate stent apposition by coronary angiography is insufficient in evaluating for residual ischemia. The hemodynamic evaluation of residual ischemia by post-PCI FFR/iFR yields clinically relevant data and allows for appropriate post PCI optimization.

Bakgrund: Perkutan koronar intervention (PCI) är en etablerad behandling vid myokardiell infarkt men utförs även som planerat ingrepp vid angina pectoris. Efter en PCI kan patienten uppleva en förändrad livsvärld vilket kan påverka den psykiska hälsan negativt. Syfte: Syftet var att beskriva kranskärlspatienters upplevelser av psykisk hälsa inom det första året efter att ha genomgått PCI. Metod: En litteraturöversikt genomfördes som utgick från tolv artiklar med kvalitativ design där resultatet var byggt utifrån ett patientperspektiv. Publicering av artiklarna gjordes från 2008 till 2021. Data samlades in via databaserna Cinahl och Pubmed, vilken analyserades med hjälp av Fribergs analysmetod. Resultat: I resultatet framkom tre kategorier; ängslan över återhämtning efter utskrivning efter PCI, oro och rädsla över återgång till vardagen efter PCI samt en förändrad syn på livet efter PCI. Vidare identifierades sex underkategorier; behov av stöd och rehabilitering första tiden efter behandlingen, önskan om tillgänglig rådgivning om kvarvarande symtom och medicinering, osäkerhet i fysiska förmågor, rädsla över nya hjärthändelser, ökad meningsfullhet och drivkraft i att ta ansvar över levnadsvanor. Slutsats: Studien visar att behovet av tillgänglig rådgivning och uppföljning är en viktig faktor att beakta i patientens eftervård för att främja den psykiska hälsan. Vidare forskningsförslag är en intervjustudie för att kartlägga upplevda behov relaterat till tiden efter PCI. / Background: Percutaneous coronary intervention (PCI) is an established treatment of myocardial infarction but is also performed as a planned procedure during angina pectoris. After a PCI the patient may experience a changed life-world, which can negatively affect mental health. Aim: The aim was to describe coronary heart disease patients' experiences of mental health within the first year after undergoing PCI. Method: A literature review with a qualitative design was conducted including twelve studies that focused on the experiences from the perspective of the patients. The articles were published from 2008 to 2021. Data was collected through the databases Cinahl and Pubmed. Data was analyzed by the method of Friberg. Results: The results revealed three categories; anxiety about recovery after discharge after PCI, anxiety and fear over the return to everyday life after PCI, as well as a changed view of life after PCI. Furthermore, six subcategories were identified; need for support and rehabilitation the first time after the treatment, a desire for available advice on residual symptoms and medication, uncertainty in physical abilities, fear of new heart events, increased meaningfulness and the drive to take responsibility for lifestyle habits. Conclusion: The need for available counseling and follow-up is an important factor to consider to promote mental health. Further research to map perceived needs post PCI is needed.

No description available.

Cardiovascular disease is the leading cause of death worldwide and ischemic heart disease is the most common manifestation. Despite improved outcomes during the last decades, patients with acute coronary syndromes (ACS) are still at substantial risk of recurrent ischemic events and mortality. The aims of this thesis were to investigate the effect of the novel antiplatelet agent ticagrelor versus clopidogrel in patients with non-ST-elevation ACS (NSTE-ACS), overall and in relation to initial revascularization, and to explore this effect in relation to cardiac biomarkers. The impact of timing of revascularization in non-ST-elevation myocardial infarction (NSTEMI) was also studied, by assessing risk of mortality and recurrent myocardial infarction in relation to delay of percutaneous coronary intervention (PCI) in a nation-wide cohort. Finally, a novel clinical prediction model based on angiographic findings, biomarkers, and clinical characteristics was developed to estimate risk of ischemic events after performed revascularization. Ticagrelor treatment compared with clopidogrel was associated with a reduction in the composite endpoint of cardiovascular death/myocardial infarction/stroke and mortality alone, without any increase in overall major bleeding, but increased non-CABG-related major bleeding. The effect of ticagrelor over clopidogrel was consistent independent of initial revascularization. Elevated high-sensitivity cardiac troponin-T predicted benefit of ticagrelor over clopidogrel, while no difference between treatments was detected at normal levels. In patients with NSTEMI, PCI treatment within two days after hospital admission was associated with lower risk of all-cause death and recurrent myocardial infarction compared with delayed PCI. The new clinical prediction model included the following variables: prior vascular disease, extent of coronary artery disease, level of N-terminal pro-B-type natriuretic peptide and estimated glomerular filtration rate; and showed good discriminatory ability for the risk prediction of cardiovascular death/myocardial infarction/stroke and cardiovascular death alone. In conclusion, these results show that ticagrelor reduces the risk of recurrent ischemic events and mortality in patients with NSTE-ACS when compared with clopidogrel, and this effect seems independent of performed revascularization. The results also indicate that biomarkers could be used to select patients who would benefit most from more intense platelet inhibition. Furthermore, early PCI in NSTEMI seems to be associated with improved outcome. Finally, the novel clinical prediction model based only on four variables showed good discriminatory ability, which makes it a potentially effective and simple tool for tailored treatment based on individual risk of recurrent events.

INTRODUÇÃO: Os inúmeros avanços tecnológicos no tratamento percutâneo da doença coronariana aterosclerótica propiciaram que um crescente número de pacientes tratados previamente por angioplastia coronária transluminal percutânea (ACTP) seja referenciado à Cirurgia de Revascularização Miocárdica (CRM). Resultados de estudos a curto, médio e longo prazo confirmaram ou contestaram os efeitos negativos da angioplastia prévia com \"stent\" na mortalidade e morbidade da CRM. OBJETIVO: Avaliar a influência da intervenção coronária prévia com \"stent\", na mortalidade e ocorrência de eventos cardiovasculares e cerebrais maiores em pacientes com insuficiência coronária, submetidos à cirurgia de revascularização miocárdica, até cinco anos de seguimento. MÉTODO: Foi feito um levantamento retrospectivo a partir do banco de dados REVASC (Registro de reVAScularização mioCárdica) do Hospital Beneficência de São Paulo, dos pacientes consecutivos submetidos à CRM entre junho de 2009 a julho de 2010 e com seguimento em três fases: aos 30 dias, um ano e cinco anos. As características dos pacientes e os fatores de risco foram analisados, de acordo com as definições dadas às variáveis pelo EuroSCORE (\"The European System for Cardiac Operative Risk Evaluation\"). Para controlar eventual viés de seleção foi realizada análise agrupada com \"propensity score matching\". Todos os testes foram realizados considerando hipóteses bilaterais e assumindo um nível de significância alfa = 5%. RESULTADOS: Os pacientes foram divididos em dois grupos: CRM primária e com ACTP prévia. 261 (8,7%) de pacientes tiveram ACTP prévia. Na coorte original, no grupo com ACTP os pacientes são mais velhos (p=0,032) e têm mais doença arterial periférica (p < 0.001) e mais dislipidêmicos (p < 0,001) porem com o risco operatório EUROSCORE menor (p=0,031) e mais cirurgias não eletivas (=0,008). Após cinco anos, a mortalidade por causas cardiovasculares foi de 134 (5,6%) no grupo com ACTP prévia versus 13 (5,5%) no grupo de CRM primária; (p=0,946); a taxa de reinternação por causas cardiovasculares foi de 359 (15,0%) no grupo com ACTP prévia vs 47 (19,8%) no grupo de CRM primária; (p=0,048) e a taxa eventos combinados óbito/reinternação por causas cardiovasculares foi de 399 (16,7%) no grupo com ACTP prévia vs 51 (21,5%) no grupo de CRM primária; (p=0,057). Em seguida,foi realizada comparação na coorte pareada e em cinco anos a mortalidade por causas cardiovasculares foi de 17 (7,8%) no grupo com ACTP prévia vs 13 (5,5%) no grupo de CRM primária; (p=0,321); a taxa reinternação por causas cardiovasculares foi de 31 (14,2%) no grupo com ACTP prévia vs 47 (19,8%) no grupo de CRM primária; (p=0,113) e a taxa eventos combinados óbito/reinternação por causas cardiovasculares foi de 40 (18,4%) no grupo com ACTP prévia vs 51 (21,5%) grupo de CRM primária; (p=0,398). CONCLUSÃO: Em cinco anos de seguimento não houve diferença na mortalidade nos dois grupos, mas houve maior taxa readmissão por causas cardiovasculares no grupo com ACTP prévia. Essa diferença não foi confirmada na coorte pareada / BACKGROUND: several technological advances in percutaneous treatment of atherosclerotic coronary disease have led to an increasing number of patients treated with previous percutaneous intervention (PCI) referred to coronary artery bypass graft (CABG). Results of short-term initial studies showed negative effects of PCI on CABG outcomes .. Neverthless, further studies with immediate and long term follow-up confirmed or contested the negative influence on mortality and morbidity of CABG. OBJECTIVE: To evaluate the influence of previous coronary intervention with stent in the mortality and occurrence of major cardiovascular and cerebrovascular events in patients with coronary artery disease undergoing myocardial revascularization surgery, up to 5 years of follow-up. METHODS: A retrospective review was performed in the REVASC (Registro de rEVAScularização mioCárdica) database of patients undergoing coronary artery bypass grafting at the Hospital Beneficência Portuguesa de São Paulo, operated between June 2009 and July 2010, and followed in three periods: at 30 days, 1 year and 5 years. Patient characteristics and risk factors were analyzed according to the definitions given to the variables by EuroSCORE (The European System for Cardiac Operative Risk Evaluation). In order to control eventual selection bias, a simultaneous analysis with propensity score matching was performed. All tests were performed considering bilateral hypothesis and assuming a significance level ? = 5%. RESULTS: Patients were divided into two groups: primary CABG , 2746 patients and previous PCI. 261 (8.7%) of patients had previous PCI. In the original cohort, in the PCI group, patients were older (p = 0.032) and had more peripheral arterial disease (p < 0.001) and more dyslipidemic (p < 0.001) but with lower EUROSCORE operative risk (p = 0.031) and more non-elective surgeries (= 0.008). After five years, the mortality due to cardiovascular causes was 134 (5.6%) in the previous PCI group versus 13 (5.5%) in the primary CABG group; (p = 0.946); the rate of rehospitalization for cardiovascular causes was 359 (15.0%) in the group with previous PCI vs 47 (19.8%) in the primary CABG group; (p = 0.048) and the combined death / rehospitalization event due to cardiovascular causes was 399 (16.7%) in the group with previous PCI vs 51 (21.5%) in the primary CABG group; (p = 0.057). Then, we performed a paired cohort and in 5 years the mortality from cardiovascular causes was 17 (7.8%) in the group with previous PCI vs 13 (5.5%) in the primary CABG group; (p = 0.321); the rehospitalization rate for cardiovascular causes was 31 (14.2%) in the group with previous PCI vs 47 (19.8%) in the primary CABG group; (p = 0.113) and the combined death / rehospitalization event due to cardiovascular causes was 40 (18.4%) in the previous PCI group vs 51 (21.5%) primary CABG group; (p = 0.398). CONCLUSION: There is no statistically demonstrable difference in mortality over five years in both groups, but there was more readmission for cardiovascular causes and combined outcomes in the previous PCI group. In the matched cohort we cannot find any diferences

Introdução. A dupla antiagregação plaquetária traz benefícios no tratamento do infarto agudo do miocárdio com supradesnivelamento do segmento ST (IAMSST). Há variabilidade intra e interindividual no uso do clopidogrel e isso influencia no benefício do seu uso nesse grupo de pacientes. O objetivo desta pesquisa foi avaliar os efeitos de novo antiagregantes plaquetários (prasugrel e ticagrelor) administrados na sala de emergência (\"upstream\") sobre o resultado angiográfico da angioplastia primária, levando em conta o fluxo coronariano TIMI, o blush miocárdico e a carga de trombo. Métodos. Foi realizado um ensaio clínico, randomizado, cego, com 131 pacientes admitidos com IAMSST. Todos os pacientes receberam ácido acetilsalicílico (AAS). Os pacientes foram randomizados para receber clopidogrel (n=44), prasugrel (n=41) ou ticagrelor (n=46) como dose de ataque ainda na emergência. Todos os pacientes foram submetidos a aspiração manual de trombos. Ao término do procedimento, o resultado angiográfico foi avaliado quanto ao fluxo TIMI, o blush miocárdico e a carga de trombo. Resultados. O fluxo coronariano TIMI >= 1 antes do procedimento foi observado mais frequentemente com o uso de ticagrelor (n = 10, 21,7%) do que com o clopidogrel (n = 1, 2,3%) e prasugrel (n = 5, 12,2%; p = 0,019). O fluxo TIMI coronária no fim do procedimento não diferiu significativamente entre os grupos (p = 0,101). Melhor resultado no que diz respeito ao blush miocárdico foi observada com prasugrel, que produziu um grau de blush III em 85,4% (n = 35) dos pacientes, em comparação com o clopidogrel (54,5%; n = 24) e ticagrelor (67,4%; n = 31; p = 0,025). A carga de trombo pré-procedimento foi maior no grupo de clopidogrel, em que 97,7% (n = 43) dos casos denotaram carga de trombo grau 4/5, enquanto 87,8% (n = 36) do grupo prasugrel tiveram respostas semelhantes, e 80,4% (n = 37) foram observadas no grupo ticagrelor (p = 0,03). Conclusão. Os novos antiagregantes plaquetários ticagrelor e prasugrel parecem exercer efeito sobre o resultado angiográfico dos pacientes submetidos a angioplastia primária. O uso do ticagrelor propiciou menor carga de trombo e um fluxo TIMI melhor no pré-procedimento e o uso do prasugrel ensejou melhor perfusão miocárdica analisada pelo blush miocárdico. Não houve diferença no fluxo angiográfico TIMI pós procedimento / Introduction. Dual antiplatelet therapy has benefits in the treatment of acute myocardial infarction with ST-segment elevation (STEMI). There is variability intra and inter individual in the use of clopidogrel and this influences the benefit of its use in this group of patients. The objective of this research was to evaluate the angiographic results of Upstream Clopidogrel, Prasugrel, or Ticagrelor For Patients Treated With Primary Angioplasty. Methods. A clinical trial was conducted, randomized, double blind, with 131 patients admitted with STEMI. All patients received acetylsalicylic acid (ASA). Patients were randomized to receive clopidogrel (n = 44), prasugrel (n = 41) or ticagrelor (n = 46) as loading dose even in emergency. All patients were submitted to manual thrombus aspiration. At the end of the procedure, the angiographic result was evaluated for TIMI flow, myocardial blush and thrombus burden. Results. A coronary TIMI flow >= 1 before the percutaneous procedure was observed more frequently with the use of ticagrelor (n=10, 21.7%) than with clopidogrel (n=1, 2.3%) and prasugrel (n=5, 12.2%; p=0.019). The coronary TIMI flow at the end of the procedure did not significantly differ between the groups (p=0.101). A better result with respect to myocardial blush was observed with prasugrel, which yielded a blush grade of III in 85.4% (n=35) of patients, compared with clopidogrel (54.5%; n=24) and ticagrelor (67.4%; n=31; p=0.025). The pre-procedural thrombus burden was found to be of a higher grade in the clopidogrel group, in which 97.7% (n=43) of the cases exhibited thrombus burdens grade 4/5, whereas 87.8% (n=36) of the prasugrel group had similar responses, and 80.4% (n=37) were observed in the ticagrelor group (p=0.03). Conclusions. The novel antiplatelet agents represented by ticagrelor and prasugrel appear to have effect on the angiographic outcome of patients undergoing primary angioplasty. The use of ticagrelor led to a smaller thrombus burden and better TIMI flow at the beginning of the procedure and the use of prasugrel produced a better myocardial perfusion analyzed by myocardial blush. There was no difference in post angioplasty TIMI flow

As doenças cardíacas estão entre as condições crônicas consideradas como desafio para o setor saúde deste século e, nas próximas décadas, continuarão sendo a principal causa de morte global. Dentre as doenças cardiovasculares, a Doença Arterial Coronariana (DAC) é uma das mais importantes causas de morbimortalidade na população adulta. A Intervenção Coronária Percutânea (ICP) é uma das formas de tratamento da DAC. Deve ser acompanhada de medidas terapêuticas farmacológicas e não farmacológicas com o intuito de controlar a sua progressão e melhorar a qualidade de vida relacionada à saúde (QVRS). Objetivo. Comparar as medidas de QVRS e de sintomas de ansiedade e de depressão um ano após à ICP, de acordo com o tipo de intervenção recebida (rotina do serviço ou programa educativo com seguimento por telefone). Método. Estudo observacional, de delineamento longitudinal no qual acompanhamos a evolução dessas variáveis de interesse em pacientes submetidos à primeira ICP, entre agosto/2011 e junho/2012, atendidos em um hospital universitário do interior do Estado de São Paulo e que participaram de um estudo clínico aleatorizado. No estudo de intervenção, 30 pacientes participaram de um Programa Educativo com seguimento por telefone (grupo intervenção-GI) e outros 30 receberam informações de acordo com a rotina do serviço (grupo controle-GC) antes da realização da ICP. Doze meses após a intervenção, avaliamos 56 desses pacientes, sendo 29 do GI e 27 do GC. Os dados foram coletados por entrevistas individuais realizadas durante os retornos ambulatoriais ou nas residências dos participantes A QVRS foi avaliada pelo Medical Outcomes Study: 36-Item Short Form Survey (MOS-SF-36) e os sintomas de ansiedade e depressão pela Hospital Anxiety and Depression Scale (HADS), em suas versões validadas para o português. O teste T de Student para amostras independentes foi utilizado para comparar as medidas obtidas pelos instrumentos, segundo a participação ou não no Programa Educativo. O nível de significância adotado foi de 0,05. Resultados. Assim, como na avaliação feita antes da ICP, os grupos continuaram homogêneos nas caracterizações sociodemográficas obtidas, um ano após a intervenção. No GI, 58,6% eram homens, a média de idade foi de 64,6 anos e a maioria era casada (72,4%). No GC, 51,9% eram do sexo masculino, a média de idade foi 61,3 anos e 70,4% estavam casados. A avaliação da QVRS, 12 meses após a ICP, não mostrou diferenças estatisticamente significantes entre os dois grupos aos compararmos as médias dos oito domínios do SF-36. Em ambos os grupos, o domínio melhor avaliado foi Aspectos Sociais (M= 81,9 GI e M=72,7 GC; p=0,169) e o pior avaliado foi Aspectos Físicos (M= 55,2 GI e M=51,87 GC; p=0,777). Não constatamos diferenças entre os dois grupos também para as medidas de ansiedade (M= 6,33 GI e M=6,31 GC; p=0,981) e de depressão (M= 5,89 GI e M=5,31 GC; p=0,578). Conclusão. A participação em um programa educativo antes da ICP não teve efeito na determinação de uma melhor QVRS e menor presença de sintomas de ansiedade e de depressão, doze meses após a realização da intervenção / Cardiac illnesses figure among the chronic conditions that are considered challenging for this century\'s health sector and, in the upcoming decades, they will continue as the main global cause of death. Among the cardiovascular illnesses, Coronary Artery Disease (CAD) is one of the most important causes of morbidity and mortality in the adult population. Percutaneous Coronary Intervention (PCI) is one way to treat CAD. It should come with pharmacological and non-pharmacological measures to control its progression and improve the health-related quality of life (HRQoL). Objective. To compare the HRQoL measures and anxiety and depression symptoms one year after the PCI, according to the type of intervention received (usual care or educational program with telephone monitoring). Method. Observational study with longitudinal design, in which the evolution of these variables of interest was monitored in patients submitted to the first PCI between August/2011 and June/2012, who were attended at a university hospital in the interior of the State of São Paulo and who participated in a randomized clinical study. In the intervention study, 30 patients participated in an Educative Program with telephone monitoring (intervention group-IG) and 30 others received information according to the usual care (control group-CG) before the PCI. Twelve months after the intervention, 56 of these patients were assessed (being 29 from IG and 27 from CG). The data were collected through individual interviews, held during the outpatient return appointments or at the participants\' homes. The HRQoL was assessed using the Medical Outcomes Study: 36-Item Short Form Survey (MOS-SF-36) and the anxiety and depression symptoms using the Hospital Anxiety and Depression Scale (HADS), in its versions validated for Portuguese. Student\'s t-test for independent samples was used to compare the instrument measures according to the participation or not in the Educative Program. Significance was set at 0.05. Results. Like in the assessment preceding the PCI, the groups remained homogeneous in terms of sociodemographic characteristics one year after the intervention. In IG, 58.6% were male, the mean age was 64.6 years and the majority was married (72.4%). In CG, 51.9% were male, the mean age was 61.3 years and 70.4% were married. The HRQoL assessment 12 months after the PCI did not show statistically significant differences between the two groups when the means on the eight SF-36 domains were compared. In both groups, the best domain was Social Functioning (M= 81.9 IG and M=72.7 CG; p=0.169), while the worst was Physical Functioning (M= 55.2 IG and M=51.87 CG; p=0.777). No differences between the two groups were found for the anxiety (M= 6.33 IG and M=6.31 CG; p=0.981) and depression measures either (M= 5.89 IG and M=5.31 CG; p=0.578). Conclusion. The participation in an educative program before the PCI did not affect the determination of a better HRQoL and the lesser presence of anxiety and depression symptoms twelve months after the interview

INTRODUÇÃO: O sucesso a longo prazo da intervenção coronária percutânea, inicialmente realizada apenas com balão, era limitado pelo recolhimento elástico da artéria e pela hiperplasia neointimal. Com o advento dos stents convencionais (BMS) houve melhora nesse cenário e diminuição da reestenose, que é resultante de uma complexa cadeia de eventos iniciada após a injúria causada na parede vascular pela insuflação de balões e da aposição das hastes do stent. A proliferação excessiva de células musculares lisas (VSMC) tem papel fundamental na formação da neoíntima no contexto da reestenose intra-stent com a consequente redução da luz arterial. Com o advento dos stents farmacológicos (DES) houve diminuição importante da hiperplasia neointimal e um dos fármacos que se mostrou efetivo nesse papel é o sirolimo, que atua se ligando à proteína de ligação 12 e o heterodímero resultante se liga à mTOR impedindo sua ativação e causando parada do ciclo celular entre as fases G1 e S, desse modo inibindo a proliferação e migração de VSMC e das células endoteliais (HUVEC). Portanto a intervenção coronária acaba interferindo diretamente no endotélio, interferindo na produção das HUVEC não apenas no aspecto quantitativo, mas também na função das mesmas, e a qualidade funcional do endotélio é tão fundamental quanto à sua presença. Após o implante dos DES, principalmente os de primeira geração, ocorre disfunção endotelial cujo principal marcador é a perda da capacidade do relaxamento do vaso. Há correlação também entre cobertura das hastes incompleta e ocorrência de trombose dos stents. Consequentemente há espaço para o aprimoramento dos DES, para que se tornem dispositivos com eficácia já alcançada na prevenção da reestenose porém com um perfil de segurança maior. O presente trabalho tem como objetivo avaliar as alterações causadas pelos DES nas HUVEC e nas VSMC em cocultura na presença e na ausência do soro rico em plaquetas. MATERIAIS E MÉTODOS: Utilizamos células HUVEC e VSMC em modelos de monocultura e cocultura, na presença e na ausência de soro rico em plaquetas, tratadas com BMS ou DES. Realizamos a determinação da IC50 do inibidor da mTOR, avaliação da citotoxicidade pelo método colorimétrico do MTT, determinação da formação de peróxidos lipídicos, avaliação das fases do ciclo celular e da expressão de marcadores de controle de proliferação e inflamação. RESULTADOS: Na avaliação da citotoxicidade pelo método colorimétrico do MTT e determinação da IC50 as VSMC foram menos sensíveis ao sirolimo que as HUVEC (IC50 em 24/48 horas 14,85/10,47uM e 9,48/22,24 uM, respectivamente para HUVEC e VSMC). As plaquetas e fatores solúveis potencializam o estresse oxidativo gerado pela presença dos stents possivelmente por ampliar o ambiente inflamatório. Houve parada do ciclo celular na fase G0/G1 causada pelos DES somente com adição das plaquetas ao meio de cultura. Nos modelos de cultura celular sem as plaquetas a parada do ciclo celular foi em G2/M. Não houveaumento das células na fase DNA fragmentado (sub-G0) evidenciando que não houve indução de morte celular. CONCLUSÃO: As VSMC foram menos sensíveis ao sirolimo que as HUVEC. Nos modelos de cocultura com adição das plaquetas os DES eluídores de sirolimo causaram parada do ciclo celular na fase G0/G1 sem indução de morte celular, sugerindo que o sirolimo exerce seus efeitos anti-inflamatórios nessas populações celulares e consequentemente reduz a hiperplasia neointimal por um mecanismo citostático / INTRODUCTION: The long-term success of percutaneous coronary intervention, initially performed only with a balloon, was limited by the elastic recoil of the artery and by neointimal hyperplasia. There was improvement in this scenario with the advent of bare metal stents (BMS), because they decrease in restenosis, that resulting from a complex network of events initiated after the injury caused in the vascular wall by insufflation of balloons and apposition of the stent struts. Excessive proliferation of smooth muscle cells (VSMC) plays a key role in neointimal hyperplasia in the context of intrastent restenosis with consequent reduction of arterial lumen. With the advent of drug-eluting stents (DES) there was a significant decrease in neointimal hyperplasia and one of the drugs that proved effective in this role is sirolimus, which acts by binding to the binding protein 12 and the resulting heterodimer binds to mTOR preventing its activation and causing cell cycle arrest between G1 and S phases and thereby inhibiting the proliferation and migration of VSMC and also inhibiting endothelial cells (HUVEC). Therefore, coronary intervention interferes directly in the endothelium, interfering in the production of endothelial cells, not only in the quantitative aspect, but also in their function, and the functional quality of the endothelium is as fundamental as its presence. After the implantation of DES, especially those of the first generation, endothelial dysfunction occurs, whose main marker is the loss of the capacity of the vessel relaxation. There is also correlation between incomplete stem coverage and stent thrombosis. Consequently, it is possible to improve of the DES, so that they become devices with already achieved effectiveness in the prevention of restenosis but with a greater safety profile. The present study aims to evaluate the changes caused by DES in human HUVEC and VSMC in co-culture in the presence and absence of platelet-rich serum. MATERIALS AND METHODS: We used HUVEC and VSMC in monoculture and co-culture models in the presence and absence of platelet rich serum treated with BMS or DES. We performed the determination of IC50 for mTOR inhibitor, cytotoxicity evaluation by the colorimetric method of MTT, determination of lipid peroxide formation, cell cycle and expression of necrosis and inflammation markers. RESULTS: In the assessment of cytotoxicity by the MTT colorimetric method and determination of the IC50, VSMC were less sensitive to sirolimus than HUVEC (IC50 in 24/48 hours 14.85 uM/10.47uM and 9.48 uM/ 22.24 uM, respectively for HUVEC and VSMC). Platelets potentiate the oxidative stress generated by the presence of stents, possibly by increasing the inflammatory environment. Drug-eluting stents arrested VSMC and HUVEC in the G0/G1 phase of the cell cycle only with the addition of platelets to the culture medium. In cell culture models without platelets the cell cycle arrest was in G2/M. There was no increase of the cells in the fragmented DNA phase (sub-G0) evidencing that there was no induction of apoptosis. CONCLUSION: Human aorta smooth muscle cells of the were less sensitive to sirolimus than HUVEC. In coculture models with platelet addition, DES with sirolimus caused cell cycle arrest in the G0/G1 phase without induction of apoptosis, suggesting that sirolimus exerts its antiinflammatory effects in these cellular populations and consequently reduces neointimal hyperplasia via a cytostatic mechanism