Enxerto de Bypass de Artéria Coronária Guiado por Angiografia ou Fisiologia: Uma Metanálise

José Martins; Vera Afreixo; Luís Santos; Luís Fernandes; Ana Briosa

doi:10.36660/abc.20200763

. 2021 Nov 22;117(6):1115–1123. [Article in Portuguese] doi: 10.36660/abc.20200763

View full-text in English

Enxerto de Bypass de Artéria Coronária Guiado por Angiografia ou Fisiologia: Uma Metanálise

José Martins ^1,^✉, Vera Afreixo ², Luís Santos ¹, Luís Fernandes ³, Ana Briosa ¹

PMCID: PMC8757150 PMID: 35613169

Resumo

Fundamento:

Enquanto a angiografia coronária invasiva é considerada padrão outro para o diagnóstico da doença arterial coronariana (DAC), envolvendo os vasos coronários epicárdicos, a revascularização coronariana guiada por fisiologia representa uma prática padrão ouro contemporânea para a administração invasiva de pacientes com DAC intermediária. Porém, os resultados de longo prazo da avaliação da gravidade da estenose por meio da fisiologia, em comparação à angiografia como guia para a cirurgia de bypass – enxerto de bypass de artéria coronária (CABG), ainda são incertos. Esta metanálise visa avaliar os resultados clínicos de um CABG guiado por fisiologia em comparação a um CABG guiado pela angiografia.

Objetivos:

Buscamos determinar se os resultados entre um CABG guiado por fisiologia e os de um CABG guiado por angiografia são diferentes entre si.

Métodos:

Pesquisamos nas bases Medline, EMBASE e Cochrane Library. A última data de busca foi junho de 2020, e todos os estudos anteriores foram incluídos. Realizamos uma metanálise de razão de risco agrupado para quatro principais resultados: morte por todas as causas, infarto do miocárdio (IM), revascularização do vaso alvo (TVR) e eventos cardiovasculares adversos maiores (MACE). Valor de p <0,05 foi considerado estatisticamente significante. A heterogeneidade foi avaliada com o teste Q de Cochran, e quantificada pelo índice I2.

Resultados:

Identificamos cinco estudos incluindo um total de 1.114 pacientes. Uma metanálise agrupada não demonstrou diferenças significativas entre a estratégia da fisiologia e da angiografia para IM (razão de risco [RR] = 0,72; IC95%, 0,39–1,33; I2 = 0%; p = 0,65), TVR (RR = 1,25; IC95% = 0,73–2,13; I2 = 0%; p = 0,52), ou MACE (RR = 0,81; IC95% = 0,62–1,07; I2 = 0%; p = 1). A estratégia da fisiologia apresentou 0,63 vezes o risco de morte por todas as causas em comparação à estratégia da angiografia (RR = 0,63; IC95% = 0,42–0,96; I2 = 0%; p = 0,55).

Conclusão:

Esta metanálise demonstrou uma redução nas mortes por todas as causas quando usada a estratégia do CABG guiado por fisiologia. Porém, o curto período de acompanhamento, o tamanho da amostra pequeno dos estudos incluídos e a não-discriminação das causas de morte podem justificar essas conclusões. Estudos com períodos mais longos de acompanhamento são necessários para tirar conclusões mais robustas e definitivas.

Palavras-chave: Doença da Artéria Coronariana, Angiografia, Metanálise, Artéria Coronária/fisiologia, Angiografia Coronária, Ponte de Artéria Coronária

Introdução

A angiografia coronária invasiva é considerada padrão ouro para o diagnóstico da doença arterial coronariana (DAC) envolvendo os vasos coronários epicárdicos.¹ Porém, a avaliação visual por meio da angiografia coronária tradicional não é capaz de distinguir se uma estenose coronária é hemodinamicamente significativa, principalmente na DAC intermediária; então, há discordâncias constantes entre a gravidade angiográfica e a significância da fisiologia na DAC.^2,3 As discrepâncias ocorrem porque, diferentemente da angiografia, a fisiologia incorpora os efeitos combinados e inter-relacionados do fluxo coronário e da resistência microvascular.³

Há crescentes evidências que apoiam os benefícios clínicos e a custo-efetividade da revascularização coronária percutânea guiada pela fisiologia, seja pelos índices baseados na hiperemia ou pelos índices baseados na diferença de pressão durante um período específico da diástole, em comparação à revascularização percutânea baseada na angiografia coronária.^4-7 Porém, os resultados de longo prazo da avaliação da gravidade da estenose por meio da fisiologia, em comparação à angiografia como guia para a cirurgia de bypass, ainda são incertos.

Considerando esses resultados, cirurgiões cardíacos estão progressivamente guiando a revascularização da doença de múltiplos vasos (MVD) com base na fisiologia coronária. Porém, ainda não está claro se esta decisão traz melhores resultados clínicos de longo prazo. As recomendações sobre o uso do CABG em comparação à terapia médica ou à intervenção coronária percutânea (ICP) são inteiramente baseadas em estudos que utilizam critérios anatômicos e não-funcionais para guiar a revascularização.^8-12

Por conta desses dados, muitos autores já avaliaram o potencial benefício clínico da cirurgia de bypass da artéria coronária guiada pela fisiologia, além dos detalhes anatômicos para decisões cirúrgicas.^13-20 Neste artigo, estendemos o trabalho de Spadaccio et al.,²⁰ ao agrupar todos os resultados de estudos randomizados e não-randomizados para avaliar o efeito nos resultados clínicos entre o CABG guiado por fisiologia em comparação ao CABG guiado pela angiografia.²⁰

Métodos

Fontes de dados e buscas

Nós fizemos buscas sistemáticas nas bases Medline, Embase e Cochrane Library, pesquisando artigos publicados relevantes. A última data da busca foi em junho de 2020, e todos os estudos anteriores foram incluídos na busca. Revisões sistemáticas e qualitativas prévias, se disponíveis, foram consideradas para estudos adicionais. Os seguintes termos de busca foram utilizados: “Fisiologia coronária” ou “Fluxo Fracionado de Reserva” ou “FFR” ou “Instant Wave-Free Ratio” ou “iFR” ou “Enxerto de bypass de artéria coronária” ou “CABG”. Outros estudos foram buscados por pesquisa manual ou em fontes secundárias, incluindo referências de artigos primários. Não houve restrições de língua na busca.

Seleção dos estudos

As citações foram primeiramente selecionadas pelo título/resumo por dois revisores independentes (JM e LS), e os manuscritos completos foram avaliados se fossem potencialmente pertinentes. Discordâncias foram resolvidas após chegarem a um consenso. Os artigos identificados foram avaliados pelos mesmos revisores, de acordo com os seguintes critérios de inclusão: artigos com resultados clínicos comparando as duas estratégias para a revascularização no CABG (fisiologia versus angiografia). As disputas relacionadas aos critérios de inclusão foram resolvidas até chegarem a um consenso. Estudos comparando ambas as estratégias que não reportaram os resultados clínicos foram excluídos. Os estudos que não reportaram a estratégia usada em detalhe, embora tivessem a avaliação dos resultados clínicos, também foram excluídos (Figura 1).

Desfechos

Os desfechos estudados foram: morte por todas as causas, infarto do miocárdio (IM), revascularização do vaso alvo (TVR) e eventos cardiovasculares adversos maiores (MACE) durante o período de acompanhamento.

MACE foi definido como um composto de morte, infarto do miocárdio ou qualquer revascularização de Moscona et al.,¹⁶ Fournier et al;¹⁸ e como um composto de morte, infarto do miocárdio, derrame ou qualquer revascularização dos estudos FARGO, FUTURE e GRAFFITI durante o período de acompanhamento.^13-19

Análise estatística

Para calcular as estimativas do efeito agrupado, utilizamos a variância inversa assumindo um modelo de efeito fixo, e o método de DerSimonian e Lard²¹ assumindo o modelo do efeito randômico.²¹ A homogeneidade entre os estudos foi avaliada com o teste Q de Cochrane e o índice I2 (os valores de 0,25, 0,50 e 0,75 indicaram níveis baixos, moderados e altos de heterogeneidade, respectivamente). O valor de p <0,05 foi considerado estatisticamente significativo. O viés de publicação foi avaliado utilizando o gráfico em funil. Realizamos uma análise de sensibilidade para mostrar o impacto de cada estudo nos resultados. O MetaXL 2.0 (EpiGear International Pty Ltd, Wilston, Queensland, Australia) foi usado para calcular o tamanho do efeito da diferença do risco agrupado (diferença entre o risco dos grupos com revascularização e com gerenciamento conservador).

Resultados

Identificação do Estudo

As buscas nas bases de dados inicialmente encontraram 372 citações. Dessas, seis estudos duplicados e 321 artigos foram excluídos após a revisão do título ou resumo. Depois de uma avaliação aprofundada de acordo com os critérios de seleção, excluímos mais 40 estudos. Um final total de cinco estudos foi incluído na análise. Esses cinco estudos incluíam 1.114 pacientes: 403 no grupo guiado pela fisiologia, e 711 no grupo guiado pela angiografia.

Características dos estudos incluídos

Dos cinco estudos incluídos, três eram randomizados e dois eram não-randomizados, observacionais e retrospectivos (Tabelas 1 e 2)

Tabela 1. Características dos estudos incluídos.

Autor	Ano	N total	N - estratégia	Acompanhamento	Desenho do estudo	Vias	Oclusão do enxerto - acompanhamento	Principais conclusões clínicas
Moscona et al.¹⁶	2018	109	Guiado por FFR/iFR-: 14 Guiado por angiografia: 95	18 meses	Retrospectivo	Via arterial: 92,9% (grupo FFR; 90,5% Grupo angiografia) EVS: 85,7% (grupo FFR;76,8%; grupo angiografia)	NR	Uma tendência de redução da MACE (7,1% vs. 11,6%, P=0,369) e angina (0,0% vs. 6,3%, P=0,429) no grupo FFR/iFR em comparação ao grupo da angiografia.
Thuesen et al.¹⁴	2018	97	Guiado por FFR: 49 Guiado por angiografia: 48	Seis meses	Estudo controlado randomizado	Via arterial: 37%	Falência de enxerto de todos os enxertos foi similar em ambos os grupos (16% vs. 12%; p = 0,97).	Taxas de morte, IM, e derrame foram similares nos grupos do estudo. A mortalidade por todas as causas após seis meses foi de 0% no grupo FFR, e 4,1% no grupo angiografia; um paciente morreu por conta de embolia pulmonar, e um morreu de mediastinite.
Rioufol et al.¹⁷	2018	109	Guiado por FFR: 55 Guiado por angiografia: 54	Um ano	Estudo randomizado controlado	NR	NR	FFR em pacientes com doença de múltiplos vasos não demonstrou melhora no desfecho do composto primário de mortalidade por todas as causas, IM, revascularização repetida ou derrame por um ano (14,6% vs 14,4%; HR 0,97; IC95% 0,69-1,36) Risco de morte foi significativamente maior no grupo FFR (3,7% vs 1,5%; P = 0,036)
Fournier et al.¹⁵	2019	627	Guiado por FFR: 198 Guiado por angiografia: 429	Seis anos	Retrospectivo	Via arterial: 64% EVS: 36%	A taxa de oclusão foi significativamente mais baixa no grupo FFR em comparação ao da angiografia	CABG guiado por FFR está associado à redução significative na taxa de morte geral ou infarto do miocárdio (HR 0,59 [IC95%, 0,38–0,93]; P=0,020)
Toth et al.¹⁹	2019	172	Guiado por FFR: 88 Guiado por angiografia: 84	Um ano	Estudo randomizado controlado	NR Taxa da Via arterial-para-EVS: 1:1	Não houve diferença na oclusão geral dos enxertos (80% vs 81%) p=0,885)	Não houve diferença no composto morte, infarto do miocárdio, vaso algo, revascularização e derrame (HR 1,275; IC95%: 0,391 a 4,160, p=0,674)

Open in a new tab

FFR: Fluxo fracionado de reserva; iFR: proporção instantânea de ondas livres; N: pacientes incluídos no estudo; IM: infarto do miocárdio; TVR: revascularização do vaso alvo; NR: não reportado; EVS: enxerto de veia safena; CABG: enxerto de bypass de artéria coronária. Valor de p < 0,05 foi considerado significativo em todos os estudos incluídos.

Tabela 2. Características dos estudos incluídos.

Autor	Ano	N total	N - estratégia	Morte	IM	TVR	MACE
Moscona et al.¹⁶	2018	109	Guiado por FFR/iFR: 14 Guiado por angiografia: 95	FFR/iFR: 1 Angiografia: 5	FFR/iFR: 0 Angiografia: 2	FFR/iFR: 0 Angiografia: 4	FFR/iFR: 1 Angiografia: 11
Thuesen et al.¹⁴	2018	97	Guiado por FFR: 49 Guiado por angiografia: 48	FFR: 0 Angiografia: 2	FFR: 1 Angiografia: 0	FFR: 2 Angiografia: 0	FFR: 6 Angiografia: 6
Rioufol et al.¹⁷	2018	109	Guiado por FFR: 55 Guiado por angiografia: 54	FFR: 1 Angiografia: 0	NR	NR	HR 0.,45 (0,108-6,612)
Fournier et al.¹⁵	2019	627	Guiado por FFR: 198 Guiado por angiografia: 429	FFR: 21 Angiografia: 79	FFR: 11 Angiografia: 34	FFR: 17 Angiografia: 27	FFR: 42 Angiografia: 113
Toth et al.¹⁹	2019	172	Guiado por FFR: 88 Guiado por angiografia: 84	FFR: 3 Angiografia: 2	FFR: 0 Angiografia: 2	FFR: 2 Angiografia: 4	FFR: 5 Angiografia: 6

Open in a new tab

IM: infarto do miocárdio; TVR: revascularização do vaso alvo

Síntese quantitativa dos desfechos

Morte por todas as causas.

A morte por todas as causas foi reportada nos cinco estudos, o que foi considerado para a análise agrupada, para um total de 1.114 pacientes. A estratégia da fisiologia apresentou 0,63 vezes o risco de morte por todas as causas em comparação à estratégia da angiografia (RR = 0,63; IC95% = 0,42–0,96). A Figura 2 descreve a metanálise ponderada para a morte por todas as causas. A análise agrupada demonstrou heterogeneidade insignificante entre os estudos (I2 = 0%; p = 0,55). Em uma análise de sensibilidade, ao recalcular os resultados agrupados da análise primária ao excluir cada estudo por vez, no estudo de Fournier et al. esta diferença de risco desaparece. Este efeito também desapareceu quando limitamos a análise a estudos randomizados controlados (RR = 1,09; IC95% = 0,28–4,3). A Figura 3 descreve a metanálise ponderada para a morte por todas as causas quando só os estudos randomizados controlados foram incluídos.

Infarto do miocárdio.

Para analisar a ocorrência de IM, quatro estudos que incluíam um total de 1.093 pacientes foram agrupados. Não houve diferença significativa entre as duas estratégias (RR = 0,72; IC95% = 0,39–1,33), nem heterogeneidade significativa entre os estudos (I2 = 0%; p = 0,65). A exclusão de qualquer estudo único e dos não-randomizados não alterou o resultado combinado final.

Revascularização do vaso alvo.

Para avaliar a TVR, quatro estudos incluindo um total de 1.093 pacientes foram agrupados. Não houve diferença significativa entre as duas estratégias (RR = 1,25; IC95% = 0,73–2,13), nem heterogeneidade significativa entre os estudos (I2 = 0%; p = 0,55). A exclusão de qualquer estudo único e dos não-randomizados não alterou o resultado combinado final.

MACE.

Para avaliar os MACE, cinco estudos incluindo 1.114 pacientes foram agrupados. Não houve diferença significativa entre as duas estratégias (RR = 0,81; IC95% = 0,62–1,07), nem heterogeneidade significativa entre os estudos (I2 = 0%; p = 1). A exclusão de qualquer estudo único e dos não-randomizados não alterou o resultado combinado final.

Viés do estudo

A inspeção visual do gráfico de funil para os desfechos não revelou nenhuma assimetria entre os estudos (Figura 4). Além disso, o teste de correlação de Begg não foi estatisticamente significante.

Discussão

A sobrevivência tem uma correlação significativamente negativa com a carga obstrutiva da DAC angiográfica. O escore SYNTAX estratifica a complexidade angiográfica da doença arterial coronariana e estabelece o prognóstico de pacientes com MVD, sendo uma ferramenta importante para decidir sobre a melhor estratégia de revascularização.^22,23

Há discordâncias entre a gravidade da significância da angiografia e da fisiologia da DAC, então, o escore SYNTAX, que é obtido ao considerar somente as lesões provocadas por isquemia, pode superar esta limitação. Em comparação com o clássico escore SYNTAX, o escore SYNTAX funcional tem melhor reprodutibilidade e valor prognóstico, reclassificando até 32% dos candidatos ao CABG e gerando implicações em termos de direcionamento terapêutico.^22-24

Se os impactos favoráveis da fisiologia coronariana nos desfechos da ICP podem ou não ser traduzidos em prática cirúrgica tornou-se o tema de nossa investigação.

Nossa metanálise mostrou uma redução de 37% das mortes por todas as causas no grupo guiado pela fisiologia, com redução não estatisticamente significativa em IM e MACE; esses desfechos não estiveram associados ao aumento do TVR. Esses resultados devem ser interpretados considerando os limites intrínsecos a cada um dos estudos, incluindo viés de seleção, já que esta redução desaparece quando somente os estudos randomizados controlados são agrupados para análise.

Ao avaliar os desfechos clínicos na revascularização, há importantes considerações a serem feitas. A primeira é relacionada aos desfechos (peri) procedimento. O tipo de IM deve estar claramente estabelecido ao comparar as estratégias, já que hoje é universalmente aceito que o prognóstico do IM espontâneo não é similar ao IM periprocedimento ou o IM tipo 2.^25,26

A história natural da doença é outro ponto importante a ser considerado como novo paradigma, com o foco na doença em si (aterosclerose) e não no sintoma (isquemia).^25,27 A composição da placa, avaliada por algumas características da imagem, aparentemente é o principal determinante do prognóstico, até mais do que o nível da estenose coronária ou sua localização.^28-30 Isso pode explicar o melhor prognóstico associado à completa revascularização no contexto da síndrome coronária aguda, na qual as placas em lesões não culpadas aparentemente possuem características instáveis, contrastando com os achados na doença coronariana estável.³¹

A terceira consideração importante é o tipo de revascularização. Os benefícios bem definidos do CABG em comparação à ICP guiada pela angiografia, como reportado nos estudos ASCERT, SYNTAX, FREEDOM e BEST, usam critérios anatômicos e não-funcionais para guiar a revascularização e vêm antes da tecnologia de stent farmacológico da nova geração.^8-12

Uma diferença considerável entre o CABG e a ICP depende dos efeitos protetivos da progressão da doença aterosclerótica. Sabe-se que a maioria das estenoses relacionadas ao IM está localizada no terço proximal da árvore coronária. Também sabe-se que a maioria dos IMs advém de placas não-significantes. Enxertos cirúrgicos de bypass normalmente são implantados distalmente na circulação coronária, promovendo “um efeito de colateralização” na revascularização, e parece concebível que o benefício prognóstico do CABG possa ser explicado pela proteção contra eventos coronários, independentemente da gravidade da estenose do vaso enxertado. O conceito de revascularização baseado na fisiologia, e não no tipo de placa, elimina o efeito protetor do bypass cirúrgico.^28-30,32

O conceito da completa revascularização surgiu de estudos prévios sobre o CABG, enquanto algumas publicações demonstravam que pacientes que estavam completamente revascularizados tinham um benefício em termos de mortalidade em relação àqueles que estavam revascularizados de forma incompleta, o que estabeleceu um padrão para o campo do CABG.^33-35

A revascularização baseada na fisiologia também traz o conceito da revascularização completamente anatômica versus funcional. Se, por um lado, o uso da fisiologia coronária reduz o número de vasos enxertados, ou até de cirurgias, sem a circulação extracorpórea, por outro aumenta a taxa de revascularização incompleta anatomicamente definida.¹⁹

O uso da revascularização guiada pela fisiologia demonstrou reduzir a taxa de MACE nos pacientes com MVD, com ponto de corte de FFR de 0,78, mostrando associação significativa entre a medida de FFR pré-operatório do vaso alvo e a funcionalidade da anastomose após seis meses. Essas conclusões também são apoiadas por Botman et al.,³⁶ para quem as lesões com FFR > 0,75 estão associadas ao aumento significativo do risco de oclusão do enxerto (p <0,0001).^18,19,36,37

Considerando as diferenças descritas na suscetibilidade à competitividade de fluxo, parece provável que o tipo de conduta usada nos estudos FARGO e GRAFFITI (nos quais uma grande proporção dos enxertos eram enxerto de veia safena – EVS) versus o estudo IMPAG (no qual somente enxertos arteriais eram utilizados) possa explicar os resultados contraditórios.^14,19,38

O estudo FAME 3 vai comparar, de forma multicêntrica e randomizada, a ICP guiada por FFR com stents farmacológicos contemporâneos com o CABG em pacientes com a doença de 3 vasos. Porém, não vai responder sobre a comparação entre o CABG guiado por fisiologia e o CABG guiado pela angiografia.³⁹

Finalmente, o papel do acompanhamento neste contexto também deve ser considerado. Quanto mais grave a estenose coronária, maior o risco de IM, mas são as placas não-significativas as responsáveis pela maioria dos IMs. Também sabemos que a principal causa de morte nesses pacientes com DAC é relacionada ao coração, e que o IM é uma causa de morte cardíaca; então, as terapias para reduzir o IM ou a morte cardiovascular vão, consequentemente, reduzir a mortalidade.³²

Podemos considerar o estudo STICH como exemplo, comparando o tratamento com terapia clínica somado ao CABG e somente a terapia clínica em pacientes com DAC e insuficiência cardíaca, com fração de ejeção reduzida. Após cinco anos de acompanhamento, a análise da intenção de tratamento não demonstrou diferenças significativas entre as duas estratégias com relação ao desfecho primário de morte por todas as causas. Porém, após o período de acompanhamento ter sido estendido para dez anos, uma redução significativa na mortalidade foi encontrada para o CABG somado à terapia clínica, em comparação à terapia clínica somente (HR, 0,84; IC95%: 0,73-0,97; p=0,02). Outro exemplo é o estudo FAME 2, no qual os dados publicados após cinco anos mostram uma forte tendência a baixas taxas de infarto do miocárdio no grupo ICP (HR 0,66; IC95% 0,43-1,00; p = 0,049), uma diferença que só foi significativa para o IM espontâneo (HR 0,62; IC95%; p = 0,04), e não para o IM periprocedimento. Recentemente, o estudo ISCHEMIA mostrou que, em um acompanhamento prévio, o desfecho composto primário (morte cardiovascular, IM ou hospitalização devido à angina instável ou insuficiência cardíaca) foi mais frequente no grupo com a estratégia invasiva do que no grupo da estratégia conservadora (5,3% vs. 3,4% após seis meses), devido aos IMs relacionados ao procedimento. Porém, em um acompanhamento posterior, depois de aproximadamente dois anos, as curvas dos eventos se cruzaram e, após cinco anos, a incidência do desfecho primário foi um pouco maior no grupo da estratégia conservadora (18,2% e 16,4%). Então, parece que para se ter um impacto nos desfechos duros, como morte por todas as causas, temos que estender a duração do período de observação.^25,40,41

Em nosso estudo, a redução da morte por todas as causas em um contexto de redução não significativa do IM e MACE deve ser interpretada com cautela, já que esta situação pode estar relacionada a mortes causadas por motivos relacionados ao coração. Seria interessante não só avaliar se essas mortes têm relação com o coração, mas também estender o acompanhamento dos estudos para observar se as curvas dos desfechos duros divergem em períodos mais longos, possibilitando chegar a conclusões definitivas. É importante observar que somente o estudo de Fournier et al.,¹⁸ tem um período de acompanhamento mais longo do que cinco anos, o que pode explicar os resultados, já que a redução no desfecho composto morte por todas as causas e IM, apoiando a estratégia da fisiologia, só foi encontrada quando o período de acompanhamento foi estendido.¹⁵

Limitações

As conclusões tiradas desta metanálise estão sujeitas às limitações e diferenças dos estudos originais incluídos na análise. A limitação desta metanálise é a presença de estudos com amostras menores e abrangentes, e resultados de sobrevivência de longo prazo. Outra limitação é representada por um viés de seleção intrínseco. Diversas decisões sobre revascularização na estratégia guiada pela fisiologia foram desviadas da indicação funcional nos estudos incluídos, e os autores justificaram que isso esteve relacionado a causas técnicas e, em alguns casos, à relutância para adiar a revascularização. Como mencionado, como a causa de morte não era conhecida, isso inclui mortes não relacionadas ao coração, ou seja, não ligadas à escolha da estratégia da revascularização. Outra limitação foi que com a inclusão de dois estudos retrospectivos e observacionais, alguns pacientes incluídos neste registro podem ter sido tratados com ICP guiada pela fisiologia, e não pelo CABG.

Conclusão

Esta metanálise demonstra uma redução na morte por todas as causas quando a estratégia do CABG guiado pela fisiologia foi utilizada. Porém, o curto período de acompanhamento, a amostra pequena dos estudos incluídos e a não-discriminação de causas de morte podem justificar essas conclusões. Estudos com períodos mais longos de observação são necessários para se chegar a conclusões mais robustas e definitivas.

Footnotes

Fontes de financiamento

O presente estudo não teve fontes de financiamento externas.

Vinculação acadêmica

Não há vinculação deste estudo a programas de pós-graduação.

Aprovação ética e consentimento informado

Este artigo não contém estudos com humanos ou animais realizados por nenhum dos autores.

Referências

1.Knuuti J, Wijns W, Saraste A, Capodanno D, Barbato E, Funck-Brentano C, et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes: The Task Force for the diagnosis and management of chronic coronary syndromes of the European Society of Cardiology (ESC) Eur Heart J. 2020;41(3):407–477. doi: 10.1093/eurheartj/ehz425. [DOI] [PubMed] [Google Scholar]; Knuuti J, Wijns W, Saraste A, Capodanno D, Barbato E, Funck-Brentano C, et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes: The Task Force for the diagnosis and management of chronic coronary syndromes of the European Society of Cardiology (ESC). Eur Heart J. 2020;41(3):407-77. [DOI] [PubMed]
2.Masdjedi K, Daemen J. Angiography-Based FFR: Reevaluating the Role of the Pressure Wire. Card Interv Today. 2019;13(3):28–33. [Google Scholar]; Masdjedi K, Daemen J. Angiography-Based FFR: Reevaluating the Role of the Pressure Wire. Card Interv Today. 2019;13(3):28-33.
3.Morris PD, Curzen N, Gunn JP. Angiography-derived fractional flow reserve: more or less physiology? J Am Heart Assoc. 2020;9(6):e015586. doi: 10.1161/JAHA.119.015586. [DOI] [PMC free article] [PubMed] [Google Scholar]; Morris PD, Curzen N, Gunn JP. Angiography-derived fractional flow reserve: more or less physiology?.J Am Heart Assoc. 2020;9(6):e015586. [DOI] [PMC free article] [PubMed]
4.Neumann FJ, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Benedetto U, et al. 2018 ESC/EACTS guidelines on myocardial revascularization. Eur Heart J. 2019;40(2):87–165. [Google Scholar]; Neumann FJ, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Benedetto U, et al. 2018 ESC/EACTS guidelines on myocardial revascularization. Eur Heart J. 2019;40(2):87-165.
5.De Bruyne B, Pijls NH, Kalesan B, Barbato E, Tonino PAL, Piroth Z, et al. Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease. N Engl J Med. 2012;367:991–1001. doi: 10.1056/NEJMoa1205361. [DOI] [PubMed] [Google Scholar]; De Bruyne B, Pijls NH, Kalesan B, Barbato E, Tonino PAL, Piroth Z, et al. Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease. N Engl J Med. 2012;367:991-1001. [DOI] [PubMed]
6.Pijls NH, Schaardenburgh P, Manoharan G, Boersma E, Bech JW, van’t Veer M, et al. Percutaneous coronary intervention of functionally nonsignificant stenosis: 5-year follow-up of the DEFER study. J Am Coll Cardiol. 2007;49(21):2105–2111. doi: 10.1016/j.jacc.2007.01.087. [DOI] [PubMed] [Google Scholar]; Pijls NH, Schaardenburgh P, Manoharan G, Boersma E, Bech JW, van’t Veer M, et al. Percutaneous coronary intervention of functionally nonsignificant stenosis: 5-year follow-up of the DEFER study. J Am Coll Cardiol. 2007;49(21):2105-11. [DOI] [PubMed]
7.Tonino PA, De Bruyne B, Pijls NH, Siebert U, Ikeno F, van’t Veer M, et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med. 2009;360(3):213–224. doi: 10.1056/NEJMoa0807611. [DOI] [PubMed] [Google Scholar]; Tonino PA, De Bruyne B, Pijls NH, Siebert U, Ikeno F, van’t Veer M, et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med. 2009;360(3):213-24. [DOI] [PubMed]
8.Weintraub WS, Grau-Sepulveda MV, Weiss JM, O’Brien SM, Peterson ED, Kolm P, et al. Comparative effectiveness of revascularization strategies. N Engl J Med. 2012;366(16):1467–1476. doi: 10.1056/NEJMoa1110717. [DOI] [PMC free article] [PubMed] [Google Scholar]; Weintraub WS, Grau-Sepulveda MV, Weiss JM, O’Brien SM, Peterson ED, Kolm P, et al. Comparative effectiveness of revascularization strategies. N Engl J Med. 2012;366(16):1467-76. [DOI] [PMC free article] [PubMed]
9.Serruys PW, Morice MC, Kappetein AP, Colombo A, Holmes DR, Mack MJ, et al. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med. 2009;360(10):961–972. doi: 10.1056/NEJMoa0804626. [DOI] [PubMed] [Google Scholar]; Serruys PW, Morice MC, Kappetein AP, Colombo A, Holmes DR, Mack MJ, et al. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med. 2009;360(10):961-72. [DOI] [PubMed]
10.Mohr FW, Morice MC, Kappetein AP, Feldman TE, Ståhle E, Colombo A, et al. Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year follow-up of the randomised, clinical SYNTAX trial. Lancet. 2013;381(9867):629–638. doi: 10.1016/S0140-6736(13)60141-5. [DOI] [PubMed] [Google Scholar]; Mohr FW, Morice MC, Kappetein AP, Feldman TE, Ståhle E, Colombo A, et al. Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year follow-up of the randomised, clinical SYNTAX trial. Lancet. 2013;381(9867):629-38. [DOI] [PubMed]
11.Farkouh ME, Domanski M, Sleeper LA, Siami FS, Dangas G, Mack M, et al. Strategies for multivessel revascularization in patients with diabetes. N Engl J Med. 2012;367(25):2375–2384. doi: 10.1056/NEJMoa1211585. [DOI] [PubMed] [Google Scholar]; Farkouh ME, Domanski M, Sleeper LA, Siami FS, Dangas G, Mack M, et al. Strategies for multivessel revascularization in patients with diabetes. N Engl J Med. 2012;367(25):2375-84. [DOI] [PubMed]
12.Park SJ, Ahn JM, Kim YH, Park DW, Yun SC, Lee JY, et al. Trial of everolimus-eluting stents or bypass surgery for coronary disease. N Engl J Med. 2015;372(13):1204–1212. doi: 10.1056/NEJMoa1415447. [DOI] [PubMed] [Google Scholar]; Park SJ, Ahn JM, Kim YH, Park DW, Yun SC, Lee JY, et al. Trial of everolimus-eluting stents or bypass surgery for coronary disease. N Engl J Med. 2015;372(13):1204-12. [DOI] [PubMed]
13.Toth G, De Bruyne B, Casselman F, De Vroey F, Pyxaras S, Serafino L, et al. Fractional flow reserve-guided versus angiography- guided coronary artery bypass graft surgery. Circulation. 2013;128(13):1405–1411. doi: 10.1161/CIRCULATIONAHA.113.002740. [DOI] [PubMed] [Google Scholar]; Toth G, De Bruyne B, Casselman F, De Vroey F, Pyxaras S, Serafino L, et al. Fractional flow reserve-guided versus angiography- guided coronary artery bypass graft surgery. Circulation. 2013;128(13):1405-11. [DOI] [PubMed]
14.Thuesen AL, Riber LP, Veien KT, Christiansen EH, Jensen SE, Modrau I, et al. Fractional flow reserve versus angiographically-guided coronary artery bypass grafting. J Am Coll Cardiol. 2018;72(22):2732–2743. doi: 10.1016/j.jacc.2018.09.043. [DOI] [PubMed] [Google Scholar]; Thuesen AL, Riber LP, Veien KT, Christiansen EH, Jensen SE, Modrau I, et al. Fractional flow reserve versus angiographically-guided coronary artery bypass grafting. J Am Coll Cardiol. 2018;72(22):2732-43. [DOI] [PubMed]
15.Fournier S, Toth GG, De Bruyne B, Johnson NP, Ciccarelli G, Xaplanteris P, et al. Six-year follow-up of fractional flow reserve-guided versus angiography-guided coronary artery bypass graft surgery. Circ Cardiovasc Interv. 2018;11(6):e006368. doi: 10.1161/CIRCINTERVENTIONS.117.006368. [DOI] [PubMed] [Google Scholar]; Fournier S, Toth GG, De Bruyne B, Johnson NP, Ciccarelli G, Xaplanteris P, et al. Six-year follow-up of fractional flow reserve-guided versus angiography-guided coronary artery bypass graft surgery. Circ Cardiovasc Interv. 2018;11(6):e006368. [DOI] [PubMed]
16.Moscona JC, Stencel JD, Milligan G, Salmon C, Maini R, Katigbak P, et al. Physiologic assessment of moderate coronary lesions: a step towards complete revascularization in coronary artery bypass grafting. Ann Transl Med. 2018;6(15):300–300. doi: 10.21037/atm.2018.06.31. [DOI] [PMC free article] [PubMed] [Google Scholar]; Moscona JC, Stencel JD, Milligan G, Salmon C, Maini R, Katigbak P, et al. Physiologic assessment of moderate coronary lesions: a step towards complete revascularization in coronary artery bypass grafting. Ann Transl Med. 2018;6(15):300. [DOI] [PMC free article] [PubMed]
17.Rioufol G. FUTURE trial: Treatment strategy in multivessel coronary disease patients based on fractional flow reserve. Presented at: European Society of Cardiology (ESC) 2018. 2018 Aug 25; Munich, Germany. [Google Scholar]; Rioufol G. FUTURE trial: Treatment strategy in multivessel coronary disease patients based on fractional flow reserve. Presented at: European Society of Cardiology (ESC) 2018. August 25, 2018. Munich, Germany.
18.Fournier S, Toth GG, Colaiori I, De Bruyne B, Barbato E. Long-term patency of coronary artery bypass grafts after fractional flow reserve-guided implantation. Circ Cardiovasc Interv. 2019;12(5):e007712. doi: 10.1161/CIRCINTERVENTIONS.118.007712. [DOI] [PubMed] [Google Scholar]; Fournier S, Toth GG, Colaiori I, De Bruyne B, Barbato E. Long-term patency of coronary artery bypass grafts after fractional flow reserve-guided implantation. Circ Cardiovasc Interv. 2019;12(5):e007712. [DOI] [PubMed]
19.Toth GG, De Bruyne B, Kala P, Ribichini FL, Casselman F, Ramos R, et al. Graft patency after FFR-guided versus angiography- guided coronary artery bypass grafting. The GRAFFITI trial. EuroIntervention. 2019;15(11):e999–e1005. doi: 10.4244/EIJ-D-19-00463. [DOI] [PubMed] [Google Scholar]; Toth GG, De Bruyne B, Kala P, Ribichini FL, Casselman F, Ramos R, et al. Graft patency after FFR-guided versus angiography- guided coronary artery bypass grafting. The GRAFFITI trial. EuroIntervention. 2019;15(11):e999-1005. [DOI] [PubMed]
20.Spadaccio C, Glineur D, Barbato E, Di Franco A, Oldroyd KG, Biondi-Zoccai G, et al. Fractional Flow Reserve-Based Coronary Artery Bypass Surgery: Current Evidence and Future Directions. JACC Cardiovasc Interv. 2020;13(9):1086–1096. doi: 10.1016/j.jcin.2019.12.017. [DOI] [PMC free article] [PubMed] [Google Scholar]; Spadaccio C, Glineur D, Barbato E, Di Franco A, Oldroyd KG, Biondi-Zoccai G, et al. Fractional Flow Reserve-Based Coronary Artery Bypass Surgery: Current Evidence and Future Directions. JACC Cardiovasc Interv. 2020;13(9):1086-96. [DOI] [PMC free article] [PubMed]
21.DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177–188. doi: 10.1016/0197-2456(86)90046-2. [DOI] [PubMed] [Google Scholar]; DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177-88. [DOI] [PubMed]
22.Serruys PW, Morice MC, Kappetein AP, Colombo A, Holmes DR, Mack MJ, et al. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med. 2009;360(10):961–972. doi: 10.1056/NEJMoa0804626. [DOI] [PubMed] [Google Scholar]; Serruys PW, Morice MC, Kappetein AP, Colombo A, Holmes DR, Mack MJ, et al. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med. 2009;360(10):961-72. [DOI] [PubMed]
23.Thuijs DJFM, Kappetein AP, Serruys PW, Mohr FW, Morice MC, Mack MJ, et al. Percutaneous coronary intervention versus coronary artery bypass grafting in patients with three-vessel or left main coronary artery disease: 10-year follow-up of the multicentre randomised controlled SYNTAX trial. Lancet. 2019;394(10206):1325–1334. doi: 10.1016/S0140-6736(19)31997-X. [DOI] [PubMed] [Google Scholar]; Thuijs DJFM, Kappetein AP, Serruys PW, Mohr FW, Morice MC, Mack MJ, et al. Percutaneous coronary intervention versus coronary artery bypass grafting in patients with three-vessel or left main coronary artery disease: 10-year follow-up of the multicentre randomised controlled SYNTAX trial. Lancet. 2019;394(10206):1325-34. [DOI] [PubMed]
24.Serruys PW, Kogame N, Katagiri Y, Modolo R, Buszman PE, Íñiguez-Romo A, et al. Clinical outcomes of state-of-the-art percutaneous coronary revascularisation in patients with three-vessel disease: two-year follow-up of the SYNTAX II study. EuroIntervention. 2019;15(3):e244–e252. doi: 10.4244/EIJ-D-18-00980. [DOI] [PubMed] [Google Scholar]; Serruys PW, Kogame N, Katagiri Y, Modolo R, Buszman PE, Íñiguez-Romo A, et al. Clinical outcomes of state-of-the-art percutaneous coronary revascularisation in patients with three-vessel disease: two-year follow-up of the SYNTAX II study. EuroIntervention. 2019;15(3):e244-52. [DOI] [PubMed]
25.Maron DJ, Hochman JS, Reynolds HR, Bangalore S, O’Brien SM, Boden WE, et al. Initial Invasive or Conservative Strategy for Stable Coronary Disease. N Engl J Med. 2020;382:1395–1407. doi: 10.1056/NEJMoa1915922. [DOI] [PMC free article] [PubMed] [Google Scholar]; Maron DJ, Hochman JS, Reynolds HR, Bangalore S, O’Brien SM, Boden WE, et al. Initial Invasive or Conservative Strategy for Stable Coronary Disease. N Engl J Med. 2020;382:1395-407. [DOI] [PMC free article] [PubMed]
26.Ben-Yehuda O, Chen S, Redfors B, McAndrew T, Crowley A, Kosmidou J, et al. I Impact of large periprocedural myocardial infarction on mortality after percutaneous coronary intervention and coronary artery bypass grafting for left main disease: an analysis from the EXCEL trial. Eur Heart J. 2019;40(24):1930–1941. doi: 10.1093/eurheartj/ehz113. [DOI] [PubMed] [Google Scholar]; Ben-Yehuda O, Chen S, Redfors B, McAndrew T, Crowley A, Kosmidou J, et al. I Impact of large periprocedural myocardial infarction on mortality after percutaneous coronary intervention and coronary artery bypass grafting for left main disease: an analysis from the EXCEL trial. Eur Heart J. 2019;40(24):1930-41. [DOI] [PubMed]
27.Lardinois CK. Atherosclerosis - Know your risk -is time for a paradigm shift? US Endocrinol. 2014;10(2):105–110. [Google Scholar]; Lardinois CK. Atherosclerosis - Know your risk -is time for a paradigm shift? US Endocrinol. 2014;10(2):105-10.
28.Jeon C, Candia SC, Wang JC, Holper EM, Ammerer M, Kuntz RE, et al. Relative spatial distributions of coronary artery bypass graft insertion and acute thrombosis: a model for protection from acute myocardial infarction. Am Heart J. 2010;160(1):195–201. doi: 10.1016/j.ahj.2010.04.004. [DOI] [PubMed] [Google Scholar]; Jeon C, Candia SC, Wang JC, Holper EM, Ammerer M, Kuntz RE, et al. Relative spatial distributions of coronary artery bypass graft insertion and acute thrombosis: a model for protection from acute myocardial infarction. Am Heart J. 2010;160(1):195-201. [DOI] [PubMed]
29.Wang JC, Normand SL, Mauri L, Kuntz RE. Coronary artery spatial distribution of acute myocardial infarction occlusions. Circulation. 2004;110(3):278–284. doi: 10.1161/01.CIR.0000135468.67850.F4. [DOI] [PubMed] [Google Scholar]; Wang JC, Normand SL, Mauri L, Kuntz RE. Coronary artery spatial distribution of acute myocardial infarction occlusions. Circulation. 2004;110(3):278-84. [DOI] [PubMed]
30.Mushtaq S, Goncalves P, Garcia-Garcia HM, Pontone G, Bartorelli A, Bertella E, et al. Long-term prognostic effect of coronary atherosclerotic burden: validation of the computed tomography-Leaman score. Circ Cardiovasc Imaging. 2015;8(2):e002332. doi: 10.1161/CIRCIMAGING.114.002332. [DOI] [PubMed] [Google Scholar]; Mushtaq S, Goncalves P, Garcia-Garcia HM, Pontone G, Bartorelli A, Bertella E, et al. Long-term prognostic effect of coronary atherosclerotic burden: validation of the computed tomography-Leaman score. Circ Cardiovasc Imaging. 2015;8(2):e002332. [DOI] [PubMed]
31.Al-Abdouh A, Barbarawi M, Bizanti A, Abudaya I, Upadhrasta S, Elias H, et al. Complete revascularization in patients with STEMI and multi-vessel disease: A meta-analysis of randomized controlled trials. Cardiovasc Revasc Med. 2020;21(5):684–691. doi: 10.1016/j.carrev.2020.01.020. [DOI] [PubMed] [Google Scholar]; Al-Abdouh A, Barbarawi M, Bizanti A, Abudaya I, Upadhrasta S, Elias H, et al. Complete revascularization in patients with STEMI and multi-vessel disease: A meta-analysis of randomized controlled trials. Cardiovasc Revasc Med. 2020;21(5):684-91. [DOI] [PubMed]
32.Doenst T, Haverich A, Serruys P, Bonow RO, Kappetein P, Falk V, et al. PCI and CABG for treating stable coronary artery disease: JACC Review Topic of the Week. J Am Coll Cardiol. 2019;73(8):964–976. doi: 10.1016/j.jacc.2018.11.053. [DOI] [PubMed] [Google Scholar]; Doenst T, Haverich A, Serruys P, Bonow RO, Kappetein P, Falk V, et al. PCI and CABG for treating stable coronary artery disease: JACC Review Topic of the Week. J Am Coll Cardiol. 2019;73(8):964-76. [DOI] [PubMed]
33.Buda AJ, Macdonald IL, Anderson MJ, Strauss HD, David TE, Berman ND. Long-term results following coronary bypass operation. Importance of preoperative actors and complete revascularization. J Thorac Cardiovasc Surg. 1981;82(3):383–390. [PubMed] [Google Scholar]; Buda AJ, Macdonald IL, Anderson MJ, Strauss HD, David TE, Berman ND. Long-term results following coronary bypass operation. Importance of preoperative actors and complete revascularization. J Thorac Cardiovasc Surg. 1981;82(3):383-90. [PubMed]
34.Bell MR, Gersh BJ, Schaff HV, Holmes DR, Jr, Fisher LD, Alderman EL, et al. Effect of completeness of revascularization on long-term outcome of patients with three-vessel disease undergoing coronary artery bypass surgery. A report from the Coronary Artery Surgery Study (CASS) Registry. Circulation. 1992;86(2):446–457. doi: 10.1161/01.cir.86.2.446. [DOI] [PubMed] [Google Scholar]; Bell MR, Gersh BJ, Schaff HV, Holmes Jr DR, Fisher LD, Alderman EL, et al. Effect of completeness of revascularization on long-term outcome of patients with three-vessel disease undergoing coronary artery bypass surgery. A report from the Coronary Artery Surgery Study (CASS) Registry. Circulation. 1992;86(2):446-57. [DOI] [PubMed]
35.Ong AT, Serruys PW. Complete revascularization: coronary artery bypass graft surgery versus percutaneous coronary intervention. Circulation. 2006;114(3):249–255. doi: 10.1161/CIRCULATIONAHA.106.614420. [DOI] [PubMed] [Google Scholar]; Ong AT, Serruys PW. Complete revascularization: coronary artery bypass graft surgery versus percutaneous coronary intervention. Circulation. 2006;114(3):249-55. [DOI] [PubMed]
36.Botman K, Pijls NH, Bech JW, Aarnoudse W, Peels K, Straten BV, et al. Percutaneous coronary intervention or bypass surgery in multivessel disease? A tailored approach based on coronary pressure measurement. Catheter Cardiovasc Interv. 2004;63(2):184–191. doi: 10.1002/ccd.20175. [DOI] [PubMed] [Google Scholar]; Botman K, Pijls NH, Bech JW, Aarnoudse W, Peels K, Straten BV, et al. Percutaneous coronary intervention or bypass surgery in multivessel disease? A tailored approach based on coronary pressure measurement. Catheter Cardiovasc Interv. 2004;63(2):184-91. [DOI] [PubMed]
37.Kern MJ, Seto AH. High FFR strongly predicts arterial graft dysfunction: pure benefit in a pure population? Eur Heart J. 2019;40(29):2429–2431. doi: 10.1093/eurheartj/ehz371. [DOI] [PubMed] [Google Scholar]; Kern MJ, Seto AH. High FFR strongly predicts arterial graft dysfunction: pure benefit in a pure population? Eur Heart J. 2019;40(29):2429-31. [DOI] [PubMed]
38.Glineur D, Grau JB, Etienne PY, Benedetto U, Fortier JH, Papadatos S, et al. Impact of preoperative fractional flow reserve on arterial bypass graft anastomotic function: the IMPAG trial. Eur Heart J. 2019;40(29):2421–2428. doi: 10.1093/eurheartj/ehz329. [DOI] [PubMed] [Google Scholar]; Glineur D, Grau JB, Etienne PY, Benedetto U, Fortier JH, Papadatos S, et al. Impact of preoperative fractional flow reserve on arterial bypass graft anastomotic function: the IMPAG trial. Eur Heart J. 2019;40(29):2421-28. [DOI] [PubMed]
39.Zimmermann FM, De Bruyne B, Pijls NH, Desai M, Oldroyd KG, Park SJ, et al. Rationale and design of the Fractional Flow Reserve versus Angiography for Multivessel Evaluation (FAME) 3 Trial: a comparison of fractional flow reserve-guided percut aneous coronary intervention and coronary artery bypass graft surgery in patients with multivessel coronary artery disease. Am Heart J. 2015;170(4):619.e2–626.e2. doi: 10.1016/j.ahj.2015.06.024. [DOI] [PubMed] [Google Scholar]; Zimmermann FM, De Bruyne B, Pijls NH, Desai M, Oldroyd KG, Park SJ, et al. Rationale and design of the Fractional Flow Reserve versus Angiography for Multivessel Evaluation (FAME) 3 Trial: a comparison of fractional flow reserve-guided percut aneous coronary intervention and coronary artery bypass graft surgery in patients with multivessel coronary artery disease. Am Heart J. 2015;170(4):619-26.e2. [DOI] [PubMed]
40.Petrie MC, Jhund PS, She L, Adlbrecht C, Doenst T, Panza JA, et al. Ten-Year Outcomes After Coronary Artery Bypass Grafting According to Age in Patients With Heart Failure and Left Ventricular Systolic Dysfunction: An Analysis of the Extended Follow-Up of the STICH Trial (Surgical Treatment for Ischemic Heart Failure) Circulation. 2016;134(18):1314–1324. doi: 10.1161/CIRCULATIONAHA.116.024800. [DOI] [PMC free article] [PubMed] [Google Scholar]; Petrie MC, Jhund PS, She L, Adlbrecht C, Doenst T, Panza JA, et al. Ten-Year Outcomes After Coronary Artery Bypass Grafting According to Age in Patients With Heart Failure and Left Ventricular Systolic Dysfunction: An Analysis of the Extended Follow-Up of the STICH Trial (Surgical Treatment for Ischemic Heart Failure). Circulation. 2016;134(18):1314-24. [DOI] [PMC free article] [PubMed]
41.Xaplanteris P, Fournier S, Pijls NHJ, Fearon WF, Barbato E, Tonino PAL, et al. Five- year outcomes with PCI guided by fractional flow reserve. N Engl J Med. 2018;379(3):250–259. doi: 10.1056/NEJMoa1803538. [DOI] [PubMed] [Google Scholar]; Xaplanteris P, Fournier S, Pijls NHJ, Fearon WF, Barbato E, Tonino PAL, et al. Five- year outcomes with PCI guided by fractional flow reserve. N Engl J Med. 2018;379(3):250-9. [DOI] [PubMed]

Arq Bras Cardiol. 2021 Nov 22;117(6):1115–1123. [Article in English]

Physiology or Angiography-Guided Coronary Artery Bypass Grafting: A Meta-Analysis

José Martins ^1,^✉, Vera Afreixo ², Luís Santos ¹, Luís Fernandes ³, Ana Briosa ¹

Abstract

Background:

While invasive coronary angiography is considered the gold standard for the diagnosis of coronary artery disease (CAD) involving the epicardial coronary vessels, coronary physiology-guided revascularization represents a contemporary gold-standard practice for the invasive management of patients with intermediate CAD. Nevertheless, the long-term results of assessing the severity of stenosis through physiology compared to the angiogram as the guide to bypass surgery – coronary artery bypass grafting (CABG) are still uncertain. This meta-analysis aims to assess the clinical outcomes of a physiology guided CABG compared to the angiography-guided CABG.

Objectives:

We sought to determine if outcomes differ between a physiology guided CABG compared to an angiography-guided CABG.

Methods:

We searched Medline, EMBASE, and the Cochrane Library. The last date for this search was June 2020, and all of the previous studies were included. We conducted a pooled risk-ratio meta-analysis for four main outcomes: all-cause death, myocardial infarction (MI), target vessel revascularization (TVR) and major adverse cardiovascular events (MACE). P-value <0.05 was considered as statistically significant. Heterogeneity was assessed with Cochran's Q test and quantified by the I² index.

Results:

We identified five studies that included a total of 1,114 patients. A pooled meta-analysis showed no significant difference between a physiology guided strategy and an angiography-guided strategy in MI (risk ratio [RR] = 0.72; 95%CI, 0.39–1.33; I2 = 0%; p = 0.65), TVR (RR = 1.25; 95%CI = 0.73–2.13; I2 = 0%; p = 0.52), or MACE (RR = 0.81; 95%CI = 0.62–1.07; I2 = 0%; p = 1). The physiology guided strategy has 0.63 times the risk of all-cause death compared to the angiography-guided strategy (RR = 0.63; 95%CI = 0.42–0.96; I2 = 0%; p = 0.55).

Conclusion:

This meta-analysis demonstrated a reduction in all-cause death when a physiology guided CABG strategy was used. Nevertheless, the short follow-up period, small sample size of the included studies and the non-discrimination of the causes of death can largely justify these conclusions. Studies with an extended follow-up period of observation are required to draw more robust and definitive conclusions.

Keywords: Coronary Artery Disease, Angiography, Metanalysis, Coronary Artery/physiology, Coronary Angiography, Coronary Artery Bypass

Introduction

Invasive coronary angiography is considered as the gold standard for the diagnosis of coronary artery disease (CAD) involving the epicardial coronary vessels.¹ Nevertheless, visual assessment by traditional coronary angiography is unable to distinguish if a coronary stenosis is hemodynamically significant, particularly in intermediate CAD, so there are often discordances between the angiographic severity and the physiological significance of CAD.^2,3 Discrepancies occur because, unlike angiography, physiology incorporates the combined and inter-related effects of coronary flow and microvascular resistance.³

There is growing evidence supporting the clinical benefit and cost-effectiveness of coronary physiology guided percutaneous revascularization, either by indices based on hyperemia or indices based on pressure difference during a specific period in diastole, compared to percutaneous revascularization based on coronary angiography.^4-7 However, the long-term results of assessing the severity of stenosis through physiology compared to the angiogram as the guide to bypass surgery are still uncertain.

Cardiac surgeons are, in the light of the results, progressively guiding multivessel disease (MVD) revascularization based on coronary physiology. However, whether this decision entails better long-term clinical outcomes or not is still unclear. Recommendations on the use of CABG compared with medical therapy or percutaneous coronary intervention (PCI) are entirely based on studies that used anatomical and non-functional criteria to guide revascularization.^8-12

Given this data, several authors have already evaluated the potential clinical benefit of physiology guided coronary bypass surgery in addition to anatomic detail for surgical decisions.^13-20 In this article, we extend the work of Spadaccio et al.²⁰ by pooling all results from randomized and non-randomized studies to assess the effect on clinical outcomes between a physiology guided CABG compared to angiography-guided CABG.²⁰

Methods

Data sources and searches

We systematically searched Medline, Embase, and the Cochrane Library for relevant published articles. The last date for this search was June 2020, and all of the previous studies were included in the search. Previous qualitative and systematic reviews, if available, were checked for additional studies. The following query term was used: “Coronary physiology” or “Fractional Flow Reserve” or “FFR” or “Instant Wave-Free Ratio” or “iFR” or “Coronary Artery Bypass Graft” or “CABG”. Further studies were sought by means of a manual search of secondary sources, including references from primary articles. No language restrictions were enforced.

Study selection

Citations were first screened at the title/abstract level by two independent reviewers (JM and LS), and complete manuscripts were retrieved if potentially pertinent. Disagreements were resolved after consensus. The identified articles were independently appraised by the same reviewers according to the following inclusion criteria: articles with clinical outcomes comparing the two strategies for CABG revascularization (physiology vs angiography). Disputes regarding the inclusion criteria were resolved by consensus. Studies comparing the two strategies that did not report clinical outcomes were excluded. Studies that, despite the evaluation of clinical outcomes, did not report the strategy used in detail, were also excluded (Figure 1).

Endpoints

The studied endpoints were: all-cause death, myocardial infarction (MI), target vessel revascularization (TVR) and major adverse cardiovascular events (MACE) during the follow-up period.

MACE was defined as a composite of death, myocardial infarction, or any revascularization by Moscona et al.,¹⁶ Fournier et al.¹⁸ and as composite of death, myocardial infarction, stroke, or any revascularization in the FARGO, FUTURE and GRAFFITI studies during the follow-up period.^13-19

Statistical analysis

To calculate the pooled effect estimates, we used the inverse variance assuming a fixed-effect model and the DerSimonian and Laird method assuming a random-effect model.²¹ Homogeneity among the studies was evaluated using the Cochran's Q test and the I2 statistic (the values of 0.25, 0.50, and 0.75 indicated low, moderate, and high levels of heterogeneity, respectively). P-value <0.05 was considered statistically significant. Publication bias was evaluated using the funnel plot. We performed a sensitivity analysis to show the impact of each study on the results. MetaXL 2.0 (EpiGear International Pty Ltd, Wilston, Queensland, Australia) was used to calculate the pooled risk difference effect size (difference between the risk between revascularization and conservative management groups).

Results

Study identification

Database searches initially retrieved 372 citations. Of these, 6 duplicate studies and 321 articles were excluded after the review of the title or abstract. After a thorough assessment according to the selection criteria, we further excluded 40 studies. A final total of five studies were included in the analysis. These five studies included 1,114 patients: 403 in the physiology guided group and 711 the angiography-guided group.

Characteristics of the included studies

Of the five included studies, three were randomized and two were non-randomized, observational, and retrospective in design (Tables 1 and 2).

Table 1. Characteristics of the included studies.

Author	Year	N total	N Strategy	FU	Study design	Conduits	Graft patency FU	Major clinical conclusions
Moscona et al.¹⁶	2018	109	FFR/iFR-guided: 14 Angiography-guided: 95	18 months	Retrospective	Arterial conduits: 92.9% (FFR- group; 90.5% Angiography-group) SVG: 85.7% (FFR- group;76.8% Angiography-group)	NR	A trend toward reduction in MACE (7.1% vs. 11.6%, P=0.369) and angina (0.0% vs. 6.3%, P=0.429) in the FFR/iFR group compared to the angiography group
Thuesen et al.¹⁴	2018	97	FFR-guided: 49 Angiography-guided: 48	Six months	RCT	Arterial conduits: 37%	Graft failures of all grafts were similar in both groups (16% vs. 12%; p = 0.97).	Rates of death, MI, and stroke were similar in the study groups. All-cause mortality at six months was 0% in the FFR-guided group and 4.1% in the angiography-guided group; one patient died because of pulmonary embolism, and one died because of mediastinitis
Rioufol et al.¹⁷	2018	109	FFR-guided: 55 Angiography-guided: 54	One year	RCT	NR	NR	FFR in all-comer multivessel-disease patients did not demonstrate any improvement in the primary composite endpoint composite of all-cause mortality, MI, repeat revascularization, or stroke through one year (14.6% vs 14.4%; HR 0.97; 95%CI 0.69-1.36) Risk of death was significantly higher in the FFR-guided arm (3.7% vs 1.5%; P = 0.036)
Fournier et al.¹⁵	2019	627	FFR-guided: 198 Angiography-guided: 429	Six years	Retrospective	Arterial conduits: 64% SVG: 36%	The occlusion rate was significantly lower with FFR-guided as compared with angiography-guided grafts	FFR-guided CABG is associated with a significant reduction in the rate of overall death or myocardial infarction (HR 0.59 [95% CI, 0.38–0.93]; P=0.020)
Toth et al.¹⁹	2019	172	FFR-guided: 88 Angiography-guided: 84	One year	RCT	NR Arterial conduits-to-SVG ratio: 1:1	No difference in overall graft patency (80% vs 81%) p=0.885)	No difference in the composite of death, myocardial infarction, target vessel revascularization and stroke (HR 1.275; 95% CI: 0.391 to 4.160, p=0.674)

Open in a new tab

FU: follow-up; FFR: Fractional flow reserve; iFR: instant wave-free ratio; N: patients included in the study; MI: myocardial infarction; TVR: target vessel revascularization; NR: not reported; RCT: randomized controlled trial; SVG: saphenous vein graft; CABG: coronary artery bypass grafting. A value of p < 0.05 was considered significant in all included studies.

Table 2. Characteristics of the included studies.

Author	Year	N total	N Strategy	Death	MI	TVR	MACE
Moscona et al.¹⁶	2018	109	FFR/iFR-guided: 14 Angiography-guided: 95	FFR/iFR: 1 Angiography: 5	FFR/iFR: 0 Angiography: 2	FFR/iFR: 0 Angiography: 4	FFR/iFR: 1 Angiography: 11
Thuesen et al.¹⁴	2018	97	FFR-guided: 49 Angiography-guided: 48	FFR: 0 Angiography: 2	FFR: 1 Angiography: 0	FFR: 2 Angiography: 0	FFR: 6 Angiography: 6
Rioufol et al.¹⁷	2018	109	FFR-guided: 55 Angiography-guided: 54	FFR: 1 Angiography: 0	NR	NR	HR 0.845 (0.108-6.612)
Fournier et al.¹⁵	2019	627	FFR-guided: 198 Angiography-guided: 429	FFR: 21 Angiography: 79	FFR: 11 Angiography: 34	FFR: 17 Angiography: 27	FFR: 42 Angiography: 113
Toth et al.¹⁹	2019	172	FFR-guided: 88 Angiography-guided: 84	FFR: 3 Angiography: 2	FFR: 0 Angiography: 2	FFR: 2 Angiography: 4	FFR: 5 Angiography: 6

Open in a new tab

MI: myocardial infarction; TVR: target vessel revascularization.

Quantitative synthesis of outcomes

All-cause death.

All-cause death was reported in five studies, which we considered for pooled analysis, for a total of 1,114 patients. The physiology guided strategy has 0.63 times the risk of all-cause death compared to the angiography-guided strategy (RR = 0.63; 95%CI = 0.42–0.96). Figure 2 describes the weighted meta-analysis for all-cause death. The pooled analysis showed negligible heterogeneity among the studies (I2 = 0%; p = 0.55). Under a sensitivity analysis, by recalculating the pooled results of the primary analysis by excluding each single study in turn, in the study by Fournier et al. this risk difference disappears. This effect also disappeared when we limited the analysis to Randomized Controlled Trials (RCTs) (RR = 1.09; 95%CI = 0.28–4.3). Figure 3 describes the weighted meta-analysis for all-cause death when only RCTs were included.

Myocardial infarction.

To analyze the occurrence of MI, four studies that included a total of 1,093 patients were pooled. No significant difference was noted between the two strategies (RR = 0.72; 95%CI = 0.39–1.33) and there was no significant heterogeneity among the studies (I2 = 0%; p = 0.65). The exclusion of any single study and the non-RCTs did not alter the overall combined result.

Target vessel revascularization.

To analyze TVR, four studies that included a total of 1,093 patients were pooled. No significant difference was noted between the two strategies (RR = 1.25; 95%CI = 0.73–2.13) and there was no significant heterogeneity among the studies (I2 = 0%; p = 0.55). The exclusion of any single study and the non-RCTs did not alter the overall combined result.

MACE.

To analyze MACE, five studies that included a total of 1,114 patients were pooled. No significant difference was noted between the two strategies (RR = 0.81; 95%CI = 0.62–1.07) and there was no significant heterogeneity among the studies (I2 = 0%; p = 1). The exclusion of any single study and the non-RCTs did not alter the overall combined result.

Study Bias

The visual inspection of the funnel plot for the outcomes did not reveal any asymmetry among the studies (Figure 4). Further, the Begg's rank correlation test was not statistically significant.

Discussion

Survival has a significant negative correlation with the burden of angiographic obstructive CAD. The SYNTAX score stratifies the angiographic complexity of coronary artery disease and establishes the prognosis of patients with MVD, being an important tool to decide on the best revascularization strategy.^22,23

There are often discordances between the severity of angiography and the physiological significance of CAD, so the functional SYNTAX score, which is obtained by counting only ischemia-provoking lesions, can overcome this limitation. Compared with the classic SYNTAX score, the functional SYNTAX score has better reproducibility and prognostic value, reclassifying up to 32% of CABG candidates, with implications in terms of the therapeutic guidance that this entails.^22-24

Whether or not the favorable impact of coronary physiology on PCI outcomes could be translated to surgical practice became the subject of our investigation.

Our meta-analysis showed a 37% reduction in all-cause death in the group guided by physiology, with a non-statistically significant reduction in MI and MACE; these outcomes were not associated with an increase in TVR. These results must be interpreted within the limitations intrinsic to each of the studies, including selection bias, since this reduction disappears when only RCTs have been pooled for analysis.

When clinical outcomes in revascularization are evaluated, important considerations must be addressed. The first consideration to take into account is related to the (peri) procedural outcomes. The type of MI must be clearly established when comparing strategies, as it is now universally accepted that the prognosis of spontaneous MI is not similar to peri-procedural MI or type 2 MI.^25,26

The natural history of the disease is another important point to consider as a new paradigm focusing on the disease itself (atherosclerosis), rand not on the symptom (ischemia). ^25,27 The composition of the plaque, evaluated by certain imaging features, seems to be the main determinant of prognosis, more than the level of coronary stenosis or its location.^28-30 This may explain the better prognosis associated with complete revascularization in the context of acute coronary syndrome, in which plaques in non-culprit lesions appear to have unstable characteristics, in contrast to what is found in stable coronary disease.³¹

The third important consideration is the type of revascularization. The well-defined benefits of CABG compared with angiography-guided PCI as reported in the ASCERT, SYNTAX, FREEDOM and BEST trials used anatomical and non-functional criteria to guide revascularization and are prior to the newer generation drug-eluting stent technology.^8-12

An important difference between CABG and PCI depends on the protective effects of atherosclerotic disease progression. It is known that most stenoses related to MI are located in the proximal third of the coronary tree. We also know that most MIs arise from non-significant plaques. Surgical bypass grafts are usually implanted distally in the coronary circulation, providing “a collateralization effect” on revascularization, and it seems conceivable that the prognostic benefit of CABG can be explained by protection against coronary events, regardless of the severity of the stenosis of the grafted vessel. The concept of revascularization based on physiology, and not on the type of plaque, eliminates the protective effect of the surgical bypass.^28-30,32

The concept of complete revascularization arose from the early studies on CABG, whereas some publications demonstrated that patients who were completely revascularized experienced a mortality benefit over those who were incompletely revascularized, thus setting the standard for the field of CABG.^33-35

The revascularization based on physiology also raises the concept of complete anatomical vs. functional revascularization. If, on the one hand, the use of coronary physiology reduces the number of grafted vessels, or even surgery, without extracorporeal circulation, on the other hand, it increases the rate of anatomically defined incomplete revascularization.¹⁹

The use of physiology guided revascularization has been shown to reduce the MACE rate in patients with MVD, with the FFR 0.78 cut-off point showing a significant association between the preoperative FFR measurement of the target vessel and the anastomotic functionality at six months. These conclusions are also supported by Botman et al.,³⁶ for whom lesions with FFR> 0.75 are associated with a significant increase in the risk of graft occlusion (p <0.0001).^18,19,36,37

In light of the differences described in susceptibility to competitive flow, it seems likely that the type of conduit used in the FARGO and GRAFFITI trials (in which a large proportion of grafts were SVGs) versus IMPAG (in which only arterial grafts were used) may explain the contradictory results.^14,19,38

The FAME 3 study will compare in a multicenter, randomized fashion FFR-guided PCI with contemporary drug-eluting stents to CABG in patients with 3-vessel coronary artery disease. It will not answer, however, the question of physiology guided CABG compared to angiography-guided CABG.³⁹

Finally, the role of follow-up in this context would also be interesting to consider. The more severe the coronary stenosis, the higher the risk of MI, but it is the non-significant plaques that are responsible for most MIs. We also know that the main cause of death in these patients with CAD is cardiac-related, and that MI is a cause of cardiac death, so therapies that reduce the MI or cardiovascular death will subsequently decrease mortality.³²

We should take the STICH trial as an example, comparing treatment with medical therapy plus CABG and medical therapy alone in patients with CAD and heart failure, with reduced ejection fraction. At five years of follow-up, the intention-to-treat analysis demonstrated no significant difference between the two strategies with respect to the primary outcome of all-cause death. However, after the follow-up period was extended to ten years, a significant reduction in mortality was found for CABG plus medical therapy compared to medical therapy alone (HR, 0.84; 95%CI: 0.73-0.97; p=0.02). Another example is the FAME 2 trial, in which the data published at five years show a strong tendency of lower rates of myocardial infarction in the PCI group (HR 0.66; 95%CI 0.43-1.00; p = 0.049), a difference that was only significant for spontaneous MI (HR 0.62; 95%CI; p = 0.04), not periprocedural MI. Recently, the ISCHEMIA trial showed that, in early follow-up, the primary composite outcome (cardiovascular death, MI, or hospitalization for unstable angina or heart failure) was more frequent in the invasive strategy group than in the conservative strategy group (5.3% vs. 3.4% at six months), due to procedure-related MI's. However, in a posterior follow-up, after about two years, the event curves crossed, and at five years, the incidence of the primary outcome was slightly higher in the conservative strategy group (18.2% and 16.4%). So, it seems that in order to have an impact on hard outcomes, like all-cause death, we have to extend the duration of the observation period.^25,40,41

In our study, the reduction of all-cause death in a context of non-significant reduction of MI and MACE should be interpreted with caution, since this situation could be owed to deaths from non-cardiac causes. It would be interesting not only to assess if these deaths were cardiac-related, but also to extend the follow-up of the studies to observe if the curves of the hard outcomes diverge on longer follow-up periods, allowing to reach definitive conclusions. It should be noted that only the study by Fournier et al.¹⁸ has a follow-up period longer than five years, which can explain the results, since the reduction in the composite endpoint all-cause death or MI supporting a physiology guided strategy was only found when the follow-up was extended.¹⁵

Limitations

The conclusions drawn from this meta-analysis are subjected to the limitations and differences of the original studies included in the analysis. A limitation of this meta-analysis is the presence of trials with small samples and wide-ranging, long-term survival results. Another limitation is represented by an intrinsic selection bias. Several revascularization decisions in the physiology guided strategy were deviated from the functional indication in the included trials, justified by some authors to be related to technical causes and, in some cases, the reluctance to defer revascularization. As aforementioned, as the cause of death was not known, this includes non-cardiac deaths unrelated to the choice of revascularization strategy. Another limitation was that with the inclusion of two retrospective and observational studies, some patients included in this registry might have been treated with physiology guided PCI instead of CABG.

Conclusion

This meta-analysis demonstrates a reduction in all-cause death when a physiology guided CABG strategy was used. Nevertheless, the short follow-up period, small sample size of the included studies and the non-discrimination of the causes of death can largely justify these conclusions. Studies with an extended follow-up observation period are required to reach more robust and definitive conclusions.

Footnotes

Sources of Funding

There were no external funding sources for this study.

Study Association

This study is not associated with any thesis or dissertation work.

Ethics approval and consent to participate

This article does not contain any studies with human participants or animals performed by any of the authors.

[B1] 1.Knuuti J, Wijns W, Saraste A, Capodanno D, Barbato E, Funck-Brentano C, et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes: The Task Force for the diagnosis and management of chronic coronary syndromes of the European Society of Cardiology (ESC) Eur Heart J. 2020;41(3):407–477. doi: 10.1093/eurheartj/ehz425. [DOI] [PubMed] [Google Scholar]; Knuuti J, Wijns W, Saraste A, Capodanno D, Barbato E, Funck-Brentano C, et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes: The Task Force for the diagnosis and management of chronic coronary syndromes of the European Society of Cardiology (ESC). Eur Heart J. 2020;41(3):407-77. [DOI] [PubMed]

[B2] 2.Masdjedi K, Daemen J. Angiography-Based FFR: Reevaluating the Role of the Pressure Wire. Card Interv Today. 2019;13(3):28–33. [Google Scholar]; Masdjedi K, Daemen J. Angiography-Based FFR: Reevaluating the Role of the Pressure Wire. Card Interv Today. 2019;13(3):28-33.

[B3] 3.Morris PD, Curzen N, Gunn JP. Angiography-derived fractional flow reserve: more or less physiology? J Am Heart Assoc. 2020;9(6):e015586. doi: 10.1161/JAHA.119.015586. [DOI] [PMC free article] [PubMed] [Google Scholar]; Morris PD, Curzen N, Gunn JP. Angiography-derived fractional flow reserve: more or less physiology?.J Am Heart Assoc. 2020;9(6):e015586. [DOI] [PMC free article] [PubMed]

[B4] 4.Neumann FJ, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Benedetto U, et al. 2018 ESC/EACTS guidelines on myocardial revascularization. Eur Heart J. 2019;40(2):87–165. [Google Scholar]; Neumann FJ, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Benedetto U, et al. 2018 ESC/EACTS guidelines on myocardial revascularization. Eur Heart J. 2019;40(2):87-165.

[B5] 5.De Bruyne B, Pijls NH, Kalesan B, Barbato E, Tonino PAL, Piroth Z, et al. Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease. N Engl J Med. 2012;367:991–1001. doi: 10.1056/NEJMoa1205361. [DOI] [PubMed] [Google Scholar]; De Bruyne B, Pijls NH, Kalesan B, Barbato E, Tonino PAL, Piroth Z, et al. Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease. N Engl J Med. 2012;367:991-1001. [DOI] [PubMed]

[B6] 6.Pijls NH, Schaardenburgh P, Manoharan G, Boersma E, Bech JW, van’t Veer M, et al. Percutaneous coronary intervention of functionally nonsignificant stenosis: 5-year follow-up of the DEFER study. J Am Coll Cardiol. 2007;49(21):2105–2111. doi: 10.1016/j.jacc.2007.01.087. [DOI] [PubMed] [Google Scholar]; Pijls NH, Schaardenburgh P, Manoharan G, Boersma E, Bech JW, van’t Veer M, et al. Percutaneous coronary intervention of functionally nonsignificant stenosis: 5-year follow-up of the DEFER study. J Am Coll Cardiol. 2007;49(21):2105-11. [DOI] [PubMed]

[B7] 7.Tonino PA, De Bruyne B, Pijls NH, Siebert U, Ikeno F, van’t Veer M, et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med. 2009;360(3):213–224. doi: 10.1056/NEJMoa0807611. [DOI] [PubMed] [Google Scholar]; Tonino PA, De Bruyne B, Pijls NH, Siebert U, Ikeno F, van’t Veer M, et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med. 2009;360(3):213-24. [DOI] [PubMed]

[B8] 8.Weintraub WS, Grau-Sepulveda MV, Weiss JM, O’Brien SM, Peterson ED, Kolm P, et al. Comparative effectiveness of revascularization strategies. N Engl J Med. 2012;366(16):1467–1476. doi: 10.1056/NEJMoa1110717. [DOI] [PMC free article] [PubMed] [Google Scholar]; Weintraub WS, Grau-Sepulveda MV, Weiss JM, O’Brien SM, Peterson ED, Kolm P, et al. Comparative effectiveness of revascularization strategies. N Engl J Med. 2012;366(16):1467-76. [DOI] [PMC free article] [PubMed]

[B9] 9.Serruys PW, Morice MC, Kappetein AP, Colombo A, Holmes DR, Mack MJ, et al. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med. 2009;360(10):961–972. doi: 10.1056/NEJMoa0804626. [DOI] [PubMed] [Google Scholar]; Serruys PW, Morice MC, Kappetein AP, Colombo A, Holmes DR, Mack MJ, et al. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med. 2009;360(10):961-72. [DOI] [PubMed]

[B10] 10.Mohr FW, Morice MC, Kappetein AP, Feldman TE, Ståhle E, Colombo A, et al. Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year follow-up of the randomised, clinical SYNTAX trial. Lancet. 2013;381(9867):629–638. doi: 10.1016/S0140-6736(13)60141-5. [DOI] [PubMed] [Google Scholar]; Mohr FW, Morice MC, Kappetein AP, Feldman TE, Ståhle E, Colombo A, et al. Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year follow-up of the randomised, clinical SYNTAX trial. Lancet. 2013;381(9867):629-38. [DOI] [PubMed]

[B11] 11.Farkouh ME, Domanski M, Sleeper LA, Siami FS, Dangas G, Mack M, et al. Strategies for multivessel revascularization in patients with diabetes. N Engl J Med. 2012;367(25):2375–2384. doi: 10.1056/NEJMoa1211585. [DOI] [PubMed] [Google Scholar]; Farkouh ME, Domanski M, Sleeper LA, Siami FS, Dangas G, Mack M, et al. Strategies for multivessel revascularization in patients with diabetes. N Engl J Med. 2012;367(25):2375-84. [DOI] [PubMed]

[B12] 12.Park SJ, Ahn JM, Kim YH, Park DW, Yun SC, Lee JY, et al. Trial of everolimus-eluting stents or bypass surgery for coronary disease. N Engl J Med. 2015;372(13):1204–1212. doi: 10.1056/NEJMoa1415447. [DOI] [PubMed] [Google Scholar]; Park SJ, Ahn JM, Kim YH, Park DW, Yun SC, Lee JY, et al. Trial of everolimus-eluting stents or bypass surgery for coronary disease. N Engl J Med. 2015;372(13):1204-12. [DOI] [PubMed]

[B13] 13.Toth G, De Bruyne B, Casselman F, De Vroey F, Pyxaras S, Serafino L, et al. Fractional flow reserve-guided versus angiography- guided coronary artery bypass graft surgery. Circulation. 2013;128(13):1405–1411. doi: 10.1161/CIRCULATIONAHA.113.002740. [DOI] [PubMed] [Google Scholar]; Toth G, De Bruyne B, Casselman F, De Vroey F, Pyxaras S, Serafino L, et al. Fractional flow reserve-guided versus angiography- guided coronary artery bypass graft surgery. Circulation. 2013;128(13):1405-11. [DOI] [PubMed]

[B14] 14.Thuesen AL, Riber LP, Veien KT, Christiansen EH, Jensen SE, Modrau I, et al. Fractional flow reserve versus angiographically-guided coronary artery bypass grafting. J Am Coll Cardiol. 2018;72(22):2732–2743. doi: 10.1016/j.jacc.2018.09.043. [DOI] [PubMed] [Google Scholar]; Thuesen AL, Riber LP, Veien KT, Christiansen EH, Jensen SE, Modrau I, et al. Fractional flow reserve versus angiographically-guided coronary artery bypass grafting. J Am Coll Cardiol. 2018;72(22):2732-43. [DOI] [PubMed]

[B15] 15.Fournier S, Toth GG, De Bruyne B, Johnson NP, Ciccarelli G, Xaplanteris P, et al. Six-year follow-up of fractional flow reserve-guided versus angiography-guided coronary artery bypass graft surgery. Circ Cardiovasc Interv. 2018;11(6):e006368. doi: 10.1161/CIRCINTERVENTIONS.117.006368. [DOI] [PubMed] [Google Scholar]; Fournier S, Toth GG, De Bruyne B, Johnson NP, Ciccarelli G, Xaplanteris P, et al. Six-year follow-up of fractional flow reserve-guided versus angiography-guided coronary artery bypass graft surgery. Circ Cardiovasc Interv. 2018;11(6):e006368. [DOI] [PubMed]

[B16] 16.Moscona JC, Stencel JD, Milligan G, Salmon C, Maini R, Katigbak P, et al. Physiologic assessment of moderate coronary lesions: a step towards complete revascularization in coronary artery bypass grafting. Ann Transl Med. 2018;6(15):300–300. doi: 10.21037/atm.2018.06.31. [DOI] [PMC free article] [PubMed] [Google Scholar]; Moscona JC, Stencel JD, Milligan G, Salmon C, Maini R, Katigbak P, et al. Physiologic assessment of moderate coronary lesions: a step towards complete revascularization in coronary artery bypass grafting. Ann Transl Med. 2018;6(15):300. [DOI] [PMC free article] [PubMed]

[B17] 17.Rioufol G. FUTURE trial: Treatment strategy in multivessel coronary disease patients based on fractional flow reserve. Presented at: European Society of Cardiology (ESC) 2018. 2018 Aug 25; Munich, Germany. [Google Scholar]; Rioufol G. FUTURE trial: Treatment strategy in multivessel coronary disease patients based on fractional flow reserve. Presented at: European Society of Cardiology (ESC) 2018. August 25, 2018. Munich, Germany.

[B18] 18.Fournier S, Toth GG, Colaiori I, De Bruyne B, Barbato E. Long-term patency of coronary artery bypass grafts after fractional flow reserve-guided implantation. Circ Cardiovasc Interv. 2019;12(5):e007712. doi: 10.1161/CIRCINTERVENTIONS.118.007712. [DOI] [PubMed] [Google Scholar]; Fournier S, Toth GG, Colaiori I, De Bruyne B, Barbato E. Long-term patency of coronary artery bypass grafts after fractional flow reserve-guided implantation. Circ Cardiovasc Interv. 2019;12(5):e007712. [DOI] [PubMed]

[B19] 19.Toth GG, De Bruyne B, Kala P, Ribichini FL, Casselman F, Ramos R, et al. Graft patency after FFR-guided versus angiography- guided coronary artery bypass grafting. The GRAFFITI trial. EuroIntervention. 2019;15(11):e999–e1005. doi: 10.4244/EIJ-D-19-00463. [DOI] [PubMed] [Google Scholar]; Toth GG, De Bruyne B, Kala P, Ribichini FL, Casselman F, Ramos R, et al. Graft patency after FFR-guided versus angiography- guided coronary artery bypass grafting. The GRAFFITI trial. EuroIntervention. 2019;15(11):e999-1005. [DOI] [PubMed]

[B20] 20.Spadaccio C, Glineur D, Barbato E, Di Franco A, Oldroyd KG, Biondi-Zoccai G, et al. Fractional Flow Reserve-Based Coronary Artery Bypass Surgery: Current Evidence and Future Directions. JACC Cardiovasc Interv. 2020;13(9):1086–1096. doi: 10.1016/j.jcin.2019.12.017. [DOI] [PMC free article] [PubMed] [Google Scholar]; Spadaccio C, Glineur D, Barbato E, Di Franco A, Oldroyd KG, Biondi-Zoccai G, et al. Fractional Flow Reserve-Based Coronary Artery Bypass Surgery: Current Evidence and Future Directions. JACC Cardiovasc Interv. 2020;13(9):1086-96. [DOI] [PMC free article] [PubMed]

[B21] 21.DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177–188. doi: 10.1016/0197-2456(86)90046-2. [DOI] [PubMed] [Google Scholar]; DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177-88. [DOI] [PubMed]

[B22] 22.Serruys PW, Morice MC, Kappetein AP, Colombo A, Holmes DR, Mack MJ, et al. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med. 2009;360(10):961–972. doi: 10.1056/NEJMoa0804626. [DOI] [PubMed] [Google Scholar]; Serruys PW, Morice MC, Kappetein AP, Colombo A, Holmes DR, Mack MJ, et al. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med. 2009;360(10):961-72. [DOI] [PubMed]

[B23] 23.Thuijs DJFM, Kappetein AP, Serruys PW, Mohr FW, Morice MC, Mack MJ, et al. Percutaneous coronary intervention versus coronary artery bypass grafting in patients with three-vessel or left main coronary artery disease: 10-year follow-up of the multicentre randomised controlled SYNTAX trial. Lancet. 2019;394(10206):1325–1334. doi: 10.1016/S0140-6736(19)31997-X. [DOI] [PubMed] [Google Scholar]; Thuijs DJFM, Kappetein AP, Serruys PW, Mohr FW, Morice MC, Mack MJ, et al. Percutaneous coronary intervention versus coronary artery bypass grafting in patients with three-vessel or left main coronary artery disease: 10-year follow-up of the multicentre randomised controlled SYNTAX trial. Lancet. 2019;394(10206):1325-34. [DOI] [PubMed]

[B24] 24.Serruys PW, Kogame N, Katagiri Y, Modolo R, Buszman PE, Íñiguez-Romo A, et al. Clinical outcomes of state-of-the-art percutaneous coronary revascularisation in patients with three-vessel disease: two-year follow-up of the SYNTAX II study. EuroIntervention. 2019;15(3):e244–e252. doi: 10.4244/EIJ-D-18-00980. [DOI] [PubMed] [Google Scholar]; Serruys PW, Kogame N, Katagiri Y, Modolo R, Buszman PE, Íñiguez-Romo A, et al. Clinical outcomes of state-of-the-art percutaneous coronary revascularisation in patients with three-vessel disease: two-year follow-up of the SYNTAX II study. EuroIntervention. 2019;15(3):e244-52. [DOI] [PubMed]

[B25] 25.Maron DJ, Hochman JS, Reynolds HR, Bangalore S, O’Brien SM, Boden WE, et al. Initial Invasive or Conservative Strategy for Stable Coronary Disease. N Engl J Med. 2020;382:1395–1407. doi: 10.1056/NEJMoa1915922. [DOI] [PMC free article] [PubMed] [Google Scholar]; Maron DJ, Hochman JS, Reynolds HR, Bangalore S, O’Brien SM, Boden WE, et al. Initial Invasive or Conservative Strategy for Stable Coronary Disease. N Engl J Med. 2020;382:1395-407. [DOI] [PMC free article] [PubMed]

[B26] 26.Ben-Yehuda O, Chen S, Redfors B, McAndrew T, Crowley A, Kosmidou J, et al. I Impact of large periprocedural myocardial infarction on mortality after percutaneous coronary intervention and coronary artery bypass grafting for left main disease: an analysis from the EXCEL trial. Eur Heart J. 2019;40(24):1930–1941. doi: 10.1093/eurheartj/ehz113. [DOI] [PubMed] [Google Scholar]; Ben-Yehuda O, Chen S, Redfors B, McAndrew T, Crowley A, Kosmidou J, et al. I Impact of large periprocedural myocardial infarction on mortality after percutaneous coronary intervention and coronary artery bypass grafting for left main disease: an analysis from the EXCEL trial. Eur Heart J. 2019;40(24):1930-41. [DOI] [PubMed]

[B27] 27.Lardinois CK. Atherosclerosis - Know your risk -is time for a paradigm shift? US Endocrinol. 2014;10(2):105–110. [Google Scholar]; Lardinois CK. Atherosclerosis - Know your risk -is time for a paradigm shift? US Endocrinol. 2014;10(2):105-10.

[B28] 28.Jeon C, Candia SC, Wang JC, Holper EM, Ammerer M, Kuntz RE, et al. Relative spatial distributions of coronary artery bypass graft insertion and acute thrombosis: a model for protection from acute myocardial infarction. Am Heart J. 2010;160(1):195–201. doi: 10.1016/j.ahj.2010.04.004. [DOI] [PubMed] [Google Scholar]; Jeon C, Candia SC, Wang JC, Holper EM, Ammerer M, Kuntz RE, et al. Relative spatial distributions of coronary artery bypass graft insertion and acute thrombosis: a model for protection from acute myocardial infarction. Am Heart J. 2010;160(1):195-201. [DOI] [PubMed]

[B29] 29.Wang JC, Normand SL, Mauri L, Kuntz RE. Coronary artery spatial distribution of acute myocardial infarction occlusions. Circulation. 2004;110(3):278–284. doi: 10.1161/01.CIR.0000135468.67850.F4. [DOI] [PubMed] [Google Scholar]; Wang JC, Normand SL, Mauri L, Kuntz RE. Coronary artery spatial distribution of acute myocardial infarction occlusions. Circulation. 2004;110(3):278-84. [DOI] [PubMed]

[B30] 30.Mushtaq S, Goncalves P, Garcia-Garcia HM, Pontone G, Bartorelli A, Bertella E, et al. Long-term prognostic effect of coronary atherosclerotic burden: validation of the computed tomography-Leaman score. Circ Cardiovasc Imaging. 2015;8(2):e002332. doi: 10.1161/CIRCIMAGING.114.002332. [DOI] [PubMed] [Google Scholar]; Mushtaq S, Goncalves P, Garcia-Garcia HM, Pontone G, Bartorelli A, Bertella E, et al. Long-term prognostic effect of coronary atherosclerotic burden: validation of the computed tomography-Leaman score. Circ Cardiovasc Imaging. 2015;8(2):e002332. [DOI] [PubMed]

[B31] 31.Al-Abdouh A, Barbarawi M, Bizanti A, Abudaya I, Upadhrasta S, Elias H, et al. Complete revascularization in patients with STEMI and multi-vessel disease: A meta-analysis of randomized controlled trials. Cardiovasc Revasc Med. 2020;21(5):684–691. doi: 10.1016/j.carrev.2020.01.020. [DOI] [PubMed] [Google Scholar]; Al-Abdouh A, Barbarawi M, Bizanti A, Abudaya I, Upadhrasta S, Elias H, et al. Complete revascularization in patients with STEMI and multi-vessel disease: A meta-analysis of randomized controlled trials. Cardiovasc Revasc Med. 2020;21(5):684-91. [DOI] [PubMed]

[B32] 32.Doenst T, Haverich A, Serruys P, Bonow RO, Kappetein P, Falk V, et al. PCI and CABG for treating stable coronary artery disease: JACC Review Topic of the Week. J Am Coll Cardiol. 2019;73(8):964–976. doi: 10.1016/j.jacc.2018.11.053. [DOI] [PubMed] [Google Scholar]; Doenst T, Haverich A, Serruys P, Bonow RO, Kappetein P, Falk V, et al. PCI and CABG for treating stable coronary artery disease: JACC Review Topic of the Week. J Am Coll Cardiol. 2019;73(8):964-76. [DOI] [PubMed]

[B33] 33.Buda AJ, Macdonald IL, Anderson MJ, Strauss HD, David TE, Berman ND. Long-term results following coronary bypass operation. Importance of preoperative actors and complete revascularization. J Thorac Cardiovasc Surg. 1981;82(3):383–390. [PubMed] [Google Scholar]; Buda AJ, Macdonald IL, Anderson MJ, Strauss HD, David TE, Berman ND. Long-term results following coronary bypass operation. Importance of preoperative actors and complete revascularization. J Thorac Cardiovasc Surg. 1981;82(3):383-90. [PubMed]

[B34] 34.Bell MR, Gersh BJ, Schaff HV, Holmes DR, Jr, Fisher LD, Alderman EL, et al. Effect of completeness of revascularization on long-term outcome of patients with three-vessel disease undergoing coronary artery bypass surgery. A report from the Coronary Artery Surgery Study (CASS) Registry. Circulation. 1992;86(2):446–457. doi: 10.1161/01.cir.86.2.446. [DOI] [PubMed] [Google Scholar]; Bell MR, Gersh BJ, Schaff HV, Holmes Jr DR, Fisher LD, Alderman EL, et al. Effect of completeness of revascularization on long-term outcome of patients with three-vessel disease undergoing coronary artery bypass surgery. A report from the Coronary Artery Surgery Study (CASS) Registry. Circulation. 1992;86(2):446-57. [DOI] [PubMed]

[B35] 35.Ong AT, Serruys PW. Complete revascularization: coronary artery bypass graft surgery versus percutaneous coronary intervention. Circulation. 2006;114(3):249–255. doi: 10.1161/CIRCULATIONAHA.106.614420. [DOI] [PubMed] [Google Scholar]; Ong AT, Serruys PW. Complete revascularization: coronary artery bypass graft surgery versus percutaneous coronary intervention. Circulation. 2006;114(3):249-55. [DOI] [PubMed]

[B36] 36.Botman K, Pijls NH, Bech JW, Aarnoudse W, Peels K, Straten BV, et al. Percutaneous coronary intervention or bypass surgery in multivessel disease? A tailored approach based on coronary pressure measurement. Catheter Cardiovasc Interv. 2004;63(2):184–191. doi: 10.1002/ccd.20175. [DOI] [PubMed] [Google Scholar]; Botman K, Pijls NH, Bech JW, Aarnoudse W, Peels K, Straten BV, et al. Percutaneous coronary intervention or bypass surgery in multivessel disease? A tailored approach based on coronary pressure measurement. Catheter Cardiovasc Interv. 2004;63(2):184-91. [DOI] [PubMed]

[B37] 37.Kern MJ, Seto AH. High FFR strongly predicts arterial graft dysfunction: pure benefit in a pure population? Eur Heart J. 2019;40(29):2429–2431. doi: 10.1093/eurheartj/ehz371. [DOI] [PubMed] [Google Scholar]; Kern MJ, Seto AH. High FFR strongly predicts arterial graft dysfunction: pure benefit in a pure population? Eur Heart J. 2019;40(29):2429-31. [DOI] [PubMed]

[B38] 38.Glineur D, Grau JB, Etienne PY, Benedetto U, Fortier JH, Papadatos S, et al. Impact of preoperative fractional flow reserve on arterial bypass graft anastomotic function: the IMPAG trial. Eur Heart J. 2019;40(29):2421–2428. doi: 10.1093/eurheartj/ehz329. [DOI] [PubMed] [Google Scholar]; Glineur D, Grau JB, Etienne PY, Benedetto U, Fortier JH, Papadatos S, et al. Impact of preoperative fractional flow reserve on arterial bypass graft anastomotic function: the IMPAG trial. Eur Heart J. 2019;40(29):2421-28. [DOI] [PubMed]

[B39] 39.Zimmermann FM, De Bruyne B, Pijls NH, Desai M, Oldroyd KG, Park SJ, et al. Rationale and design of the Fractional Flow Reserve versus Angiography for Multivessel Evaluation (FAME) 3 Trial: a comparison of fractional flow reserve-guided percut aneous coronary intervention and coronary artery bypass graft surgery in patients with multivessel coronary artery disease. Am Heart J. 2015;170(4):619.e2–626.e2. doi: 10.1016/j.ahj.2015.06.024. [DOI] [PubMed] [Google Scholar]; Zimmermann FM, De Bruyne B, Pijls NH, Desai M, Oldroyd KG, Park SJ, et al. Rationale and design of the Fractional Flow Reserve versus Angiography for Multivessel Evaluation (FAME) 3 Trial: a comparison of fractional flow reserve-guided percut aneous coronary intervention and coronary artery bypass graft surgery in patients with multivessel coronary artery disease. Am Heart J. 2015;170(4):619-26.e2. [DOI] [PubMed]

[B40] 40.Petrie MC, Jhund PS, She L, Adlbrecht C, Doenst T, Panza JA, et al. Ten-Year Outcomes After Coronary Artery Bypass Grafting According to Age in Patients With Heart Failure and Left Ventricular Systolic Dysfunction: An Analysis of the Extended Follow-Up of the STICH Trial (Surgical Treatment for Ischemic Heart Failure) Circulation. 2016;134(18):1314–1324. doi: 10.1161/CIRCULATIONAHA.116.024800. [DOI] [PMC free article] [PubMed] [Google Scholar]; Petrie MC, Jhund PS, She L, Adlbrecht C, Doenst T, Panza JA, et al. Ten-Year Outcomes After Coronary Artery Bypass Grafting According to Age in Patients With Heart Failure and Left Ventricular Systolic Dysfunction: An Analysis of the Extended Follow-Up of the STICH Trial (Surgical Treatment for Ischemic Heart Failure). Circulation. 2016;134(18):1314-24. [DOI] [PMC free article] [PubMed]

[B41] 41.Xaplanteris P, Fournier S, Pijls NHJ, Fearon WF, Barbato E, Tonino PAL, et al. Five- year outcomes with PCI guided by fractional flow reserve. N Engl J Med. 2018;379(3):250–259. doi: 10.1056/NEJMoa1803538. [DOI] [PubMed] [Google Scholar]; Xaplanteris P, Fournier S, Pijls NHJ, Fearon WF, Barbato E, Tonino PAL, et al. Five- year outcomes with PCI guided by fractional flow reserve. N Engl J Med. 2018;379(3):250-9. [DOI] [PubMed]

PERMALINK

Enxerto de Bypass de Artéria Coronária Guiado por Angiografia ou Fisiologia: Uma Metanálise

José Martins

Vera Afreixo

Luís Santos

Luís Fernandes

Ana Briosa

Resumo

Fundamento:

Objetivos:

Métodos:

Resultados:

Conclusão:

Introdução

Métodos

Fontes de dados e buscas

Seleção dos estudos

Figura 1. Fluxo dos estudos incluídos na metanálise.

Desfechos

Análise estatística

Resultados

Identificação do Estudo

Características dos estudos incluídos

Tabela 1. Características dos estudos incluídos.

Tabela 2. Características dos estudos incluídos.

Síntese quantitativa dos desfechos

Morte por todas as causas.

Figura 2. Gráfico em Floresta da razão de risco agrupada pelos desfechos: (A) morte por todas as causas; (B) IM; (C) TVR; (D) MACE. O tamanho dos marcadores de dados indica o peso do estudo. IC: intervalo de confiança; IM: infarto do miocárdio; TVR: revascularização do vaso alvo.

Infarto do miocárdio.

Revascularização do vaso alvo.

MACE.

Viés do estudo

Discussão

Limitações

Conclusão

Footnotes

Referências

Physiology or Angiography-Guided Coronary Artery Bypass Grafting: A Meta-Analysis

José Martins

Vera Afreixo

Luís Santos

Luís Fernandes

Ana Briosa

Abstract

Background:

Objectives:

Methods:

Results:

Conclusion:

Introduction

Methods

Data sources and searches

Study selection

Figure 1. Flow chart of studies included in the meta-analysis.

Endpoints

Statistical analysis

Results

Study identification

Characteristics of the included studies

Table 1. Characteristics of the included studies.

Table 2. Characteristics of the included studies.

Quantitative synthesis of outcomes

All-cause death.

Figure 2. Forest plot of the pooled risk ratio for the outcomes: (A) all cause death; (B) MI; (C) TVR; (D) MACE. The sizes of data markers indicate the weight of the study. CI: confidence interval; MI: myocardial infarction; TVR: target vessel revascularization.

Figure 3. Forest plot of the pooled risk ratio for the outcomes when only RCTs were included: (A) all-cause death; (B) MI; (C) TVR; (D) MACE. The sizes of data markers indicate the weight of the study. CI: confidence interval; MI: myocardial infarction; TVR: target vessel revascularization.

Myocardial infarction.

Target vessel revascularization.

MACE.

Study Bias

Discussion

Limitations

Conclusion

Footnotes

ACTIONS

PERMALINK

RESOURCES

Similar articles

Cited by other articles

Links to NCBI Databases