Os resultados tardios com os stents farmacológicos são melhores do que com stents convencionais, principalmente no que se refere à reestenose. Entretanto, no mundo real, os stents farmacológicos são implantados em pacientes de maior complexidade, o que teoricamente já diminui a diferença dos resultados. Comparar resultados da utilização de stents com paclitaxel (Grupo I) em pacientes complexos com stents convencionais (Grupo II) implantados em pacientes menos graves. A partir dos resultados realizar análise para estimar a razão de custo-efetividade nos dois grupos. Foram analisados 220 pacientes prospectivamente durante aproximadamente dois anos (média de 17 meses): 111 do Grupo 1 (GI) e 109 do Grupo II (GII). Foram avaliadas a sobrevida e a sobrevida livre de eventos através do método de Kaplan-Meier. Usando-se os critérios da Organização Mundial de Saúde, calculou-se a razão custo-efetividade incremental (RCEI) para cada reestenose evitada. O escore de propensão foi usado para reduzir diferenças entre os dois grupos. Foi observado predomínio do sexo masculino nos dois grupos (n=174 66,8%), mas sem diferenças entre eles. Também não houve diferenças em relação à idade, que variou de 42 anos a 91 anos (65,9 anos). As diferenças que ocorreram, com maior incidência no GI foram: diabetes: GI=60 (50,4%) e GII=19 (17,4%), p=0,0001; história familiar para doença arterial coronariana (DAC): GI=43 (38,7%) e GII=24 (22,1%), p=0,007; infarto prévio: GI=54 (48,6%) e GII=31 (28,4%), p=0,002; cirurgia de revascularização prévia: GI=24 (21,7%) e GII=6 (5,5%), p=0,0005; angioplastia prévia: GI=28 (25,2%) e GII=17 (15,5%), p=0,077; síndromes coronarianas agudas: GI=48 (43,3%) e GII=35 (32,0%), p=0,088. Os pacientes triarteriais foram mais presentes no GI=21 (18,9%) do que no GII=11 (10,1%), p=0,029. No entanto, os pacientes do GII apresentaram mais frequentemente função normal do VE: GI=51 (45,9%) e GII=85 (77,9%), p=0,0001. Não houve diferença no número de lesões tratadas e entre o número de artérias por paciente, entre os dois grupos. O grupo dos stents convencionais abordou lesões mais simples: Tipo A GI=43 (25,6%); GII=65 (45,5%), p=0,0002; Tipo B: B1 GI=50 (29,7%) e GII=35 (24,5%), p=0,30; e B2 GI=51 (30,4%) GII=26 (18,1%), p=0,53; e Tipo C: GI=24 (14,3%) e GII=17 (11,9%), p=0,53. O número de reestenoses por paciente foi menor no GI=7 (6,3%) vs GII=14 (12,8%), mas sem significância estatística (p=0,099). Entretanto, a reestenose por lesão foi menor no GI=7 (4,1%) vs GII=14 (9,8%) p=0,0489. A sobrevida geral em dois anos foi 96,2% no GI e 89,3% no GII (p=0,76) e as sobrevidas livres de eventos foram similares: eventos maiores (p=0,35) e livre de reestenose (p=0,82). O escore de propensão demonstrou que pacientes com idade >72 anos, os diabéticos, as lesões com diâmetro <3,2mm e com o comprimento >18mm foram as variáveis que melhor classificaram pacientes para receber SF. Avaliando-se todos os fatores clínicos, angiográficos e técnicos através da curva de regressão logística, o único item de destaque foi o tamanho dos stents (OR=6,75 e RR=4,37). Com valor corrigido o GII tem 4,3 vezes maior chance de reestenose do que o GI. No que se refere aos custos, a árvore de decisão foi modelada na reestenose dos dois grupos GI=6,3% vs GII=12,8% em 17 meses (média). O benefício líquido do implante do stent com paclitaxel foi 6,3% de redução de reestenose, com incremento de custo de R$9.590,00. A razão custo-efetividade incremental (RCEI) foi R$147.538,00 por reestenose evitada, cujo valor incremental encontra-se acima do limiar sugerido pela OMS. Conclusões: Os resultados foram similares no GI e GII, mesmo o GI atendendo uma população mais grave, com mais diabéticos e outras comorbidades. A reestenose por lesão foi maior no GII. O tamanho do stent foi a única variável importante para a reestenose. O implante dos stents farmacológicos, em pacientes do mundo real, revelou-se uma estratégia não custo-efetiva. / Long term outcomes for drug eluting stents are better than those for bare metal stents, especially for restenosis. However, drug eluting stents are usually implanted in more complex patients, theoretically lessening the difference in the outcomes. To compare the outcomes of paclitaxel stents (GI) in complex patients and bare metal stents (GII), in less complex patients. For some two years (mean: 17 months), 220 patients were analyzed prospectively: 111 in GI and 109 in GII. Their general survival and cardiovascular event-free survival rates were assessed through the Kaplan-Meier method. Using the criteria of the World Health Organization (WHO), the incremental cost-effectiveness ratio (ICER) was calculated for each restenosis avoided. Propensity scores was used to reduce selection bias by equating both groups based on these covariates. Men predominated in both groups (n=174 66.8%), with no differences between them, including age, ranging from 42 to 91 years (65.9 years). The main differences, with higher rates in GI, were diabetes: GI=60 (50.4%) and GII=19 (17.4%), p=0.0001; family history: GI=43 (38.7%) and GII=24 (22.1%), p=0.007; previous acute myocardial infarction: GI=54 (48.6%) and GII=31 (28.4%), p=0.002; previous coronary artery bypass graft: GI=24 (21.7%) and GII=6 (5.5%), p=0.0005; previous angioplasty: GI=28 (25.2%) and GII=17 (15.5%), p=0.077; acute coronary syndrome: GI=48 (43.3%) and GII=35 (32.0%), p=0.088. Multivessel patients were more frequent in GI=21 (18.9%) than in GII=11 (10.1%), p=0.029. However, the GII patients presented normal left ventricle functions more frequently: GI=51 (45.9%) and GII=85 (77.9%), p=0.0001. There were no differences between the groups for the number of lesions treated and number of arteries per patient. The bare metal stent group presented simpler lesions: Type A GI=43 (25.6%); GII=65 (45.5%), p=0.0002; Type B: B1 GI=50 (29.7%) and GII=35 (24.5%), p=0.30; and B2 GI=51 (30.4%) GII=26 (18.1%), p=0.53; and Type C: GI=24 (14.3%) and GII=17 (11.9%), p=0.53. The restenosis per patient was lower in GI=7 (6.3%) than in GII=14 (12.8%), but without statistical significance (p=0.099). However, restenosis by lesion was lower in GI=7 (4.1%) than in GII=14 (9.8%) p=0.0489. The general two-year survival rate was 96.2% in GI and 89.3% in GII (p=0.76) with similar event-free survival rates: major events (p=0.35) and restenosis (p=0.82). The propensity score showed that it was better to receive SF in patients: age >72, diabetics and lesions with diameter <3,2mm and length >18mm. Assessing all the clinical, angiographic and technical factors through the logistic regression curve, the only the major predictor was stent size. With the value corrected, GII has 4.3 times more chances of restenosis than GI. In terms of costs, the decision tree was modeled on the restenosis in the two groups: GI=6.3% versus GII=12.8% in 17 months (mean). The net benefit of implanting of paclitaxel stents was a 6.3% reduction in restenosis, with a cost increase of R$ 9,590.00. The incremental cost-effectiveness ratio (ICER) was R$ 147,538.00 for avoided restenosis, whose incremental value exceeds the threshold suggested by the WHO (World Health Organization). The results were similar in GI and GII, despite more diabetes and other co-morbidities in GI. Restenosis by lesion was higher in GII. The size of the stent was the only important variable for restenosis. The use of drug eluting stents in patients is not a cost-effective strategy in actual practice.

Os resultados tardios com os stents farmacológicos são melhores do que com stents convencionais, principalmente no que se refere à reestenose. Entretanto, no mundo real, os stents farmacológicos são implantados em pacientes de maior complexidade, o que teoricamente já diminui a diferença dos resultados. Comparar resultados da utilização de stents com paclitaxel (Grupo I) em pacientes complexos com stents convencionais (Grupo II) implantados em pacientes menos graves. A partir dos resultados realizar análise para estimar a razão de custo-efetividade nos dois grupos. Foram analisados 220 pacientes prospectivamente durante aproximadamente dois anos (média de 17 meses): 111 do Grupo 1 (GI) e 109 do Grupo II (GII). Foram avaliadas a sobrevida e a sobrevida livre de eventos através do método de Kaplan-Meier. Usando-se os critérios da Organização Mundial de Saúde, calculou-se a razão custo-efetividade incremental (RCEI) para cada reestenose evitada. O escore de propensão foi usado para reduzir diferenças entre os dois grupos. Foi observado predomínio do sexo masculino nos dois grupos (n=174 66,8%), mas sem diferenças entre eles. Também não houve diferenças em relação à idade, que variou de 42 anos a 91 anos (65,9 anos). As diferenças que ocorreram, com maior incidência no GI foram: diabetes: GI=60 (50,4%) e GII=19 (17,4%), p=0,0001; história familiar para doença arterial coronariana (DAC): GI=43 (38,7%) e GII=24 (22,1%), p=0,007; infarto prévio: GI=54 (48,6%) e GII=31 (28,4%), p=0,002; cirurgia de revascularização prévia: GI=24 (21,7%) e GII=6 (5,5%), p=0,0005; angioplastia prévia: GI=28 (25,2%) e GII=17 (15,5%), p=0,077; síndromes coronarianas agudas: GI=48 (43,3%) e GII=35 (32,0%), p=0,088. Os pacientes triarteriais foram mais presentes no GI=21 (18,9%) do que no GII=11 (10,1%), p=0,029. No entanto, os pacientes do GII apresentaram mais frequentemente função normal do VE: GI=51 (45,9%) e GII=85 (77,9%), p=0,0001. Não houve diferença no número de lesões tratadas e entre o número de artérias por paciente, entre os dois grupos. O grupo dos stents convencionais abordou lesões mais simples: Tipo A GI=43 (25,6%); GII=65 (45,5%), p=0,0002; Tipo B: B1 GI=50 (29,7%) e GII=35 (24,5%), p=0,30; e B2 GI=51 (30,4%) GII=26 (18,1%), p=0,53; e Tipo C: GI=24 (14,3%) e GII=17 (11,9%), p=0,53. O número de reestenoses por paciente foi menor no GI=7 (6,3%) vs GII=14 (12,8%), mas sem significância estatística (p=0,099). Entretanto, a reestenose por lesão foi menor no GI=7 (4,1%) vs GII=14 (9,8%) p=0,0489. A sobrevida geral em dois anos foi 96,2% no GI e 89,3% no GII (p=0,76) e as sobrevidas livres de eventos foram similares: eventos maiores (p=0,35) e livre de reestenose (p=0,82). O escore de propensão demonstrou que pacientes com idade >72 anos, os diabéticos, as lesões com diâmetro <3,2mm e com o comprimento >18mm foram as variáveis que melhor classificaram pacientes para receber SF. Avaliando-se todos os fatores clínicos, angiográficos e técnicos através da curva de regressão logística, o único item de destaque foi o tamanho dos stents (OR=6,75 e RR=4,37). Com valor corrigido o GII tem 4,3 vezes maior chance de reestenose do que o GI. No que se refere aos custos, a árvore de decisão foi modelada na reestenose dos dois grupos GI=6,3% vs GII=12,8% em 17 meses (média). O benefício líquido do implante do stent com paclitaxel foi 6,3% de redução de reestenose, com incremento de custo de R$9.590,00. A razão custo-efetividade incremental (RCEI) foi R$147.538,00 por reestenose evitada, cujo valor incremental encontra-se acima do limiar sugerido pela OMS. Conclusões: Os resultados foram similares no GI e GII, mesmo o GI atendendo uma população mais grave, com mais diabéticos e outras comorbidades. A reestenose por lesão foi maior no GII. O tamanho do stent foi a única variável importante para a reestenose. O implante dos stents farmacológicos, em pacientes do mundo real, revelou-se uma estratégia não custo-efetiva. / Long term outcomes for drug eluting stents are better than those for bare metal stents, especially for restenosis. However, drug eluting stents are usually implanted in more complex patients, theoretically lessening the difference in the outcomes. To compare the outcomes of paclitaxel stents (GI) in complex patients and bare metal stents (GII), in less complex patients. For some two years (mean: 17 months), 220 patients were analyzed prospectively: 111 in GI and 109 in GII. Their general survival and cardiovascular event-free survival rates were assessed through the Kaplan-Meier method. Using the criteria of the World Health Organization (WHO), the incremental cost-effectiveness ratio (ICER) was calculated for each restenosis avoided. Propensity scores was used to reduce selection bias by equating both groups based on these covariates. Men predominated in both groups (n=174 66.8%), with no differences between them, including age, ranging from 42 to 91 years (65.9 years). The main differences, with higher rates in GI, were diabetes: GI=60 (50.4%) and GII=19 (17.4%), p=0.0001; family history: GI=43 (38.7%) and GII=24 (22.1%), p=0.007; previous acute myocardial infarction: GI=54 (48.6%) and GII=31 (28.4%), p=0.002; previous coronary artery bypass graft: GI=24 (21.7%) and GII=6 (5.5%), p=0.0005; previous angioplasty: GI=28 (25.2%) and GII=17 (15.5%), p=0.077; acute coronary syndrome: GI=48 (43.3%) and GII=35 (32.0%), p=0.088. Multivessel patients were more frequent in GI=21 (18.9%) than in GII=11 (10.1%), p=0.029. However, the GII patients presented normal left ventricle functions more frequently: GI=51 (45.9%) and GII=85 (77.9%), p=0.0001. There were no differences between the groups for the number of lesions treated and number of arteries per patient. The bare metal stent group presented simpler lesions: Type A GI=43 (25.6%); GII=65 (45.5%), p=0.0002; Type B: B1 GI=50 (29.7%) and GII=35 (24.5%), p=0.30; and B2 GI=51 (30.4%) GII=26 (18.1%), p=0.53; and Type C: GI=24 (14.3%) and GII=17 (11.9%), p=0.53. The restenosis per patient was lower in GI=7 (6.3%) than in GII=14 (12.8%), but without statistical significance (p=0.099). However, restenosis by lesion was lower in GI=7 (4.1%) than in GII=14 (9.8%) p=0.0489. The general two-year survival rate was 96.2% in GI and 89.3% in GII (p=0.76) with similar event-free survival rates: major events (p=0.35) and restenosis (p=0.82). The propensity score showed that it was better to receive SF in patients: age >72, diabetics and lesions with diameter <3,2mm and length >18mm. Assessing all the clinical, angiographic and technical factors through the logistic regression curve, the only the major predictor was stent size. With the value corrected, GII has 4.3 times more chances of restenosis than GI. In terms of costs, the decision tree was modeled on the restenosis in the two groups: GI=6.3% versus GII=12.8% in 17 months (mean). The net benefit of implanting of paclitaxel stents was a 6.3% reduction in restenosis, with a cost increase of R$ 9,590.00. The incremental cost-effectiveness ratio (ICER) was R$ 147,538.00 for avoided restenosis, whose incremental value exceeds the threshold suggested by the WHO (World Health Organization). The results were similar in GI and GII, despite more diabetes and other co-morbidities in GI. Restenosis by lesion was higher in GII. The size of the stent was the only important variable for restenosis. The use of drug eluting stents in patients is not a cost-effective strategy in actual practice.

Os vasos de fino calibre apresentam maior risco para reestenose e revascularização da lesão alvo. Limitações relacionadas com a navegabilidade dos sistemas de dilatação por balão e menor capacidade de acomodação da neoíntima podem contribuir para isto. O stent autoexpansível de nitinol Sparrow® dedicado a vaso de calibre < 2,75 mm, resultou num conjunto com perfil de um fio-guia 0,014\". Testado na forma de stent de metal puro no estudo CARE I, revelou-se seguro e eficaz em vasos de fino calibre. Este estudo avaliou, de forma pioneira, o despenho de um stent autoexpansível farmacológico neste cenário. O objetivo primário foi comparar a perda luminal tardia no vaso-alvo pela angiografia coronária quantitativa ao final de oito meses, entre os stents Sparrow® farmacológico e não farmacológico, em coronárias com diâmetro de referência < 2,75 mm. Casuística e métodos: Os pacientes foram randomizados de forma prospectiva em dois grupos para procedimento de angioplastia: um grupo com o emprego o stent Sparrow® farmacológico (sirolimus), e ou outro grupo com o stent Sparrow® na versão não farmacológica. Análise pela angiografia coronária quantitativa foi realizada imediatamente antes e após o procedimento e aos oito meses, com seguimento clínico de 24 meses. Foi utilizado o programa IBM SPSS Statistics® para análise estatística e foi considerado nível de significância de 5% e poder de 80% para o cálculo do tamanho da amostra. Resultados: 24 pacientes foram randomizados, 12 no grupo com stent farmacológico Sparrow® e 12 no grupo com a versão não farmacológica. Na avaliação angiográfica aos oito meses verificou-se significativa redução de perda luminal tardia no grupo com o stent farmacológico Sparrow® em comparação com grupo com a versão não farmacológica (0,25 + 0,16 mm versus 0,97 + 0,76 mm, p = 0,008, IC 95% de -1,19 ; -0,22). No seguimento clínico de 12 meses, não foram observados eventos cardíacos adversos maiores (morte, infarto ou necessidade de revascularização do vaso alvo) no grupo com stent farmacológico. Não ocorreu trombose intrastent. Conclusão: Em pacientes submetidos à angioplastia transluminal percutânea em artérias coronárias com diâmetro de referência < 2,75 mm, o emprego do stent farmacológico autoexpansível Sparrow®, em comparação com a versão não farmacológica do mesmo stent, resultou em significativa redução de perda luminal tardia, sem ocorrência de eventos clínicos que deponham contra a segurança do dispositivo pesquisado. / Small vessels represent a group with high risk for restenosis and target lesion revascularization. Limitations associated with navigability of balloon dilation systems and less accommodating of the neointima may contribute to this. The self-expanding Sparrow® stent system dedicated to the vessel size <2.75 mm resulted in a profile similar to a 0.014\" guide wire angioplasty. Tested as bare metal stent in the CARE trial I, the Sparrow® stent system has proved to be safe and effective in small vessels. This study evaluated, for the first time, the performance of a self-expanding drug eluting stent in this scenario. The primary objective was to compare the in-stent late lumen loss by quantitative coronary angiography at the end of eight months between the Sparrow® drug-elutig stent and Sparrow® bare metal stent in coronary arteries with reference diameter <=2.75 mm. Materials and methods: Patients were prospectively randomized (1:1) Analysis by quantitative coronary angiography was performed immediately before and after the procedure and at eight months with clinical follow-up to 12 months. We used the IBM® SPSS for statistical analysis and was considered a significance level of 5% and 80% power for the calculation of sample size. Results: 24 patients were randomized, 12 in each group. At Eight months follow-up there was significant reduction in late lumen loss in the Sparrow® drug-eluting stent group compared to the Sparrow® bare metal stent group (0.25 ± 0.16 mm vs. 0.97 + 0.76 mm, p = 0.008, 95% CI -1.19 to -0.22). Up to 12 months of clinical follow-up there no cases of death, myocardial infarction and target vessel revascularization Of note, there was no stent thrombosis. Conclusion: In patients undergoing percutaneous transluminal angioplasty in coronary arteries with reference diameter <= 2.75 mm, the use of Sparrow® drug-eluting stent, compared to the Sparrow® bare metal stent, resulted in significant less late loss without occurrence of clinical events that weigh against the security of device.

A doença arterial coronariana vem sendo a maior causa de mortalidade no mundo, a angioplastia com implante de stent é uma estratégia importante nestes casos. Estudos apontam a biodegradabilidade, imobilização de antiproliferativos e moléculas bioativas nos stents, como características das futuras gerações destes dispositivos. Dentre estas, o ácido hialurônico contribui para a diminuição da agregação e proliferação de células entre as camadas da artéria e o dispositivo implantado. Foram desenvolvidos modelos de stents coronários biorreabsorvíveis de poli(-L-ácido láctico) (PLLA) com enxertia de ácido hialurônico (HA) em poli(-ácido lático co-ácido glicólico) (PLGA) e poli(L-D-ácido lático) (PLDLA). Os modelos foram caracterizados quanto suas propriedades térmicas, mecânicas e de superfície. O PLDLA e PLGA com enxertia de HA modificado com dihidrazida adípica (ADH) apresentaram características de superfície mais hidrofílicas, ideais para material de revestimento dos dispositivos. Desta forma, este trabalho possibilitou o desenvolvimento dos modelos físicos biorreabsorvíveis, com dimensões semelhantes aos stents coronários, feitos de PLLA, revestidos com PLGA e PLDLA com enxertia de HA e HAADH, e estáveis aos processos de esterilização por radiação ultravioleta e plasma de peróxido de hidrogênio. / Coronary artery disease has been world´s leading cause of death and angioplasty stent implantation is an important strategy in these cases. Studies indicate that the biodegradability, immobilization of antiproliferatives and bioactive molecules in stents are characteristics of future generations of these medical devices. Amongst them, hyaluronic acid (HA) contributes to the decrease of the aggregation and proliferation of cells between artery layers and implanted device. For this purpose, poly (L-lactic acid) (PLLA) bioresorbable coronary stents with HA grafting in poly (lactic acid-co-glycolic acid) (PLGA) and poly (LD- (PLDLA) were developed. The models were characterized as their thermal, mechanical and surface properties. PLDLA and PLGA with adipic dihydrazide (ADH) modified HA grafting presented more hydrophilic surface characteristics, ideal as coating material of this devices. This project allowed the development of bioresorbable physical models with similar dimensions to coronary stents, made of PLLA, coated with PLGA and PLDLA with hyaluronic acid grafting, stable to ultraviolet radiation and plasma sterilization with hydrogen peroxide processes.

A disfunção endotelial é uma das possíveis causas relacionadas à taxa mais elevada de trombose após o implante da primeira geração de stents farmacológicos. Se a presença do polímero durável ou elevada dose de fármacos antiproliferativos, ou ambos, são responsáveis por este fenômeno não está definido. O Estudo VESTASYNC II comparou um novo stent farmacológico, com superfície revestida por uma camada porosa de hidroxiapatita e impregnado com baixa dose de sirolimus. (55?g - stent VestaSync®) com seu equivalente não farmacológico (Stent VestaCor® ). O Vestasync II é um estudo prospectivo, randomizado (2:1) e duplo-cego, que incluiu pacientes com lesões de novo em artérias nativas com extensão menor que 14mm, com diâmetro entre 3,0 e 3,5mm. Um subgrupo composto por 20 pacientes (10 em cada grupo) submeteu-se à avaliação da função endotelial, no seguimento angiográfico de oito meses. O objetivo primário foi a comparação da vasomotricidade após o implante de stents com a mesma plataforma, com e sem eluição de sirolimus, a fim de determinar o real impacto de baixa dose do sirolimus na função endotelial. O desfecho de eficácia foi a perda luminal tardia e o porcentual de obstrução intra-stent. A avaliação da função endothelial foi realizada através da estimulação atrial com marcapasso (20ppm acima da frequência cardiaca basal até alcançar 150ppm) e o diâmetro luminal foi mensurado nas extremidades proximal e distal do stent e em um segmento controle, em estágios diferentes (repouso, sucessivas fases do estímulo e após a infusão intracoronária de nitroglicerina). A eficácia deste novo dispositivo foi confirmada por angiografia coronária quantitativa (perda luminal tardia VestaSync = 0,39 mm vs. 0,78 mm, p=0,005) e ultrassom intravascular (% obstrução VestaSync 9,3% vs. 17,6%, p= 0,005). Houve variação negativa no diâmetro luminal, entre o repouso e o estímulo máximo, nas bordas proximal (10%) e distal (8%). Entre os segmentos controles esta variação não alcançou 3%. A eluição de dose baixa do sirolimus não parece interferir na função endotelial, oito meses após o implante do stent sem polímero revestido com hidroxiapatita. / Endothelium dysfunction is among the possible causes related to higher thrombosis rates after first generation drug-eluting stents implant. Whether the presence of durable polymer or high anti-proliferative drug dose, or both, can be responsible for this phenomenon is not clear. The VESTASYNC II trial compared a novel polymer-free drug-eluting stent with a nanothinmicroporous hydroxyapatite surface coating impregnated with a low-dose of sirolimus (55?g-VestaSyncTM stent) to a bare-metal equivalent also coated with a nanothin-microporous hydroxyapatite surface (VestaCorTM stent). This is a randomized (2:1), double-blinded trial which enrolled patients with single de novo lesions in native coronary arteries from 3.0 to 3.5mm diameter and less than 14mm in length. A subset of 20 patients (10 from each group) underwent to endothelial function assessment at eight-month angiographic follow-up. The primary objective was to compare the vasomotricity after implantation of stents with the same platform, with and without drug elution, to determine the real impact of low-dose sirolimus release in endothelial function. Efficacy endpoint was in-stent late loss and % of stent obstruction. Endothelial function was assessed with atrial pacemaker stimulation (20 ppm over basal cardiac frequency until reach 150 ppm) and the lumen diameter was measured at 5 mm of proximal and distal stent edges and in a control segment, in different stages (at rest, at successive phases of stimulli and after nitroglycerin intracoronary infusion). The efficacy of this new device was confirmed by means of quantitative coronary angiography (late loss VestaSync = 0.39 mm vs. 0.78 mm, p=0.005) and intravascular ultrasound (% obstruction VestaSync 9.3% vs. 17.6%, p= 0.005). There was a negative variation in luminal diameter between basal and maximum stimulli in proximal (10%) and distal (8%) edges of both groups. Among control segments this variation did not reach 3%. The elution of low-dose of sirolimus does not seem to interfere in endothelial function 8 months after polymer-free hydroxyapatite coating stent implantation.

La perturbation des écoulements au voisinage de la paroi artérielle équipée d'un stent joue un rôle prépondérant dans l'apparition et le développement des complications liées aux maladies cardiovasculaires (sténose, resténose, thrombose...). La topologie de l'écoulement dans ces régions est très complexe. En effet, au voisinage du stent, des zones de recirculation se forment en amont et aval de chaque branche et les contraintes pariétales y sont très faibles. Des études in vivo et in vitro ont mis en évidence le rôle de ces caractéristiques de l'écoulement intra-stent sur les maladies cardiovasculaires. Pour cela, la bonne estimation des contraintes pariétales et la compréhension du comportement de l'écoulement intra-stent et son rôle dans le transfert du principe actif devraient permettre d'optimiser les traitements (design de la prothèse, principe actif...). L'approche numérique est une voie très utile pour étudier ces phénomènes. Cependant, la bonne précision du calcul dépend du choix du modèle d'écoulement, des conditions aux limites, de la géométrie du stent et de l'artère pour réaliser une simulation pertinente.Nous étudions ici dans un premier temps l'effet du choix du modèle hémodynamique sur les caractéristiques de l'écoulement intra-stent. Trois modèles numériques décrivant l'écoulement coronaire ont été utilisés. Ces modèles sont : un modèle stationnaire "MP", le modèle pulsé simplifié "MPS" et le modèle pulsé complet "MPC" basé sur l'analyse de Womersley. Nous avons ainsi montré l'importance de la prise en compte de l'instationnarité de l'écoulement mais au dépens d'un temps de calcul très accru. Dans un second temps, nous étudions expérimentalement l'écoulement intra-stent en utilisant la technique de mesure "PIV". Cette étude expérimentale a permis de confirmer les résultats numériques précédents. Au final, nous examinons numériquement l'effet de la pulsatilitié de l'écoulement sur les flux massiques libérés par les faces d'une branche de stent actif. Cette étude numérique a mis en exergue l'importance du couplage entre les recirculations et le transfert de masse vers la paroi artérielle. / The disturbance of the flow in the vicinity of the arterial wall equipped with a stent plays a key role in the onset and development of complications related to cardiovascular diseases (stenosis, restenosis, thrombosis...). The topology of the flow field in the intra-stent zone is very complex. Indeed, in the vicinity of the stent, recirculation zones form upstream and downstream of the stent strut where wall shear stress is very low. In vivo and in vitro studies have demonstrated the role of the in-stent flow features on cardiovascular diseases.The correct estimation of the wall shear stress, the understanding of the behavior of the in-stent flow and its role in the transfer of the drug are expected to help optimize treatments (stent geometry, drug composition...). The numerical approach (CFD) is a useful and versatile way to study these phenomena. However, the accuracy and the relevance of the results depend on the choice of the flow model, the boundary conditions and the stent and artery geometry.Firstly we study in this work the impact of the hemodynamic model on the in-stent flow characteristics. Three numerical models describing the coronary flow are used. These models are: the steady model "MP", the simplified pulsatile model "MPS" and the complete pulsatile model "MPC" based on Womersley's analysis. We show the importance of the pulsatility of the flow but at the expense of a high increase in the computing time. Secondly we study experimentally the in-stent flow using measurement technique "PIV". This experimental study confirms the previous numerical results. Finally we examine numerically the effects of the flow pulsatility on the mass fluxes released by the faces of a drug eluting stent. This numerical study highlights the importance of the coupling between the recirculation zones and the mass transfer into the arterial wall.

Current economic evaluations do not explicitly acknowledge that there are multiple decision points throughout the lifecycle of new health technologies which, in the presence of uncertainty and irreversible consequences of those decisions, influence value. Real options analysis (ROA) has been proposed to overcome these limitations. However, applications to date all assumed that decisions influencing the arrival of information are made by the same actors making the decisions on adoption. The aim of this thesis is to explicitly incorporate into health technology assessment (HTA) the impact of uncertainty on decision making about new health technologies in the presence of irreversibilities. I present a series of analyses comparing “traditional” economic evaluation methods to applications of ROA using the case study of drug-eluting stents (DES). The conventional application of ROA allowed for flexibility in decisions incorporating all economic consequences of changing decisions. Over and above uncertainty surrounding the current estimate of value, three major components contributing to the economic value of the new technology were assumed to also change over time. This type of analysis can be used to determine the optimal initial decision allowing for changes in decisions and the optimal timing for review. However, it assumes that new information will always be revealed, regardless of the original decision on adoption. To reflect the combined impact of coverage, pricing and research decisions in HTA and therefore to make information arrival endogenous, a more complex approach is suggested: a Real Options Game (ROG) combining ROA with a game theoretical approach. In the ROG the HTA body and the manufacturer are assumed to play a sequential, incomplete information game, where the manufacturer has control over the arrival of information. The manufacturer decides whether to submit evidence, reduce price and conduct more research, while the HTA body decides on adoption. The DES analysis modelled a series of decision points between 2005 and 2010, with decisions not depending on hindsight, but allowing for predicted changes in value, incorporating a drift in information and responses by the other party. Payoffs were estimated for both players using a probabilistic Markov model. Optimal strategies incorporating the impact of earlier decisions on research were determined. HTA is a dynamic and interactive process, therefore results of the ROA analyses sometimes suggested a different course of action compared to traditional analyses. The best decision may depend on predictions of how other parties will react, as well as likely evolution of the evidence base and the costs of decision reversal.

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第12999号 / 論医博第2107号 / 新制||医||1016(附属図書館) / 32927 / (主査)教授 川上 浩司, 教授 古川 壽亮, 教授 小池 薫 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13207号 / 論医博第2161号 / 新制||医||1031(附属図書館) / (主査)教授 福原 俊一, 教授 湊谷 謙司, 教授 小池 薫 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

OBJECTIVES The aim of this analysis was to assess the 7-year long-term safety and effectiveness of a randomized comparison of percutaneous coronary intervention (PCI) with sirolimus-eluting stents (SES) versus minimally invasive direct coronary artery bypass (MIDCAB) surgery for the treatment of isolated proximal left anterior descending lesions. BACKGROUND Long-term follow-up data comparing PCI by SES and MIDCAB surgery for isolated proximal left anterior descending lesions are sparse. METHODS Patients were randomized either to PCI with SES (n ¼ 65) or MIDCAB (n ¼ 65). Follow-up data were obtained after 7 years with respect to the primary composite endpoint of death, myocardial infarction, and target vessel revas- cularization. Angina was assessed by the Canadian Cardiovascular Society classification and quality of life with Short Form 36 and MacNew quality of life questionnaires. RESULTS Follow-up was conducted in 129 patients at a median time of 7.3 years (interquartile range: 5.7, 8.3). There were no significant differences in the incidence of the primary composite endpoint between groups (22% PCI vs. 12% MIDCAB; p ¼ 0.17) or the endpoints death (14% vs. 17%; p ¼ 0.81) and myocardial infarction (6% vs. 9%, p ¼ 0.74). However, the target vessel revascularization rate was higher in the PCI group (20% vs. 1.5%; p < 0.001). Clinical symptoms and quality of life improved significantly from baseline with both interventions and were similar in magnitude between groups. CONCLUSIONS At 7-year follow-up, PCI by SES and MIDCAB in isolated proximal left anterior descending lesions yielded similar long-term outcomes regarding the primary composite clinical endpoint and quality of life. Target vessel revascularization was more frequent in the PCI group. (Randomied Comparison of Minimally Invasive Direct Coronary Artery Bypass Grafting and Percutaneous Coronary Intervention With Drug-Eluting Stents in Patients With Proximal Stenosis of the Left Anterior Descending Coronary Artery; NCT00299429) (J Am Coll Cardiol Intv 2014;-:-–-) © 2014 by the American College of Cardiology Foundation.