abcArquivos Brasileiros de CardiologiaArq. Bras. Cardiol.0066-782X1678-4170Sociedade Brasileira de Cardiologia - SBCSão Paulo, SP, BrazilZCbtJVYjCTsqX7N5p4zfJFQ00005S0066-782X2006000300005S0066-782X(06)0860030510.1590/S0066-782X2006000300005Artigos OriginaisInfluência do diabete melito nos resultados imediatos do implante de stent coronário: uma análise dos dados da Central Nacional de Intervenções Cardiovasculares (CENIC)MoscosoIsaacGarciaLázaro ClaudiovinoDouradoGilvan OliveiraMauroMaria Fernanda Z.CaramoriPauloCoelhoWilsonLimaValterBuenoRonaldoMangioneJosé A.São PauloSPCentral Nacional de Intervenções CardiovascularesSociedade Brasileira de Hemodinâmica e Cardiologia Intervencionista 0320068631811903003200529102004This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
OBJETIVO: Avaliar a influência do diabete melito (DM) nos resultados imediatos do implante de stent coronário (SC), de acordo com o quadro clínico de apresentação. MÉTODOS: Entre janeiro/1997 e dezembro/2003, segundo a Central Nacional de Intervenções Cardiovasculares (CENIC), 11.874 pacientes diabéticos foram submetidos a implante de SC: 7.386 (62,3%) com insuficiência coronária crônica (ICO), 3.142 (26,4%), em síndrome isquêmica instável sem elevação ST (SIASEST) e 1.346 (11,3%), com infarto agudo do miocárdio (IAM) com supradesnivelamento de ST. Estes grupos foram comparados com 48.103 não-diabéticos: 30.980 (64,5%) com ICO, 10.938 (22,7%) em SIASEST e 6.185 (12,8%) com IAM. RESULTADOS: Os diabéticos apresentaram características clínicas e angiográficas de maior risco. Os diabéticos com ICO apresentaram taxa de eventos adversos semelhantes aos não-diabéticos (0,98% x 0,91%, p=0,5971), porém, os diabéticos em SIASEST e IAM apresentaram maior incidência de eventos: 2,76% x 1,46% (p<0,0001) e 7,87% x 4,1% (p<0,0001), respectivamente. A análise multivariada mostrou o DM como preditor independente de risco para eventos adversos maiores na SIASEST (OR: 1,92 IC: 1,46-2,52 p<0,0001) e no IAM (OR: 2,0 IC: 1,57-2,54 p<=0,0001) e não na ICO (OR: 1,08 IC: 0,83-1,42 p=0,5470). CONCLUSÃO: Os pacientes diabéticos portadores de ICO apresentaram evolução hospitalar semelhante aos não diabéticos, porém, os com SIASEST e IAM demonstraram maior taxa de eventos cardíacos adversos comparados com a população não-diabética.
Influência do Diabete Melito nos resultados imediatos do implante de stent coronário: uma análise dos dados da Central Nacional de Intervenções Cardiovasculares (CENIC)
Isaac Moscoso; Lázaro Claudiovino Garcia; Gilvan Oliveira Dourado; Maria Fernanda Z. Mauro; Paulo Caramori; Wilson Coelho; Valter Lima; Ronaldo Bueno; José A. Mangione
CENIC - Central Nacional de Intervenções Cardiovasculares da Sociedade Brasileira de Hemodinâmica e Cardiologia Intervencionista - São Paulo, SP
Correspondência
RESUMO
OBJETIVO: Avaliar a influência do diabete melito (DM) nos resultados imediatos do implante de stent coronário (SC), de acordo com o quadro clínico de apresentação.
MÉTODOS: Entre janeiro/1997 e dezembro/2003, segundo a Central Nacional de Intervenções Cardiovasculares (CENIC), 11.874 pacientes diabéticos foram submetidos a implante de SC: 7.386 (62,3%) com insuficiência coronária crônica (ICO), 3.142 (26,4%), em síndrome isquêmica instável sem elevação ST (SIASEST) e 1.346 (11,3%), com infarto agudo do miocárdio (IAM) com supradesnivelamento de ST. Estes grupos foram comparados com 48.103 não-diabéticos: 30.980 (64,5%) com ICO, 10.938 (22,7%) em SIASEST e 6.185 (12,8%) com IAM.
RESULTADOS: Os diabéticos apresentaram características clínicas e angiográficas de maior risco. Os diabéticos com ICO apresentaram taxa de eventos adversos semelhantes aos não-diabéticos (0,98% x 0,91%, p=0,5971), porém, os diabéticos em SIASEST e IAM apresentaram maior incidência de eventos: 2,76% x 1,46% (p<0,0001) e 7,87% x 4,1% (p<0,0001), respectivamente. A análise multivariada mostrou o DM como preditor independente de risco para eventos adversos maiores na SIASEST (OR: 1,92 IC: 1,46-2,52 p<0,0001) e no IAM (OR: 2,0 IC: 1,57-2,54 p<=0,0001) e não na ICO (OR: 1,08 IC: 0,83-1,42 p=0,5470).
CONCLUSÃO: Os pacientes diabéticos portadores de ICO apresentaram evolução hospitalar semelhante aos não diabéticos, porém, os com SIASEST e IAM demonstraram maior taxa de eventos cardíacos adversos comparados com a população não-diabética.
A prevalência do diabete melito tem aumentado progressivamente nos últimos 20 anos e estima-se que existam no mundo, atualmente, 100 milhões de pessoas portadoras da doença1. Ela é fator de risco importante para aterosclerose generalizada e, por isso, as complicações cardiovasculares são as principais causas de óbito e incapacidade nesses pacientes2. Além disso, a doença coronária nos diabéticos tem um curso mais agressivo, levando a uma incidência de óbito de 45% em 7 anos e de 75%, em 10 anos após o início dos sintomas3.
Nos diabéticos, o resultado imediato e tardio após intervenção coronária percutânea (ICP) mostrava-se inferior quando comparado aos não-diabéticos4,5. Entretanto, atualmente, com o uso do stent coronário6, associado à terapêutica antiagregante plaquetária com aspirina, derivados tienopiridínicos e inibidores do receptor da glicoproteína IIb/IIIa7,8, houve melhora dos resultados, porém, ainda existem controvérsias do benefício desta associação na população diabética9.
A apresentação clínica da insuficiência coronária tem importância no prognóstico a curto e longo prazo nos pacientes diabéticos. Aqueles que apresentam quadros agudos têm maior risco de óbito e infarto não fatal10, e os com angina estável apresentam menor sobrevida a longo prazo11, com relação aos não-diabéticos. A idade e sexo foram a base para comparação entre estas duas populações na maioria dos estudos que utilizou a ICP como forma de tratamento. Com exceção do IAM, a grande maioria de séries publicadas de tratamento percutâneo em pacientes diabéticos associa o quadro clinico de apresentação (angina estável e instável), e poucos estudos analisam se a forma de apresentação clínica da doença coronária influencia nos resultados imediatos do tratamento percutâneo em pacientes diabéticos.
O objetivo deste estudo foi comparar os resultados imediatos do implante do stent coronário em pacientes diabéticos com os não-diabéticos, de acordo com o quadro clínico de apresentação.
MÉTODOS
Foram analisados os registros dos pacientes submetidos a implante de stent coronário, entre janeiro de 1997 e dezembro de 2003, da Central Nacional de Intervenções Cardiovasculares (CENIC), que pertence a Sociedade Brasileira de Hemodinâmica e Cardiologia Intervencionista, coletados através de contribuição espontânea de seus membros titulares e armazenados em um banco de dados. Foram excluídos da análise os pacientes tratados só com angioplastia com balão, por ter resultados subótimos quando comparados aos de implante de stent, além de ser um procedimento pouco usado nos últimos anos.
Na primeira análise, estes foram divididos em diabéticos (DM) e não-diabéticos (Não-DM), comparando-se as características clínicas, angiográficas e os resultados imediatos após o procedimento. Posteriormente, foram divididos de acordo com o quadro clínico de apresentação em três grupos: insuficiência coronária crônica (ICO), definida como angina estável, isquemia silenciosa, angina de recente começo e progressiva; Síndrome Isquêmica Miocárdica Instável sem elevação do ST (SIASEST) de médio e alto risco, de acordo com a classificação TIMI Risk Score12 e IAM não-Q; e infarto agudo do miocárdio (IAM), definido como infarto agudo com supradesnivelamento do segmento ST, submetido a angioplastia primária. Nestes grupos, comparou-se o resultado entre diabéticos e não-diabéticos.
O desfecho primário do estudo foi avaliar a incidência do evento composto: óbito, IAM e a necessidade de revascularização cirúrgica ou percutânea de emergência na fase hospitalar. Óbito foi definido como morte de qualquer etiologia, infarto agudo do miocárdio, como elevação da CK-MB > 3 vezes o valor normal13 e/ou desenvolvimento de alterações eletrocardiográficas, segundo os critérios Novacode14 (extensão do código de Minnesota). Em pacientes com IAM, o reinfarto foi definido como reelevação dos níveis da CK-MB13.
A análise estatística foi realizada através do programa Statistica para Windows, versão 5.0 (StatSoft Inc. Tulsa, Oklahoma, USA). As variáveis categóricas foram expressas como percentual e comparadas através do teste qui-quadrado de Pearson. As variáveis contínuas foram expressas como média ± desvio padrão e analisadas através do teste t de Student. Um valor de p<0,05 foi considerado como estatisticamente significativo. Posteriormente, realizou-se uma análise multivariada para o cálculo da "razão de chances" (odds ratio) da DM nos componentes do desfecho primário: óbito, IAM, necessidade de revascularização (cirúrgica ou percutânea), combinado óbito/IAM (eventos irreversíveis), e o total de eventos no grupo total e para cada forma clínica de apresentação.
RESULTADOS
Entre janeiro de 1997 e dezembro de 2003 foram registrados na CENIC, 59.977 pacientes submetidos a implante de stent coronário. Destes, 11.874(19,8%) eram diabéticos e 48.103 (80,2%) não-diabéticos. As características clínicas e angiográficas estão descritas na tabela 1. Os pacientes diabéticos apresentavam maior percentual de pacientes do sexo feminino, maior incidência de RM prévia, ATC prévia, disfunção severa do VE, doença coronária triarterial, lesões coronárias complexas (tipo C, trombo intracoronário, calcificação, bifurcação), lesões em pontes de veia safena, e utilizaram mais os inibidores da GP IIb/IIIa (p<0,05 para todas as comparações).
A taxa de sucesso angiográfico foi menor no grupo DM (98,5%) x não-DM (98,8%) (p=0,0037), entretanto, a porcentagem de estenose após o procedimento foi maior no grupo diabético, 8,89 ± 11,46 x 7,66 ± 10,56 (p<0,0001). O desfecho primário ocorreu em DM (2,23%) x não-DM (1,44%) (p<0,0001). Com relação aos componentes do desfecho primário, houve maior incidência de óbito (1,24% x 0,73%, p<0,0001), nova ICP (0,28% x 0,15%, p=0,0355) e uma tendência a uma maior taxa de IAM (0,61% x 0,48%, p=0,0835) na população diabética. A necessidade de revascularização cirúrgica (0,08% x 0,07%, p=0,7655) não apresentou diferença entre os grupos (fig. 1).
ANÁLISE DOS GRUPOS
ICO - Dos pacientes com ICO (n = 38.366), 7386 (19,2%) eram diabéticos e também apresentavam características clínicas e angiográficas desfavoráveis (tab. 2), como: idade, sexo feminino, RM e ATC prévia, doença triarterial, disfunção severa do VE, lesões tipo C, calcificação, bifurcação, e usaram mais abciximab (p<0,05 para todas as comparações). Quanto aos vasos tratados, também houve maior incidência de intervenção em pontes de veia safena (2,3% x 1,6%, p<0,0001) e menor incidência de intervenção em DA (42,2% x 44,1%, p=0,0399).
A taxa de sucesso angiográfico foi semelhante DM (98,8%) x não-DM (98,8%) (p=0,8555). O desfecho primário ocorreu em DM (0,98%) x não-DM (0,91%) (p= 0,5971). Quanto aos resultados imediatos, não houve diferença na incidência de óbito (0,26% x 0,29%, p=0,7532), IAM (0,41% x 0,41%, p=0,9241) ou necessidade de revascularização cirúrgica (0,05% x 0,07%; p=0,8017), porém, houve maior necessidade de nova ICP no grupo diabético (0,26% x 0,14%, p=0,0284) (fig. 2).
SIASEST - Dos pacientes com SIASEST (n = 14.080), 3142 (22,3%) eram diabéticos e, como no subgrupo ICO, apresentavam características clínicas e angiográficas desfavoráveis (tab. 3), como: idade, sexo feminino, RM e ATC prévia, doença triarterial, disfunção severa do VE, trombo intracoronário, lesão em bifurcação, e utilizaram mais abciximab (p<0,05). Quanto aos vasos tratados, houve uma maior incidência de intervenção em pontes de veia safena (3,8% x 3,1%, p=0,0349), assim como menor incidência de intervenção em DA (41,4% x 44,3%, p=0,0007).
A taxa de sucesso angiográfico foi semelhante, DM (98,1%) x não-DM (98,9%) (p=0,7757). O desfecho primário ocorreu em DM (2,76%) x não-DM (1,46%) (p<0,0001). Observou-se maior incidência de óbito nos diabéticos (1,50% x 0,64%, p<0,0001), no entanto, não ocorreu diferença no IAM (0,83% x 0,59%, p=0,1931) e na necessidade de revascularização cirúrgica (0,13% x 0,07%; p=0,5691) ou percutânea (0,32% x 0,16%, p=0,1088) (fig. 3).
IAM - O IAM, como quadro clínico de apresentação, esteve presente em 7.531 pacientes (12,5%), destes, 1.346 (17,8%) eram diabéticos. As características clínicas e angiográficas estão colocadas na tabela 4. Os pacientes diabéticos apresentavam características clínicas e angiográficas mais desfavoráveis (idade, sexo feminino, RM e ATC prévias, doença triarterial, choque cardiogênico, lesões calcificadas; p<0,05). Nos pacientes diabéticos, houve uma maior intervenção em pontes de veia safena (p<0,0001).
A taxa de sucesso angiográfico foi menor DM (97,6%) x não-DM (98,5%) (p=0,0244). Nesta população, o desfecho primário ocorreu em DM (7,87%) x não-DM (4,1%) (p<0,0001). Houve maior incidência de óbito (6,09% x 3,12%, p=0,0001) e reinfarto (1,26% x 0,68%, p=0,0444), sem diferença na necessidade de revascularização cirúrgica (0,15% x 0,06%, p=0,903) ou percutânea (0,37% x 0,24%, p=0,5903) (fig. 4).
A análise multivariada está colocada na tabela 5. O diabetes melito foi no grupo total um preditor independente de risco para óbito (OR 1,71 IC: 1,40 - 2,09; p<0,0001), IAM (OR 1,27 IC: 0,97 – 1,67; p=0,0740), nova revascularização (OR 1,65 IC: 1,15 - 2,38; p=0,0045), assim como óbito/IAM (OR 1,59 IC: 1,36 - 1,86; p<0,0001).
No grupo ICO, o DM não se mostrou como fator preditor para eventos adversos (p>0,05 para todas as avaliações).
No grupo SIASEST, a DM também foi preditor independente de risco para óbito (OR 2,36 IC: 1,60 - 3,47; p<0,0001), nova revascularização (OR 1,95 IC: 0,96 - 3,92; p=0,0410), óbito/IAM (OR 1,90 IC: 1,41 - 2,56; p<0,0001).
No grupo IAM, a DM foi preditor independente de óbito (OR 2,01 IC: 1,53 - 2,65; p<0,0001), IAM (OR 1,87 IC: 1,02 - 3,40; p=0,0276), óbito/IAM (OR 2,01 IC: 1,57 - 2,58; p<0,0001).
DISCUSSÃO
A análise dos nossos dados demonstrou que o DM tem um efeito adverso nos resultados imediatos do implante de stent coronário, quando comparado aos pacientes não-diabéticos, e estes resultados são semelhantes aos recentemente publicados na literatura9,15-17. Como em todas essas séries, os pacientes diabéticos apresentavam características clínicas e angiográficas desfavoráveis. É importante salientar que, apesar deste fato, o emprego dos stents coronários proporcionou uma taxa de sucesso angiográfico semelhante entre os grupos. Entretanto, após o procedimento, na análise angiográfica, os diabéticos mostraram uma maior porcentagem de estenose, fator associado com aumento da reestenose após ICP, mas ainda não estabelecido como preditor de eventos adversos imediatos.
Embora os pacientes diabéticos tenham utilizado mais inibidores da GP IIb/IIIa que os não-diabéticos (10,6% x 7,6%, p<0,0001), esta taxa é inferior a de outras séries publicadas na literatura. Mathew16 e cols. relataram o uso de inibidor IIb/IIIa em 25% dos 2694 diabéticos tratados no estudo PRESTO e Walton e cols.18, em 38% de 707 pacientes diabéticos tratados em um hospital comunitário em Washington. O beneficio dos inibidores IIb/IIIa nos pacientes diabéticos tem sido demonstrado por estudos randomizados7,8,19 e por séries não randomizadas18,20,21, e poderiam ter atuado favoravelmente se utilizados em um número maior de pacientes desta série.
Outro fato importante a ser salientado é a maior incidência de intervenção em enxertos cirúrgicos venosos nestes pacientes e, segundo Ahmed e cols.22, existe uma maior mortalidade em diabéticos submetidos a implante de stent em pontes de veia safena, desfavorecendo a evolução hospitalar destes pacientes. Provavelmente, o uso de sistemas de proteção, evitando a embolização distal, poderá melhorar esses resultados, quando aplicados rotineiramente nesta população.
Nos pacientes diabéticos com doença coronária crônica, não está ainda bem estabelecido o beneficio da revascularização miocárdica como estratégia inicial de tratamento23, excetuando-se os pacientes com doença coronária multiarterial (triarterial e biarterial, com acometimento da porção proximal da DA), lesão de tronco da coronária esquerda e disfunção ventricular importante24. O emprego de stents nos procedimentos de revascularização percutânea parece ter neutralizado o excessivo risco dos pacientes diabéticos, quando submetidos a angioplastia convencional com balão, porém, ainda existe uma pequena diferença quando comparados aos não-diabéticos.
A análise dos dados da CENIC não demonstrou o diabetes como fator de risco nos resultados imediatos após ICP. Nossos resultados são concordantes com Abizaid e cols.25, que analisaram pacientes randomizados no subgrupo stent do estudo ARTS, não encontrando diferença na incidência de eventos adversos na fase hospitalar nos pacientes diabéticos (neste estudo, aproximadamente 60% dos pacientes apresentavam angina estável/isquemia silenciosa). No entanto, Bayerl e cols.26, analisando 386 pacientes submetidos a implante de stent coronário, não demonstraram um aumento na mortalidade nos pacientes diabéticos, porém, houve um aumento na incidência de IAM pós-procedimento (7,4% x 1,9%, p=0,022), provavelmente devido a fenômeno de microembolização distal por maior quantidade de placa aterosclerótica, característica destes pacientes27.
O uso de inibidor da GP IIb/IIIa não parece influenciar os resultados neste grupo de pacientes, como demonstrado no trabalho de Lima e cols.28, nas síndromes isquêmicas estáveis (angina estável/isquemia silenciosa). Chaves e cols.29, no estudo DANTE, também não demonstraram beneficio da utilização de abciximab nos resultados imediatos, assim como na redução da hiperplasia neointimal seis meses após implante de stent em pacientes diabéticos. Neste estudo, apenas 23% dos pacientes apresentavam angina instável. Finalmente, Kastrati e cols.30 não encontraram benefício da utilização de abciximab, quando comparado com uma dose de ataque de clopidogrel de 600 mg no subgrupo de pacientes diabéticos com doença coronária crônica, submetidos a implante de stent. A análise destes resultados sugere que a utilização do inibidor da GP IIb/IIIa neste grupo de pacientes não deve ser baseada apenas pela presença do diabetes melito.
Diabetes e SIASEST - Este grupo de pacientes tem se beneficiado com um procedimento intervencionista precoce, associado ao uso de inibidores da GP IIb/IIIa, comparado ao tratamento clínico31. O diabetes melito produz alterações no sistema da coagulação que favorecem a trombose e diminuem a fibrinólise, aumentando assim o risco de óbito e IAM não fatal.
Nossos resultados demonstraram que os pacientes diabéticos também têm um risco maior de apresentar eventos adversos quando submetidos à intervenção percutânea, semelhante às outras séries publicadas. López-Minguez e cols.32, analisando 279 pacientes com angina instável, submetidos a ICP, encontraram maior incidência de óbito e IAM não fatal nos pacientes diabéticos, em três anos de acompanhamento clínico (11,6% x 4,6%, p=0,047). Uma análise pós-hoc do registro OASIS, feito por Malmberg e cols.33, também encontrou um aumento na mortalidade de 57% nos pacientes diabéticos com SIASEST.
Embora os diabéticos de nossa série apresentassem um perfil clínico e angiográfico adverso, outro fator que poderia ter influenciado nos resultados desfavoráveis foi a baixa utilização de inibidor da GP IIb/IIIA (11,9%), comparado-se com outras séries não randomizadas, como a de López-Minguez, que utilizou abciximab em 47,8% dos pacientes diabéticos. O emprego de stents coronários e do inibidor da GP IIb/IIIa tirofiban, no estudo TACTICS31 e no recentemente publicado SYNERGY34, associou-se com uma redução significativa do risco nos pacientes diabéticos com SIASEST, submetidos à intervenção percutânea.
Em nosso estudo, os pacientes com IAM e diabetes apresentaram resultados imediatos inferiores, concordantes com outras séries publicadas na literatura. Silva e cols.35 analisaram 104 pacientes submetidos a implante de stent primário, onde os diabéticos apresentaram uma maior incidência de MACE aos 30 dias (21% x 4%, p=0,009), especialmente trombose subaguda (18% x 1%, p=0,003). Harjai e cols.36 analisaram os resultados de 626 pacientes diabéticos da base de dados dos estudos PAMI e verificaram, na análise multivariada, que não houve diferença na mortalidade hospitalar, mas sim na mortalidade aos 6 meses (OR 1,53 - IC95%: 1,03-2,26, p=0,03). Marso e cols.16, analisando um total de 4.308 pacientes submetidos a ATC primária durante um período de 20 anos, observou também que o diabetes esteve associada com maior mortalidade hospitalar (12,7% x 6,9%, p<0,001) e esta se manteve elevada em todos os períodos de tempo em que foi dividida a análise.
O uso de stent e inibidores da GP IIb/IIIa também tem melhorado os resultados da ATC primária em pacientes diabéticos. No estudo ADMIRAL37, o uso de abciximab em pacientes submetidos a implante de stent no IAM, esteve associado com uma redução relativa do risco de 67% nos pacientes diabéticos e no estudo CADILLAC38, de 44%. Provavelmente no futuro, o emprego de novas modalidades de intervenção percutânea no IAM (sistemas de trombectomia, proteção distal, oxigênio líquido supersaturado, e hipotermia sistêmica) poderá melhorar ainda mais os resultados nestes pacientes.
Nossos resultados concordam com trabalhos previamente publicados em relação ao diabetes e intervenção coronária percutânea na prática atual. Shaw e cols.39, analisando 100.253 procedimentos registrados na base de dados da ACC-NCDR, encontram o diabetes melito como preditor independente de morte na fase hospitalar (OR: 1,41 IC: 1,10-1,91 p<0,0001), porém não foram realizadas análises de acordo com o quadro clínico de apresentação. No nosso estudo, entretanto, a análise multivariada não demonstrou maior risco nos pacientes diabéticos portadores de doença coronária crônica, submetidos à intervenção coronária percutânea, fato não reportado antes na literatura mundial.
Existem algumas limitações no presente trabalho, pois se trata de uma análise retrospectiva e, por ser um registro nacional, podem existir diferenças nas rotinas e condutas dos serviços de cardiologia intervencionistas participantes do registro da CENIC, entretanto, reflete a prática atual da intervenção coronária percutânea em nosso País. Outra limitação ao estudo é a falta de evolução tardia dos doentes tratados; a CENIC só tem os resultados imediatos dos procedimentos percutâneos, que nos permite avaliar sua segurança e eficácia no período hospitalar, porém, não dispomos da evolução tardia dos pacientes, fato que consideramos importante para uma melhor avaliação dos resultados do tratamento em diabéticos.
Concluímos que o diabetes melito ainda constitui um fator independente de risco nos pacientes submetidos à intervenção coronária percutânea na pratica atual. Porém, no grupo de menor risco, este panorama está sendo revertido com o uso dos stents coronários, juntamente com a terapêutica farmacológica adjunta.
Devemos aguardar os resultados de novas estratégias de tratamento, como: stents eluídos com medicamentos, dispositivos de proteção, novas drogas antitrombóticas, associadas ao rigoroso controle metabólico e dos fatores de risco, como parte do tratamento multidisciplinar do diabetes melito.
Agradecimentos
Aos membros titulares da SBHCI que participaram do registro nacional CENIC. Divulgados na versão online dos Arquivos (www.arquivosonline.com.br).
José A. Mangione
Rua Comendador Elias Jafet , 415
05653 - 000 – São Paulo , SP
E-mail:
uci@uol.com.br
Recebido em 29/10/04
Aceito em 30/03/05
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Medicina 2003; 39: 640-5.Cardiovascular risk in diabetes mellitus during one-year period after acute coronary syndromeMedicina2003640539ZaliunasRBabarskieneMRLuksieneD11. Haffner SM, Lehto S, Ronnemaa T et al. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetics subjects with and without prior myocardial infarction . N Eng J Med 1998; 339: 229-34.Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetics subjects with and without prior myocardial infarctionN Eng J Med199822934339HaffnerSMLehtoSRonnemaaT12. Braunwald E. Unstable angina: A classification. Circulation 1989; 80: 410.Unstable angina: A classificationCirculation198941080BraunwaldE13. Myocardial infarction redefined-a consensus document of The Joint European Society of Cardiology/American College of Cardiology Commitee for the redefinition of myocardial infarction. Eur Heart J 2000; 21: 1502-13.Eur Heart J20001502132114. 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Diabetes mellitus is associated with a shift in the temporal risk profile of inhospital death after percutaneous coronary intervention: An analisis of 25.223 patients over 20 years. Am Heart J 2003; 145: 270-7.Diabetes mellitus is associated with a shift in the temporal risk profile of inhospital death after percutaneous coronary intervention: An analisis of 25. 223 patients over 20 yearsAm Heart J20032707145MarsoSPGiorgiLVJohnsonWI17. Mathew V, Gersh BJ, Williams BA et al. Outcomes in patients with diabetes mellitus undergoing percutaneous coronary intervention in the current era. A report from the Prevention of REStenosis with Tranilast and its Outcomes (PRESTO) trial. Circulation. 2004; 109: 476-80.Outcomes in patients with diabetes mellitus undergoing percutaneous coronary intervention in the current era: A report from the Prevention of REStenosis with Tranilast and its Outcomes (PRESTO) trial.Circulation.200447680109MathewVGershBJWilliamsBA18. Walton BL, Mumm K, Taniuchi M et al. Diabetic patients treated with abciximab and intracoronary stenting. Catheter Cardiovasc Interv. 2002; 55: 321-5.Diabetic patients treated with abciximab and intracoronary stentingCatheter Cardiovasc Interv.2002321555WaltonBLMummKTaniuchiM19. Roffi M, Moliterno DJ, Meier B et al. Impact of different platelet glycoprotein IIb/IIIa receptor inhibitor among diabetic patients undergoing percutaneous coronary intervention: Do Tirofiban and ReoPro Give Similat Efficacy Outcomes Trial (TARGET) 1-year follow-up. Circulation. 2002; 105: 2730-6.Impact of different platelet glycoprotein IIb/IIIa receptor inhibitor among diabetic patients undergoing percutaneous coronary intervention: Do Tirofiban and ReoPro Give Similat Efficacy Outcomes Trial (TARGET) 1-year follow-upCirculation.200227306105RoffiMMoliternoDJMeierB20. Velianou JL, Mathew V, Wilson SH et al. Effect of abciximab on late adverse events in patients with diabetes mellitus undergoing stent implantation. Am J Cardiol. 2000; 86: 1063-8.Effect of abciximab on late adverse events in patients with diabetes mellitus undergoing stent implantationAm J Cardiol.20001063886VelianouJLMathewVWilsonSH21. Hernandez JM, Dominguez A, Jimenez-Navarro MF et al. Does abciximab improve the prognosis of diabetics after percutaneous coronary intervention?. Rev Esp Cardiol. 2002; 55: 810-5.Does abciximab improve the prognosis of diabetics after percutaneous coronary intervention?Rev Esp Cardiol.2002810555HernandezJMDominguezAJimenez-NavarroMF22. Ahmed JM, Hong MK, Mehran R et al. Influence of diabetes mellitus on early and late clinical outcomes in saphenous vein graft stenting. J Am Coll Cardiol. 2000; 36: 1186-93.Influence of diabetes mellitus on early and late clinical outcomes in saphenous vein graft stentingJ Am Coll Cardiol.200011869336AhmedJMHongMKMehranR23. Ghosh J, Weiss M, Kay R et al. Diabetes mellitus and coronary artery disease. Therapeutic considerations. Heart Dis 2003; 5: 119-23.Diabetes mellitus and coronary artery disease: Therapeutic considerationsHeart Dis2003119235GhoshJWeissMKayR24. Fihn SD, Wiliams SV, Daley J et al. Guidelines for the management of patients with chronic stable angina: treatment. Ann Intern Med 2001; 135: 616-32.Guidelines for the management of patients with chronic stable angina: treatmentAnn Intern Med200161632135FihnSDWiliamsSVDaleyJ25. Abizaid A, Costa MA, Centemero M et al. Clinical and economic impact of diabetes mellitus on percutaneous and surgical treatment of multivessel coronary disease patients. Insights from the Arterial Revascularization Therapy Study (ARTS) Trial. Circulation 2001; 104: 533-8.Clinical and economic impact of diabetes mellitus on percutaneous and surgical treatment of multivessel coronary disease patients: Insights from the Arterial Revascularization Therapy Study (ARTS) Trial.Circulation20015338104AbizaidACostaMACentemeroM26. Bayerl DM, Siqueira E, Moscoso I et al. 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Chaves AJ, Sousa AG, Mattos LA et al. Volumetric analysis of in-stent intimal hyperplasia in diabetic patients treated with or without abciximab. Circulation 2004: 109: 861-6.Volumetric analysis of in-stent intimal hyperplasia in diabetic patients treated with or without abciximabCirculation20048616109ChavesAJSousaAGMattosLA30. Kastrati A, Mehilli J, Schühlen H et al. A clinical trial of abciximab in elective percutaneous coronary intervention after pretreatment with clopidogrel. N Engl J Med 2004; 350: 232-8.A clinical trial of abciximab in elective percutaneous coronary intervention after pretreatment with clopidogrelN Engl J Med20042328350KastratiAMehilliJSchühlenH31. Cannon C, Weintrub W, Demopoulos Laura et al for the TACTICSThrombolysis in Myocardial Infarction 18 Investigators. Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein iib/iiia inhibitor tirofiban. N Eng J Med 2001; 344: 1879-87.for the TACTICS-Thrombolysis in Myocardial Infarction 18 Investigators: Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein iib/iiia inhibitor tirofibanN Eng J Med2001187987344CannonCWeintrubWDemopoulosLaura32. López-Minguez JR, Fuentes ME, Doblado M et al. Papel pronóstico de la hipertensión arterial y de la diabetes mellitus en los pacientes con angina inestable tratados con stents coronarios. Rev Esp Cardiol 2003; 56: 987-94.Papel pronóstico de la hipertensión arterial y de la diabetes mellitus en los pacientes con angina inestable tratados con stents coronariosRev Esp Cardiol20039879456López-MinguezJRFuentesMEDobladoM33. Malmberg K, Yusuf S, Gerstein HC et al for the OASIS Registry Investigators. Impact of diabetes on long-term prognosis in patients with unstable angina and non-Q wave myocardial infarction. Results of the OASIS Registry. Circulation 2000; 102: 1014-9.for the OASIS Registry Investigators: Impact of diabetes on long-term prognosis in patients with unstable angina and non-Q wave myocardial infarction Results of the OASIS Registry.Circulation200010149102MalmbergKYusufSGersteinHC34. The SYNERGY Trial Investigators. Enoxaparin vs unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes managed with an intended early invasive strategy. JAMA 2004; 292: 45-54.Enoxaparin vs unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes managed with an intended early invasive strategyJAMA2004455429235. Silva JA, Ramee SR, White CJ et al. Primary stenting in acute myocardial infarction: influence of diabetes mellitus in angiographic results and clinical outcomes. Am Heart J 1999; 138: 446-55.Primary stenting in acute myocardial infarction: influence of diabetes mellitus in angiographic results and clinical outcomesAm Heart J199944655138SilvaJARameeSRWhiteCJ36. Harjai KJ, Stone GW, Boura J et al. Comparison of outcomes of diabetic and nondiabetic patients undergoing primary angioplasty for acute myocardial infarction. Am J Cardiol 2003; 91: 1041-5.Comparison of outcomes of diabetic and nondiabetic patients undergoing primary angioplasty for acute myocardial infarctionAm J Cardiol20031041591HarjaiKJStoneGWBouraJ37. Montalescot G, Barragan P, Wittenberg O et al. Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction. N Engl J Med 2001; 344: 1895-903.Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarctionN Engl J Med20011895903344MontalescotGBarraganPWittenbergO38. Stone GW, Grines CL, Cox DA et al. Comparison of angioplasty with stenting, with or without abciximab, in acute myocadial infarction. N Eng J Med 2002; 346: 957-66.Comparison of angioplasty with stenting, with or without abciximab, in acute myocadial infarctionN Eng J Med200295766346StoneGWGrinesCLCoxDA39. Shaw RE, Anderson V, Brindis RG on behalf of the ACC-NCDR. Development of a risk adjustment mortality model using the American College of CardiologyNational Cardiovascular Data Registry (ACCNCDR) Experience: 19982000. J Am Coll Cardiol 2002; 39: 1104-12.Development of a risk adjustment mortality model using the American College of Cardiology-National Cardiovascular Data Registry (ACC-NCDR) Experience: 1998-2000J Am Coll Cardiol200211041239ShawREAndersonVBrindisRGOriginal ArticlesInfluence of Diabetes Mellitus on immediate results of coronary stent: National Center for Cardiovascular Interventions (CENIC) data analysis
OBJECTIVE: This study sought to investigate the influence of Diabetes Mellitus (DM) on immediate results after coronary stenting implantation (CSI) according to clinical presentation. METHODS: Between January, 1997 and December, 2003, 11,874 diabetic patients underwent CSI, as recorded by CENIC database: 7,386 (62.3%) had chronic coronary disease (CCD); 3,142 (26.4%) acute coronary syndrome with non-ST segment elevation (ACSNST); and 1,346 (11.3%), reported acute myocardial infarction (AMI), with ST Segment elevation. Those groups were compared with 48,103 non-diabetics: 30,980 (64.5%) with CCD; 10,938 (22.7%), with non-elevated ST segments and unstable angina; and 6,185 (12.8%), with AMI. RESULTS: Diabetic patients presented worse clinical and angiographic characteristics. Diabetics with CCD showed similar incidence of MACE as compared to non-diabetics (0.98% x 0.91%, p=0.5971); however, diabetics with ACSNST and AMI reported higher incidence of events: 2.76% x 1.46% (p<0.0001) and 7.87% x 4.1% (p<0.0001), respectively. Multivariate analysis showed DM to act as independent risk predictor for larger adverse events under non-elevated ST segment and unstable angina (ACSNST) (OR: 1.92 CI: 1.46-2.52 p<0.0001) and with AMI (OR: 2.0 CI: 1.57-2.54 p<=0.0001) and no influence for CCD (OR: 1.08 CI: 0.83-1.42 p=0.5470 CONCLUSION: Diabetic patients with CCD reported similar outcome as compared to the non-diabetics; however, those with ACSNST and AMI presented higher incidence of major adverse cardiac events during hospital stay.
Diabetes Mellitusstentingcoronary atherosclerosis
ORIGINAL ARTICLE
Influence of diabetes mellitus on immediate results of coronary stent: national center for cardiovascular interventions (CENIC) data analysis
Isaac Moscoso; Lázaro Claudiovino Garcia; Gilvan Oliveira Dourado; Maria Fernanda Z. Mauro; Paulo Caramori; Wilson Coelho; Valter Lima; Ronaldo Bueno; José A. Mangione
CENIC - Central Nacional de Intervenções Cardiovasculares da Sociedade Brasileira de Hemodinâmica e Cardiologia Intervencionista - São Paulo, SP - Brazil
Mailing Address
ABSTRACT
OBJECTIVE: This study sought to investigate the influence of Diabetes Mellitus (DM) on immediate results after coronary stenting implantation (CSI) according to clinical presentation.
METHODS: Between January, 1997 and December, 2003, 11,874 diabetic patients underwent CSI, as recorded by CENIC database: 7,386 (62.3%) had chronic coronary disease (CCD); 3,142 (26.4%) acute coronary syndrome with non-ST segment elevation (ACSNST); and 1,346 (11.3%), reported acute myocardial infarction (AMI), with ST Segment elevation. Those groups were compared with 48,103 non-diabetics: 30,980 (64.5%) with CCD; 10,938 (22.7%), with non-elevated ST segments and unstable angina; and 6,185 (12.8%), with AMI.
RESULTS: Diabetic patients presented worse clinical and angiographic characteristics. Diabetics with CCD showed similar incidence of MACE as compared to non-diabetics (0.98% x 0.91%, p=0.5971); however, diabetics with ACSNST and AMI reported higher incidence of events: 2.76% x 1.46% (p<0.0001) and 7.87% x 4.1% (p<0.0001), respectively. Multivariate analysis showed DM to act as independent risk predictor for larger adverse events under non-elevated ST segment and unstable angina (ACSNST) (OR: 1.92 CI: 1.46-2.52 p<0.0001) and with AMI (OR: 2.0 CI: 1.57-2.54 p<=0.0001) and no influence for CCD (OR: 1.08 CI: 0.83-1.42 p=0.5470
CONCLUSION: Diabetic patients with CCD reported similar outcome as compared to the non-diabetics; however, those with ACSNST and AMI presented higher incidence of major adverse cardiac events during hospital stay.
DM prevalence has increased progressively in the last 20 years. One hundred million people worldwide are estimated to be DM carriers in our days1. DM is an important risk factor for general atherosclerosis. Therefore, cardiovascular complications are the major causes for death and impairment in those patients2. Additionally, diabetics exhibit a more aggressive course for coronary diseases, which results in 45% death incidence within 7 years, and 75% within 10 years after the onset of symptoms3.
In diabetics, immediate and long-term results following percutaneous coronary intervention (PCI) used to be unfavorable when compared to non-diabetics4,5. However, results have improved after the use of coronary stenting6 associated to aspirin anti-platelet-aggregation therapy, thienopyridine derivates, and glycoprotein IIb/IIIa receptor inhibitors7,8. However, the benefit of such association for the diabetic population is still controversial9.
The clinical presentation of coronary disease is important for short and long term prognostics in diabetic patients. Those reporting acute conditions are exposed to higher risk of death and non-fatal infarction10 during hospital stay; and those with stable angina have reported shorter survival time during long-term outcome11 when compared to the non-diabetics. Age and gender have been the basis for comparison between those two populations for most studies using PCI as treatment procedure; however, few studies have analyzed the clinical presentations. Except for AMI, most series publications on percutaneous treatment in diabetics have associated presentation clinical condition (stable and unstable angina); few studies have analyzed whether clinical presentation of coronary diseases influence immediate results for percutaneous treatment in diabetics.
The purpose of this study was to compare the immediate results of coronary stenting between diabetic and non-diabetic patients based on clinical condition.
METHODS
Records of patients submitted to coronary stenting between January, 1997, and December, 2003 at CENIC – which belongs to the Brazilian Society of Hemodynamic and Interventional Cardiology (SBHCI) – were analyzed. Data collection stored in a database was the spontaneous contribution of permanent members. Patients submitted to balloon angioplasty only were excluded from the analysis, since results are suboptimal when compared to stenting, in addition to being a procedure not widely used in the most recent years.
In the first analysis, patients were divided into diabetics (DM) and non-diabetics (N-DM): clinical and angiographic data, as well as immediate post-procedure results were compared. Patients were later divided into three groups according to clinical presentation: chronic coronary disease (CCD), defined as stable angina, silent ischemia, recent onset and progressive angina; moderate and high risk non-elevated ST segment, following TIMI Risk Score12 and non-Q-wave AMI (ACSNST); and acute myocardial infarction (AMI), defined as AMI with supra-unlevelling of ST segment, submitted to primary angioplasty. Results from diabetics and non-diabetics were compared in the groups.
Study primary outcome was to investigate the incidence of a combined event: death, AMI, and the need for surgical or percutaneous revascularization during hospital stay. Death was defined as the outcome from any etiology; acute myocardial infarction (AMI), as the elevation of CK-MB > 3 times normal value13 and/or development of electrocardiographic changes following Novacode criteria14 (Minnetosa code extension). In AMI patients, infarction was defined as the re-elevation of CK-MB13 levels.
Statistical analysis was carried out through Statistica for Windows, Version 5.0 (StatSoft Inc. Tulsa, Oklahoma, USA). Categorical variables were percentually expressed and compared through Pearson’s chi-square. Continuous variables were expressed as mean ± SD and analyzed through Student t test. p<0.05 was considered statistically significant. A multivariate analysis was then carried out to calculate DM odds ratio in primary end-point components: death, AMI, need for revascularization (surgical or percutaneous), combination of death/AMI (irreversible events), and total events in the group as a whole and for each clinical condition.
RESULTS
Between January, 1997 and December, 2003 CENIC database showed 59,977 patients had been submitted to coronary stenting. From those, 11,874 (19.8%) were diabetics and 48,103 (80.2%), non-diabetics. Clinical and angiographic data can be found in Table 1. Diabetic patients reported a higher number of female patients, higher incidence of previous surgical revascularization, previous coronary angioplasty, severe left ventricle dysfunction, tri-arterial coronary disease, complex coronary lesions (type C, intracoronary thrombus, calcification, bifurcation), saphenous vein graft lesions, and more frequent use of GP IIb/IIIa inhibitors (p<0.05 for all comparisons).
Angiographic success rate was lower in the DM group (98.5%) x non-DM (98.8%) (p=0.8244), with higher post-procedure diameter stenosis: 8.89 ± 11.46 x 7.66 ± 10.56 (p<0.0001). Primary outcome occurred in the DM group (2.23%) x non-DM (1.44%) (p<0.0001). As for primary outcome components, incidence of death was higher (1.24% x 0.73%, p<0.0001), new PCI (0.28% x 0.15%, p=0.0355), and a trend towards a higher rate of AMI (0.61% x 0.48%, p=0.0835) in the diabetic population. No difference was shown by the groups regarding the need for surgical revascularization (0.08% x 0.07%, p=0.7655) (Fig. 1).
SUBGROUPS ANALYSIS
CCD -Among CCD patients (n = 38,366), 7,386 (19.2%) were diabetics and also reported unfavorable clinical and angiographic condition (Table 2), such as: age, females, previous myocardial revascularization (MR) and PCI, triarterial disease, severe dysfunction of LV, C lesions, calcification, bifurcation, and higher use of abciximab (p<0.05 for all comparisons). In regard to treated vessels, higher incidence of saphenous vein graft (2.3% x 1.6%, p<0.0001) and lower incidence of intervention in LAD (42.2% x 44.1%, p=0.0399) were reported.
Angiographic success rate was similar for DM (98.8%) x non-DM (98.8%) (p=0.8555) patients. Primary end-point occurred in 0.98% in DM x 0.91% in non-DM (p= 0.5971). No difference was reported related to incidence of death (0.26% x 0.29%, p=0.7532), AMI (0.41% x 0.41%, p=0.9241), or the need for surgical revascularization (0.05% x 0.07%; p=0.8017). However, the DM group reported higher need for a new PCI (0.26% x 0.14%, p=0.0284) (Fig. 2).
ACSNST - From patients with non ST elevation segment (n = 14,080), 3,142 (22.3%) were diabetics; similarly to the CCD group, those patients reported unfavorable clinical and angiographic data (Table III), such as: age, females, previous MR and PCI, triarterial disease, severe dysfunction of LV, intracoronary thrombus, bifurcation lesion, and higher use of abciximab (p<0.05). As for vessels treated, higher incidence of saphenous vein graft intervention (3.8% x 3.1%, p=0.0349), as well as lower incidence of anterior descending artery (AD) intervention (41.4% x 44.3%, p=0.0007) were reported.
Angiographic success rate was similar for DM (98.8%) x non-DM (98.8%) (p=0.7757) patients. Primary end-point was reported 2,76% in DM patients x 1.46% in non-DM (p<0.0001). Higher rate of death was reported in the DM group (1.50% x 0.64%, p<0.0001). However, no difference was observed related to AMI (0.83% x 0.59%, p=0.1931), or the need for surgical (0.13% x 0.07%; p=0.5691) or percutaneous (0.32% x 0.16%, p=0.1088) revascularization. (Fig. 3).
AMI - was presented in 7,531 patients (12.5%). From those, 1,346 (17.8%) were diabetics. Clinical and angiographic data can be found in Table 4. Diabetic patients reported more unfavorable clinical and angiographic data (age, female gender, previous MR and PCI, triarterial disease, cardiogenic shock, calcified lesions; p<0.05), as well as higher saphenous vein graft intervention (p<0.0001).
Angiographic success rate was lower for DM (97.6%) x non-DM (98.5%) (p=0.0244) patients. In this population, primary end-point was reported in 7.87% of DM patients x 4.1% in non-DM. (p= 0.0001). Incidence of death was higher (6.09% x 3.12%, p=0.001) as was reinfarction rate (1.26% x 0.68%, p=0.0444), with no difference in the need for surgical (0.15% x 0.06%; p=0.903) or percutaneous (0.37% x 0.24%, p=0.5903) revascularization. (Fig. 4).
MULTIVARIATE ANALYSIS
Multivariate analysis can be found in Table 5. DM showed to be an independent risk predictor for death in the group as a whole. (OR 1.71 CI: 1.40 – 2.09; p<0.0001), AMI (OR 1.27 CI: 0.97 – 1.67; p<p=0.0740), new revascularization (OR 1.65 CI: 1,15 – 2.38; p=0.0045), as well as death/AMI (OR 1.59 CI: 1.36 – 1.86; p<0.0001).
In the CCD group, DM did not show to be a predicting factor for adverse events (p>0.05 for all assessments).
In the ACSNST group, DM also showed to be an independent risk predictor for death (OR 2.36 CI: 1.60 – 3.47; p<0.0001), new revascularization (OR 1.95 CI: 0.96 – 3.92; p=0.0410), and death/AMI (OR 1.90 CI: 1.41- 2.56; p<0.0001).
In the AMI group, DM was an independent predictor for death (OR 2.01 CI: 1.53 – 2.65; p<0.0001), AMI (OR 1.87 CI: 1.02 – 3.40; p=0.0276), and death/AMI (OR 2.01 CI: 1,57 – 2.58; p<0.0001).
DISCUSSION
Based on our data, DM showed to cause adverse effects in coronary stenting immediate results when compared to the non-DM group. Such results are similar to those recently published in the literature9,15-17. As in all of these series, diabetic patients reported unfavorable clinical and angiographic data. It is important to point out that in spite of that, the use of coronary stents brought similar angiographic success to the groups. However, after the procedure, the angiographic analysis of diabetic patients showed higher grade of stenosis, which is associated to the increase of post-PCI restenosis, although not yet defined as a predictor for immediate adverse events.
Although diabetic patients have used GP IIb/IIIa inhibitors more often as compared to non-diabetics (10.6% x 7.6%, p<0.0001), such rate is lower than other series published in literature. Mathew16 et al have reported the use of IIb/IIIa inhibitor in 25% of the 2,694 treated diabetics in the PRESTO study. Walton et al18, in their turn, used it in 38% of the 707 treated diabetic patients at a community hospital in Washington DC. The benefit of IIb/IIIa inhibitors in diabetics has been demonstrated by randomized trials7,8,19 as well as by non-randomized series 18,20,21. The inhibitors might have had favorable action if used in a wider number of patients in this series.
Another important aspect to be pointed out is the higher incidence of venous surgical grafts in those patients. In the opinion of Ahmed et al22, mortality rate is higher among diabetics who have been submitted to saphenous vein graft stenting, which does not favor hospital evolution for those patients. It is likely that the use of protection systems – to avoid distal embolization - may improve those results if used as routine procedure in this population.
DIABETES AND CCD
To this point in time, it is still not clear whether myocardial revascularization - as early treatment strategy - is beneficial for diabetics with chronic coronary disease23, except for multiarterial coronary disease patients (3 vessels and 2 vessels disease), with proximal AD portion commitment), left coronary main lesion, and significant ventricular dysfunction24. The use of stenting in percutaneous revascularization procedures seems to have neutralized diabetics’ excessive risk level when submitted to conventional balloon angioplasty. Some difference can still be found, though, when compared to non-diabetics.
Diabetes has not shown to be a risk factor in post-PCI immediate results in CENIC database analysis. Our results agree with those by Abizaid et al25, who have analyzed randomized patients in the stent subgroup of the ARTS study and have found no difference in the incidence level of adverse events in the hospital phase of diabetic patients (in that study, approximately 60% of the patients reported stable angina/ silent ischemia). While analyzing 386 patients who had been submitted to coronary stenting, Bayerl et al26, in their turn, did not demonstrate any mortality rate increase among diabetic patients, although increased incidence of post-procedure AMI (7.4% x 1.9%, p=0.022) was reported, most likely due to distal microembolization as a result of higher atherosclerotic plaque burden – a characteristic in those patients27.
The use of GP IIb/IIIa inhibitors does not seem to influence results of stable ischemic syndrome (stable angina/silent ischemia) in this group of patients, as demonstrated by Lima et al28 Neither have Chaves et al29, in the DANTE study, demonstrated any benefit from the use of abciximab in immediate results, or in the reduction of neointimal hyperplasia six months after stent implantation in diabetic patients. In the present study, only 23% of patients reported unstable angina. Finally, Kastrati et al30 have not found any benefit in using abciximab when comparing to a 600 mg attack dose of clopidogrel in the subgroup of diabetic patients with chronic coronary disease who have been submitted to stent implantation. The analysis of those results suggests that the use of GP IIb/IIIa inhibitors in this group of patients is not to be based on DM condition only.
Diabetes and SCANST: This group of patients has benefited from early interventional procedure associated to the use of GP IIb/IIIa inhibitors if compared to clinical treatment31. DM causes changes in the coagulation system that favor thrombosis and decrease fibrinolysis, thus increasing the risk of death and non-fatal AMI.
Diabetes and ACSNST
Our results have shown that diabetic patients are also exposed to higher risk of adverse events when submitted to percutaneous intervention, similarly to other published series. While analyzing 279 patients with unstable angina who had been submitted to PCI, López-Minguez et al32 found higher mortality rate and non-fatal AMI among diabetic patients in a 3-year clinical follow-up( 11.6% x 4.6%, p=0.047). A post-hoc analysis of OASIS registry – carried out by Malmbert et al33 – also found a 57% increase in the mortality rate of SCANST diabetic patients.
Although diabetics in our series have reported adverse clinical and angiographic profile, another factor that may have influenced unfavorable results was low use of GP IIb/IIIA inhibitors (11.9%), as compared to other non-randomized series, as that of López-Minguez, when abciximab was used for 47.8% of diabetic patients. The use of coronary stenting and of the GP IIb/IIIa inhibitor tirofiban in the TACTICS31 study, and the in the recently published SYNERGY34 was associated to significant risk reduction in diabetics with SCANST submitted to percutaneous intervention.
In our study, diabetes and AMI patients showed worse immediate results, in agreement with other published series in the literature. Silva et al35 have analyzed 104 patients submitted to primary stenting. In that study, diabetics reported higher MACE incidence on day 30 (21% x 4%, p=0.009), particularly sub-acute thrombosis (18% x 1%, p=0.003). Harjai et al36 have analyzed the results of 626 diabetic patients from the PAMI study database, having related no difference in the multivariate analysis in hospital death rate, although difference was found in mortality rate level at month 6. (OR 1.53 - IC95%: 1.03-2.26, p=0.03). While analyzing a total of 4,308 patients submitted to primary PTCA in the course of a 20-year period, Marso et al16 also observed diabetes to be associated to higher hospital death rate (12.7% x 6.9%, p<0.001) – which was kept high at all time points in the analysis.
The use of stenting and GP IIb/IIIa inhibitors has also improved the results of primary PTCA in diabetic patients. In the ADMIRAL37 study, the use of abciximab in patients who had been submitted to AMI stenting was associated to relative risk reduction (67%) in diabetic patients. In the CADILLAC38 study, the reduction showed to be 44%. The future may see new forms of AMI percutaneous intervention (thrombectomy systems, distal protection, supersaturated liquid oxygen, and systemic hypothermia) to further improve the results for these patients.
Multivariate Analysis
Our results agree with those previously published regarding diabetes and percutaneous coronary intervention in current practice. While analyzing 100,253 procedures in the ACC-NCDR database, Shaw et al39 found Diabetes Mellitus to be an independent predictor of death in the hospital phase (OR: 1.41 CI: 1.10-1.91 p<0.0001). However, no analyses were carried out based on clinical presentation. In our study, however, the multivariate analysis did not show higher risk for diabetic patients - carriers of chronic coronary disease – who have been submitted to percutaneous coronary intervention. Such information had not yet been reported in world literature.
Limitations
The present work has some limitations, since it is a retrospective analysis. Additionally, considering it is a national registry, differences in routines and procedures may exist between the different cardiology interventional services participating in CENIC registry. In spite of that, it does reflect the current practice for percutaneous coronary intervention in our country. Another limitation the study faces is lack of follow-up data on treated patients. CENIC database only stores immediate results from percutaneous procedures, which allows safety and efficacy assessment during hospital stay. However, no data are available on patients’ follow-up, which in our view is crucial for better assessment of the results for the treatment of diabetic patients.
CONCLUSIONS
The study concludes that Diabetes Mellitus is still an independent risk factor for patients who have been submitted to percutaneous coronary intervention in current practice. In the lower risk group, however, such scenario is being reverted by the use of coronary stenting associated to pharmacological therapeutics.
The results of new treatment strategies are to be awaited: drug-eluting stents, protection devices, and new anti-thrombotic drugs associated to strict metabolic and risk factors control as part of Diabetes Mellitus multidisciplinary management.
Acknowledgments
SBHCI permanent members who participated in the CENIC national registry are listed below: Abdu Neme Jorge Makhluf Neto, Ademar Santos Filho, Adnan Ali Salman, Adriano Mendes Caixeta, Adriano Dias Dourado Oliveira, Adriano Mendes Caixeta, Alcides Jose Zago, Aldegyo Volney da Terra Caldeira, Aldo Fernando Somavilla Duarte, Alex D’Albuquerque Silva, Alexandre Antonio Cunha Abizaid, Alexandre Damiani Azmus, Alexandre do Canto Zago, Alexandre do Canto Zago, Alexandre Manoel Varela, Alexandre Schaan Quadros, Aluisio Cruz Junior, André Labrunie, Anellys Emilia Lourenco da Costa Moreira, Angelo Amato Vicenzo de Paola, Angelo Leone Tedeschi, Anselmo Antonio Salgado, Antenor Lages Fortes Portela, Antenorio Aiolfi, Antonio Carlos Neves Ferreira, Antonio Esteves Filho, Antonio Gilson Lapa Godinho, Antonio Jose Muniz, Antonio Luiz Secches, Antonio Moraes de Azevedo Junior, Ari Mandil, Augusto Lima Filho, Boris Ivan Cosquillo Mejia, Caio Mario de Almeida Pessoa, Carlos Antonio Alzamora Zapata, Carlos Antonio Mascia Gottschall, Carlos Augusto Formiga Áreas, Carlos Eduardo Diniz Couto, Carlos Roberto Cardoso, Celmo Ferreira de Souza Junior, Cesar Augusto Esteves, Cesar Rocha Medeiros, Charles Luiz Vieira, Clacir Staudt Marin Sojo, Claudia Maria Rodrigues Alves, Claudia Mattos, Claudio Antonio Ramos Moraes, Clemente Greguolo, Costantino Roberto Frack Costantini, Cyro Vargues Rodrigues, Decio Salvadori Junior, Dinaldo Cavalcanti de Oliveira, Ederval Key Hayashi, Edgar Guimaraes Victor, Edie Mello de Oliveira, Edison Carvalho Sandoval Peixoto, Edmundo André Viveiros Pessanha, Edmur Carlos de Araújo, Edson Ademir Bocchi, Eduardo Arantes Nogueira, Elias de Mello Ayres Neto, Ernaldo Vagner Goncalves Pardi, Eulogio Emilio Martinez Filho, Expedito E. Ribeiro da Silva, Fábio Sândoli de Brito Jr, Fausto Feres, Fernando Mendes Sant Anna, Fernando Stuchi Devito, Flavio Celso Leboute, Flavio José Rocha de Souza, Francisco Cabral Cardoso, Francisco de Assis Costa, Francisco de Paula Stella, Galo Alfredo Maldonado Andrade, George Cesar Ximenes Meirelles, Geraldo Luiz de Figueiredo, Gilberto Guilherme Ajjar Marchiori, Gilberto Lahorgue Nunes, Gilvan Oliveira Dourado, Gonzalo Moises Herrera Mejia, Gustavo de Moraes Ramalho, Gustavo Enrique Sanches Alvarez, Heitor Ghissoni de Carvalho, Helio José Castello Jr, Helman Campos Martins, Heloisa Maria Melo Silva Guimarães, Itamar Ribeiro de Oliveira, Jamil Abdalla Saad, Jamil da Silva Soares, João Batista de Freitas Guimarães, João Batista de Oliveira Neto, João Batista Lopes Loures, João Lourenco Villari Herrmann, João Oravio de Freitas Jr, João Otavio Queiroz F. Araújo, Joao Paulo Zouvi, Jorge de Camargo Neto, Jorge Hideki Hayashi, José Antonio Jatene, José Antonio Marin Neto, José Armando Mangione, José Augusto Marcondes de Souza, José Augusto Rocha Araújo, José Carlos Raimundo Brito, José Domingos de Almeida, José Eduardo Morais Rego Sousa, José Guilherme Carneiro, José Klauber Roger Carneiro, José Luis Attab dos Santos, José Marconi Almeida de Souza, José Maria Dias de Azeredo Bastos, José Mariani Jr, José Walter Mendes Nogueira, Julio Vinicius de Souza Teixeira, La Hore Correa Rodrigues, Lazaro Claudovino Garcia, Leonardo Alves Batista, Leonardo Cogo Beck, Leonidas Alvarenga Henriques, Leopoldo Eduardo San Martin Gómez, Leslie Albuquerque Aloan, Luciano Mauricio de Abreu Filho, Luciano Nogueira Liberato de Sousa, Luis Maria Cabrera Yordi, Luiz Alberto Piva E Mattos, Luiz Alberto Rolla Maneschy, Luiz Antonio Gubolino, Luiz Antonio Pechiori Finzi, Luiz Junya Kajita, Maeve de Barros Correia, Manoel Augusto Baptista Esteves, Manuel Nicolas Cano, Marcelo Antonio Cartaxo Queiroga Lopes, Marcelo Augustus Sena, Marcelo de Freitas Santos, Marcelo José de Carvalho Cantarelli, Marcelo Lemos Ribeiro, Marcio Mesquita Barbosa, Marco Antonio Perin, Marcos Antonio Marino, Marcos de Oliveira Gusmão, Marcus Nogueira da Gama, Maria Cristina Meira Ferreira, Mario Salles Netto, Maurício Lopes Prudente, Mauro Jose Mello Fonseca, Miguel Antonio Neves Rati, Milton de Macedo Soares Neto, Moacyr Fernandes de Godoy, Moyses de Oliveira Lima Filho, Murillo Kenji Furukawa, Nelson Antonio Moura de Araújo, Nilson Borges Ramos, Nilson de Moura Fe Filho, Nilton Carlos Spinola Machado, Norberto Toazza Duda, Noriaki Takeshita, Paulo Bezerra de Araujo Galvão, Paulo Ricardo Avancini Caramori, Paulo Sergio de Oliveira, Pedro Abilio Ribeiro Reseck, Pedro Augusto Pascoli, Pedro Eduardo Horta, Pedro Esberard de Aragão Beltrão, Pierre Labrunie, Raimundo Antonio de Melo, Raimundo João Costa Furtado, Raul D’Aurea Mora Junior, Ricardo Lasevitch, Ricardo Pontes Miranda, Roberto de Almeida César, Roberto Otsubo, Roberto Silveira Pinna, Rodolfo Alberto Silveira Malta Alencar, Rodolfo Staico, Rogério de Castro Pimentel, Rogério Eduardo Gomes Sarmento Leite, Ronaldo de Amorim Villela, Ronei Bosco Matos, Rosaly Gonçalves, Rubens Zenobio Darwich, Salvador Andre Bavaresco Cristóvão, Sérgio Luis Berti, Sérgio Luiz Navarro Braga, Sérgio Martins Leandro, Silvio Giopatto, Trajano Alfonso, Ulises Enrique Acuña Solórzano, Valerio Fuks, Valter Correia de Lima, Vasco Morosini Miller, Walasse Rocha Vieira, Waldir Gomes Malheiros, Walkimar Ururay Gloria Veloso, Wesley Ferraz da Silveira, Wilson Albino Pimentel Filho, Wilson Alfaia de Oliveira, Wilson Miguel Cecim Coelho.