Arq Bras Cardiol abc Arquivos Brasileiros de Cardiologia Arq. Bras. Cardiol. 0066-782X 1678-4170 Sociedade Brasileira de Cardiologia - SBC t7KLbgWD3LPtGyxjXKHhRtr S0066-782X2025001000305 00305 10.36660/abc.20250069 Artigo Original Balões Revestidos com Paclitaxel versus Stents Farmacológicos na Doença Arterial Coronariana de Pequenos Vasos: Revisão Sistemática e Metanálise 0000-0002-7329-5060 Gobbo Marília Oberto da Silva Concepção e desenho da pesquisa Obtenção de dados Análise e interpretação dos dados Redação do manuscrito 1 Sudo Renan Yuji Ura Análise e interpretação dos dados Análise estatística Redação do manuscrito 2 Franco Ancy Jenil Obtenção de dados Análise e interpretação dos dados Redação do manuscrito Revisão crítica do manuscrito quanto ao conteúdo 3 Pereira Mable Obtenção de dados Análise e interpretação dos dados Redação do manuscrito 4 Milbradt Tanize Louize Concepção e desenho da pesquisa Obtenção de dados Análise e interpretação dos dados Redação do manuscrito 5 Bakir Zeynep Eylul Obtenção de dados Análise e interpretação dos dados Redação do manuscrito 6 Pires Iago Zang Obtenção de dados Análise e interpretação dos dados Redação do manuscrito 1 Akinfenwa Stephen Redação do manuscrito Revisão crítica do manuscrito quanto ao conteúdo 7 0000-0002-3668-9976 Agostini Gustavo Luís Análise e interpretação dos dados Redação do manuscrito Revisão crítica do manuscrito quanto ao conteúdo 8 0000-0002-4207-5364 Pellegrini Denise Análise e interpretação dos dados Redação do manuscrito Revisão crítica do manuscrito quanto ao conteúdo 9 0000-0002-7895-8281 Caramori Paulo R. A. Revisão crítica do manuscrito quanto ao conteúdo 9 Pontifícia Universidade Católica do Rio Grande do Sul Porto Alegre RS Brasil Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS – Brasil Universidade Federal da Grande Dourados Dourados MS Brasil Universidade Federal da Grande Dourados, Dourados, MS – Brasil McLaren Bay Region Internal Medicine Department Bay City Michigan EUA McLaren Bay Region, Internal Medicine Department, Bay City, Michigan – EUA Lincoln American University School of Medicine Georgetown Guiana Lincoln American University School of Medicine, Georgetown – Guiana Universidade Federal de Santa Maria Santa Maria RS Brasil Universidade Federal de Santa Maria, Santa Maria, RS – Brasil University of Rome La Sapienza Rome Lazio Itália University of Rome La Sapienza, Rome, Lazio – Itália University of Connecticut Storrs EUA University of Connecticut, Storrs – EUA Tacchini Hospital Bento Gonçalves RS Brasil Tacchini Hospital, Bento Gonçalves, RS – Brasil Hospital São Lucas PUCRS Porto Alegre RS Brasil Hospital São Lucas da PUCRS, Porto Alegre, RS – Brasil Paulo R. A. Caramori Hospital São Lucas da PUCRS – Av. Ipiranga 6690 – Sala 300. CEP 90610-000, Porto Alegre, RS – Brasil E-mail: caramori@cardiarte.com.br

Henrique Ribeiro

Não há conflito com o presente artigo

 15 12 2025 11 2025 122 10 e20250069 30 01 2025 08 07 2025 28 07 2025 Este é um artigo de acesso aberto distribuído sob os termos da licença de atribuição pelo Creative Commons Resumo Fundamento

Os stents farmacológicos (SF) permanecem como padrão terapêutico na intervenção coronariana percutânea em casos de doença arterial coronariana de pequenos vasos (DACPV). Balões revestidos com paclitaxel (BRP) têm surgido como alternativa promissora, com estudos recentes indicando desfechos favoráveis em curto e médio prazos, embora a maioria apresente limitações quanto ao tamanho amostral.

 Objetivo

Comparar os desfechos clínicos e angiográficos entre SF e BRP em pacientes com DACPV.

 Métodos

Foram realizadas buscas nas bases de dados PubMed, Embase, Cochrane Library e ClinicalTrials.gov por estudos que comparassem BRP e SF em DACPV, definida como diâmetro de referência do vaso < 3,0 mm. Realizou-se metanálise com modelo de efeitos aleatórios, apresentando os resultados como diferença média (DM) ou razão de risco (RR). A significância estatística foi considerada para p < 0,05. A heterogeneidade foi avaliada por meio dos testes qui-quadrado, Tau e Tau2. O protocolo da revisão foi registrado na PROSPERO (CRD42024506502).

 Resultados

Foram incluídos 12 estudos, totalizando 17.441 pacientes (média de idade entre 58 e 73 anos), com follow-up clínico variando entre 8 e 36 meses. Todos os estudos avaliaram BRP. Não foram observadas diferenças significativas entre BRP e SF em relação à revascularização da lesão-alvo (RR, 1,24; IC 95%, 0,82-1,85; p = 0,30), perda tardia de lúmen (DM, –0,09 mm; IC 95%, –0,41 a 0,23; p = 0,57), eventos cardiovasculares adversos maiores (RR, 1,01; IC 95%, 0,76-1,33; p = 0,95), mortalidade por todas as causas (RR, 0,81; IC 95%, 0,50-1,31; p = 0,39), mortalidade cardiovascular (RR, 1,74; IC 95%, 0,78-3,89; p = 0,17) e infarto do miocárdio (RR, 0,76; IC 95%, 0,46-1,27; p = 0,30).

 Conclusões

A angioplastia com BRP apresentou desfechos clínicos e angiográficos comparáveis aos observados com SF na DACPV, reforçando sua viabilidade como alternativa segura e eficaz em pacientes selecionados.

Paclitaxel-Coated Balloons versus Drug-Eluting Stents in Small Vessel Coronary Artery Disease: A Systematic Review and Meta-Analysis DES: drug-eluting stent; MACE: major adverse cardiovascular events; MI: myocardial infarction; PCB: paclitaxel-coated balloon; SVD: small vessel disease; TLR: target lesion revascularization.

Palavras-chave: Stents Farmacológicos Doença da Artéria Coronariana Intervenção Coronária Percutânea Fontes de financiamento: O presente estudo não teve fontes de financiamento externas. Introdução

A doença arterial coronariana de pequenos vasos (DACPV) é comum em pacientes submetidos à intervenção coronariana percutânea (ICP), representando até 50% de todos os procedimentos realizados anualmente.1 O tratamento da DACPV com stents farmacológicos (SF) apresenta desafios específicos, incluindo maior risco de dissecção, ruptura do vaso e reestenose, além da necessidade de terapia antiplaquetária dupla (TAD) prolongada após a implantação do stent.2

Embora os SF tenham demonstrado superioridade em relação à angioplastia com balão convencional, os balões farmacológicos (BF) surgiram como alternativa promissora em contextos anatômicos específicos, como na DACPV.3 Os BF consistem em cateteres-balão revestidos com agentes antiproliferativos — geralmente paclitaxel, sirolimus ou análogos limus — liberados na parede do vaso durante a insuflação do balão.4 A insuflação costuma durar 30-60 segundos. Essa estratégia evita a implantação de material estranho permanente, o que pode reduzir reações inflamatórias tardias e diminuir o risco de reestenose e trombose. A ausência de arcabouço metálico e polímero durável contribui para a preservação da anatomia vascular e da função vasomotora, minimizando distúrbios hemodinâmicos e, potencialmente, reduzindo a necessidade de TAD prolongada.5

O paclitaxel é citotóxico, mas atinge concentrações citotóxicas na parede do vaso apenas nas primeiras horas após a aplicação do BF. Posteriormente, sua ação se assemelha à do sirolimus. Devido à sua alta lipofilicidade, o paclitaxel apresenta maior retenção na parede vascular, proporcionando inibição mais sustentada da proliferação neointimal em comparação aos fármacos à base de limus. Isso pode conferir uma vantagem a longo prazo aos balões revestidos com paclitaxel (BRP) em relação aos dispositivos revestidos com sirolimus.6,7

Apesar do consenso entre especialistas quanto à viabilidade da angioplastia com BF como alternativa aos SF na DACPV, as evidências oriundas de ensaios clínicos randomizados (ECRs) ainda são limitadas, principalmente em razão do pequeno tamanho amostral.8-11 Diante disso, realizamos uma revisão sistemática e metanálise para sintetizar os dados disponíveis que comparam os desfechos clínicos dessas duas estratégias terapêuticas.

 Métodos Critérios de elegibilidade

Foram considerados elegíveis os estudos que atendessem aos seguintes critérios: ECRs ou estudos de coorte não randomizados; estratégias de ICP envolvendo BFs ou SFs; e inclusão de pacientes com DACPV (diâmetro de referência do vaso < 3,0 mm). Os estudos foram incluídos apenas se relatassem pelo menos um desfecho clínico relevante.

Foram excluídos estudos com comparadores inadequados, diâmetro de vaso de referência ≥ 3 mm, follow-up inferior a 6 meses, texto completo indisponível ou publicações em idiomas diferentes do inglês.

 Estratégia de busca e extração de dados

Esta revisão sistemática e metanálise seguiu as recomendações da Cochrane Collaboration e foi relatada conforme os itens do Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) (Tabela S1).12,13 O protocolo da revisão foi prospectivamente registrado na base PROSPERO em 25 de janeiro de 2024 sob o código CRD42024506502.

As buscas foram conduzidas por dois revisores nas bases PubMed, Embase e Cochrane Library, desde suas criações até janeiro de 2024, utilizando os termos drug-coated balloon, drug-eluting stent e coronary small vessel. A estratégia completa de busca está disponível no material suplementar. As listas de referências também foram examinadas em busca de estudos relevantes. O banco ClinicalTrials.gov foi consultado para identificar ensaios adicionais não recuperados na busca principal.

As características dos estudos, dados basais e desfechos clínicos foram extraídos de forma independente por 4 revisores, seguindo critérios predefinidos e avaliações de qualidade. As divergências foram resolvidas por meio de discussão com outros 2 revisores, e, quando necessário, com a participação dos revisores seniores.

 Desfechos e subanálises

O desfecho primário foi a incidência de RLA motivada por critérios clínicos, no maior tempo de follow-up disponível. O principal desfecho angiográfico secundário foi a PTL. Outros desfechos de interesse incluíram eventos cardiovasculares adversos maiores (ECAM), mortalidade por todas as causas, mortalidade cardiovascular (CV) e infarto agudo do miocárdio (IAM). Os dados detalhados dos desfechos de cada estudo estão apresentados no Material Suplementar (Tabela S2).

 Avaliação da qualidade

Os estudos de coorte não randomizados foram avaliados utilizando a Newcastle-Ottawa Scale (NOS).14 Essa ferramenta atribui até 9 estrelas com base em 3 domínios: seleção dos participantes, comparabilidade dos grupos e determinação dos desfechos (Tabela S3). Os ECRs foram avaliados por meio da ferramenta Cochrane Risk of Bias 2.0 (RoB 2), que classifica os estudos como de “baixo risco de viés”, “algumas preocupações” ou “alto risco de viés” em 5 domínios: processo de randomização, desvios das intervenções planejadas, dados ausentes dos desfechos, mensuração dos desfechos e seleção dos resultados relatados (Figura S4).15

A certeza da evidência foi avaliada por 2 revisores independentes (R.S. e M.G.) utilizando o sistema GRADE (Grading of Recommendations, Assessment, Development and Evaluation), com níveis que variam de alta a muito baixa (Tabela S5).16 A presença de viés de publicação foi explorada por meio de análise gráfica em funil com estimativas pontuais ponderadas pelo tamanho dos estudos e teste de Egger.

 Análise estatística

Os dados foram sintetizados por meio de metanálise com modelo de efeitos aleatórios, utilizando o estimador de máxima verossimilhança restrita. Esse modelo foi escolhido para considerar possíveis heterogeneidades clínicas, metodológicas e estatísticas, reconhecendo que o verdadeiro efeito da intervenção pode variar entre os estudos.17,18 Os desfechos dicotômicos foram expressos como razões de risco (RR) e os desfechos contínuos como diferenças médias (DM). Análises de subgrupos compararam os desfechos entre ECRs e estudos observacionais, levando em conta possíveis interações qualitativas e quantitativas. A significância estatística foi definida por um IC 95% e valor de p < 0,05. A heterogeneidade foi avaliada pelos testes qui-quadrado, Tau e Tau2. Para evitar interpretações equivocadas decorrentes de um limiar fixo para o I2, a heterogeneidade também foi analisada em relação ao intervalo de predição (PI).18,19 Todas as análises estatísticas foram realizadas no software R, versão 4.4.1 (R Foundation for Statistical Computing).20

 Resultados Estratégia de busca e características basais dos estudos incluídos

A busca inicial identificou 566 registros. Após a remoção de 236 duplicatas, 312 artigos foram excluídos com base no título e resumo (Figura 1). Um total de 18 artigos foi submetido à avaliação do texto completo. Destes, 2 foram excluídos por indisponibilidade do texto completo, 1 por utilizar comparador inadequado e 3 por incluir pacientes com diâmetro de vaso de referência ≥ 3 mm. Foram incluídos 12 estudos, totalizando 17.441 pacientes com DACPV.21-32 As publicações ocorreram entre 2010 e 2024, com follow-up médio variando entre 8 e 36 meses. Todos os BFs utilizados eram revestidos com paclitaxel. Os nomes comerciais dos BRPs e dos SFs utilizados nos estudos individuais estão listados no Material Suplementar (Tabela S6).

– Fluxograma PRISMA para identificação, triagem e inclusão dos estudos. PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

As características dos estudos e intervenções incluídos estão resumidas nas Tabelas 1 e 2. Na linha de base, a população era predominantemente masculina, com média de idade de 64 anos e alta prevalência de diabetes e hipertensão. O diâmetro médio do vaso de referência foi de 2,19 mm. A artéria descendente anterior esquerda foi o local mais comum das lesões-alvo. Quase metade dos pacientes apresentava doença multivascular. A fração de ejeção do ventrículo esquerdo (FEVE) não foi relatada na metade dos estudos; nos estudos que forneceram esses dados, os valores da FEVE estavam dentro da faixa compatível com FE preservada.

– Características clínicas basais dos estudos incluídos
Estudo/Característica Cortese, et al., 201021 Latib, et al., 201222 Sinaga, et al., 201627 Giannini, et al., 201723 Jeger, et al., 201828 Sim, et al., 201824 Tang, et al., 201829 Cortese, et aI., 202031 Silverio, et al., 202030 Tsai, et al., 202226 Kawai, et al., 202225 Liu, et al., 202432
Tamanho da amostra, n 28/29 90/92 172/163 90/91 382/376 87/200 116/110 118/114 1154/13634 47/59 19/23 129/118
Tipo de estudo RCT RCT Coorte retrospectiva Coorte retrospectiva ECR Coorte retrospectiva ECR ECR Coorte prospectiva Coorte retrospectiva ECR ECR
Follow-up clínico, meses 9 24 12 12 12 12 12 12 36 12 8 12
Idade, anos 68/67 65/66 61/61 65/66 67/68 58/61 60/60 64/66 68/69 65 69/73 60/60
Sexo masculino, % 79/76 80/77 77/72 80/78 77/70 81/77 77/77 77/70 70/66 83/81 79/74 73/70
Diabetes, % 46/37 43/38 51/49 43/40 32/34 63/54 39/43 38/35 35/38 49/54 26/34 35/38
Hiperlipidemia, % 60/45 78/79 70/72 79/78 68/69 80/76 52/50 60/55 59/50 85/71 79/82 45/54
Hipertensão, % 75/69 80/81 72/69 78/81 84/88 79/68 67/78 65/66 68/64 93/83 89/91 73/75
Tabagismo atual, % NA 16/10 30/44 43/33 21/19 48/29 29/32 19/16 12/16 44/35 52/52 21/21
IAM prévio, % 17/20 51/35 28/27 51/58 41/35 56/57 22/25 28/39 31/24 10/11 10/21 25/22
DAC estável, % 46/44 75/78 22/34 75/81 70/73 NA 31/30 53/56 32/23 87/81 100/100 20/25
Angina instável, % 53/55 24/21 49/38 24/18 12/11 NA 69/73 15/15 11/10 12/18 0 63/65
IAMSSST 0 0 — 0 13/14 35/30 0 19/22 41/43 — 0 0
IAMCST 0 0 28/27 0 3/1 20/27 0 10/7 14/23 NA 0 0
FEVE, % NA NA NA NA 60/60 NA 60/60 58/58 NA 58/59 67/66 62/61
Doença multiarterial, % 60/65 62/60 NA 61/71 82/75 72/78 41/41 72/75 37/49 NA 0/0 0/0.8

Os valores são apresentados como médias, salvo indicação em contrário. O nível de significância estatística adotado nos estudos incluídos foi de 5%, quando disponível nas publicações originais. DAC: doença arterial coronariana; ECR: ensaio clínico randomizado; FEVE: fração de ejeção do ventrículo esquerdo; IAM: infarto agudo do miocárdio; IAMCST: IAM com supradesnivelamento do segmento ST; IAMSSST: IAM sem supradesnivelamento do segmento ST; NA: não aplicável.

– Características angiográficas e procedimentais basais dos estudos incluídos
Estudo/Característica Cortese, et al., 201021 Latib, et al., 201222 Sinaga, et al., 201627 Giannini, et al., 201723 Jeger, et al., 201828 Sim, et al., 201824 Tang, et al., 201829 Cortese, et aI., 202031 Silverio, et al., 202030 Tsai, et al., 202226 Kawai, et al., 202225 Liu, et al., 202432
Tamanho da amostra, n 28/29 90/92 172/163 90/91 382/376 87/200 116/110 118/114 1154/13634 47/59 19/23 129/118
Follow-up angiográfico, meses 6 24 12 12 12 12 9 6 36 12 8 9
Artéria descendente anterior esquerda, % 54/52 11/11 41/41 11/17 34/31 NA 10/10 39/40 49/45 42/44 42/17 22/23
Artéria diagonal, % NA 17/8 NA 17/16 NA NA 14/15 NA NA NA NA NA
Artéria circunflexa esquerda, % 18/10 11/16 32/34 11/13 47/49 NA 59/47 31/37 35/32 36/43 26/61 52/48
Tronco da coronária esquerda, % NA NA NA NA NA NA NA NA 0.4/0.5 NA NA NA
Artéria marginal obtusa, % NA 27/32 NA 27/18 NA NA 4/6 NA NA NA NA NA
Artéria coronária direita, % 28/38 8/9 26/23 8/11 20/20 NA 9/10 30/23 15/22 22/13 32/22 26/29
Artéria descendente posterior/posterolateral, % NA 27/22 NA 27/20 NA NA 20/26 NA NA NA NA NA
Comprimento da lesão, mm 12,4/11,3 15,4/14,4 NA NA NA 18,5/20,3 10,5/10,8 13,5/14 NA 19,8/20 11,8/11,3 12,3/11,5
Estenose do diâmetro, % 86/89 82/83 NA 82/82 NA 88/90 70/71 75/76 NA 87/86 68/60 69/71
Diâmetro mínimo do lúmen, mm 0,48/0,40 NA NA NA NA 0,20/0,19 0,64/0,65 0,82/0,83 NA 0,29/0,29 0,75/0,80 0,68/0,65
Diâmetro de referência do vaso, mm 2,45/2,36 2,41/2,41 2,22/2,44 2,49/2,5 NA 1,88/1,95 2,42/2,42 2,23/2,18 2,23/2,18 2,1/2,1 2,29/2,08 2,2/2,21
Pressão do dispositivo, ATM 7,7/13,4 9,6/17,2 NA 9,6/17,8 11,1/13,6 NA 9,1/10,7 13,7/11,4 10/18 NA 7,7/13 10,2/10,8
Diâmetro do dispositivo, mm 2,48/2,54 2,49/2,49 2,25/2,5 2,49/2,5 2,75/2,57 NA 2,41/2,41 NA 2,5/2,5 2,09/2,18 2,6/2,4 2,44/2,42
Comprimento do dispositivo, mm 18,6/18,9 25,6/18,5 20,2/22,2 25,6/27,1 23,9/23,1 NA 21/20,4 21,8/18,3 20/18 26/25 19/17 20,5/19,4

Os valores são apresentados como números absolutos (n) ou percentuais (%). O nível de significância estatística adotado nos estudos incluídos foi de 5%, quando disponível nas publicações originais. ATM: atmosferas.

 Desfechos

Em um follow-up médio de 32,4 meses, não foram observadas diferenças estatisticamente significativas entre os BFs e os SFs para nenhum dos desfechos analisados. O desfecho primário, RLA, ocorreu em 6,6% dos pacientes do grupo BF em comparação a 5,3% no grupo SF (RR, 1,24; IC 95%, 0,82-1,85; Figura 2A). O desfecho angiográfico secundário, PTL, também foi semelhante entre os grupos (DM, –0,09 mm; IC 95%, –0,41 a 0,23), com valores médios de 0,17 mm no grupo BF e 0,16 mm no grupo SF (Figura 2B). Outros desfechos angiográficos não apresentaram diferenças significativas e estão descritos nas Figuras Suplementares S7A e S7B.

– Comparação da Revascularização da Lesão-Alvo e da Perda Tardia do Lúmen entre Balões Revestidos com Paclitaxel e Stents Liberadores de Fármacos em Doença de Pequenos Vasos. BF: balão farmacológico; BRP: balão revestido com paclitaxel; DM: diferença média; g.l.: graus de liberdade; IC 95%: intervalo de confiança de 95%; IP: intervalo de predição; PTL: perda tardia de lúmen; RLA: revascularização da lesão-alvo; RR: razão de risco; SF: stent farmacológico.

Os desfechos clínicos também não diferiram significativamente entre os grupos. A RR para ECAM foi de 1,01 (IC 95%, 0,76-1,33; Figura 3A); para mortalidade por todas as causas, 0,81 (IC 95%, 0,50-1,30; Figura 3B); para mortalidade CV, 1,74 (IC 95%, 0,78-3,89; p = 0,17; I2 = 0%; PI = 0,01-323,77; Figura S8); e para IAM, 0,76 (IC 95%, 0,46-1,27; Figura 3C). A Ilustração Central resume os principais achados da revisão.

– Comparação de Eventos Cardiovasculares Adversos Maiores, Mortalidade por Todas as Causas e Infarto do Miocárdio entre Balões Revestidos com Paclitaxel e Stents Liberadores de Fármacos em Doença de Pequenos Vasos. BF: balão farmacológico; BRP: balão revestido com paclitaxel; DM: diferença média; ECAM: eventos cardiovasculares adversos maiores; ECR: ensaio clínico randomizado; g.l.: graus de liberdade; IC 95%: intervalo de confiança de 95%; IP: intervalo de predição; PTL: perda tardia de lúmen; RLA: revascularização da lesão-alvo; RR: razão de risco; SF: stent farmacológico.

As análises de subgrupos por delineamento dos estudos (ECRs vs. estudos de coorte não randomizados) apresentaram resultados consistentes.

 Avaliação da qualidade e certeza da evidência

O risco de viés nos ECRs e nos estudos de coorte não randomizados incluídos nesta metanálise foi considerado baixo (Tabela S4).

A análise gráfica em funil do desfecho ECAM, utilizada para avaliar viés de publicação por inspeção visual de assimetria, sugeriu um viés favorável aos benefícios dos BF (Figura 4). No entanto, o teste de Egger não apresentou significância estatística para viés de publicação. O GRADE encontra-se no Material Suplementar (Tabela S5).

– Análise de gráfico em funil do desfecho de eventos cardiovasculares adversos maiores. RR: razão de risco.

Discussão

Esta revisão sistemática e metanálise que comparou BRP e SF na DACPV incluiu 12 estudos, abrangendo 17.441 pacientes, com follow-up variando de 8 a 36 meses (média de 32,4 meses). Não foram observadas diferenças significativas no desfecho primário, RLA motivada por critérios clínicos, nem nos desfechos secundários, como PTL, ECAM, mortalidade por todas as causas, mortalidade CV e IAM. Esses achados sustentam a segurança e eficácia dos BRP como alternativa viável aos SF no tratamento da DACPV. A consistência dos resultados entre os estudos, inclusive aqueles com BF de nova geração, reforça ainda mais essa evidência.

Nossa análise agrupada destacou uma alta prevalência de fatores de risco CV, com mais da metade dos pacientes apresentando hipertensão e mais de um terço com diabetes, refletindo uma população real submetida à ICP para DACPV.

O maior estudo incluído, o BASKET-SMALL 2 (Basel Stent Kosten Effektivitäts Trial Drug Eluting Balloons vs Drug Eluting Stents in Small Vessel Interventions),28 incluiu pacientes com pré-dilatação bem-sucedida da lesão e não encontrou diferença significativa em ECAM aos 12 meses entre os grupos BF e SF (7,3% vs. 7,5%; hazard ratio, 0,97; IC 95%, 0,58-1,64; p = 0,92), bem como taxas semelhantes de morte cardíaca, IAM e revascularização do vaso-alvo. Em contraste, o estudo PICCOLETO II (Drug Eluting Balloon Efficacy for Small Coronary Vessel Disease Treatment)31 demonstrou superioridade do BF sobre o SF quanto à PTL na lesão, aos 6 meses. O follow-up prolongado mostrou taxas semelhantes de mortalidade e IAM, porém maiores taxas de ECAM e oclusão aguda do vaso no grupo SF (20,8% vs. 10,8%, p = 0,046; e 4% vs. 0%, p = 0,042, respectivamente).33 Já o estudo REC-CAGEFREE I (Drug-Coated Balloon Angioplasty With Rescue Stenting Versus Intended Stenting for the Treatment of Patients With de Novo Coronary Artery Lesions)34 não estabeleceu a não inferioridade geral dos BRP; no entanto, os desfechos no subgrupo com DACPV (diâmetro do dispositivo < 3,0 mm) foram comparáveis (p de interação = 0,02).

Embora as diretrizes atuais recomendem SF em vez de BF para reestenose intra-stent,35 o uso de BF para lesões de novo em pequenos vasos tem ganhado espaço na prática clínica, especialmente entre pacientes com alto risco de sangramento. Embora ainda não esteja incorporada nas principais diretrizes, essa abordagem é apoiada por diversos consensos de especialistas.8-10 Uma vantagem importante do BF é a possibilidade de TAD mais curta, com duração de apenas 30 dias, reduzindo o risco de sangramento36 sem aumento na incidência de ECAM.37 Além disso, a ausência de implante permanente pode diminuir a ocorrência de trombose aguda e subaguda. Ainda assim, são necessários mais dados para confirmar a segurança e eficácia em longo prazo.

Os achados referentes ao risco de sangramento permanecem inconsistentes. Jeger et al.28 relataram um aumento de 2 vezes no risco de sangramento com o uso de SF em 1 ano, enquanto Cortese et al.21 não observaram diferenças significativas entre os dispositivos. No estudo DEBUT, que investigou pacientes com alto risco de sangramento tratados com apenas 1 mês de TAD, os BF foram associados a menores taxas de morte CV e IAM, embora as taxas de sangramento tenham sido semelhantes aos 9 meses.38 Importante destacar que os desfechos de sangramento foram reportados de forma inconsistente entre os estudos incluídos nesta metanálise, o que impossibilitou a realização de análise agrupada.

A reestenose continua sendo uma preocupação com o uso de BF. Uma análise com ajuste por escore de propensão do estudo SCAAR (Swedish Coronary Angiography and Angioplasty Registry) identificou maiores taxas de reestenose com os BF; no entanto, não foram observadas diferenças em desfechos duros, como trombose da lesão-alvo, IAM ou óbito.30 De forma semelhante, Latib et al.22 relataram desfechos comparáveis em um ECR com follow-up de 2 anos. Devido à inconsistência na forma de relato, a reestenose não foi analisada nesta metanálise.

Os BFs também podem ser utilizados como parte de uma estratégia híbrida, especialmente em lesões longas ou difusas. Nessa abordagem, os SF são geralmente implantados em vasos de maior calibre com doença residual após a angioplastia com balão, enquanto os BF são reservados para vasos de menor calibre, mais suscetíveis à reestenose, disfunção vasomotora, neoaterosclerose e maiores desafios em cirurgias de revascularização do miocárdio.1,39

Embora todos os BRP liberem paclitaxel, eles diferem em formulação e características do dispositivo, como o excipiente (p.ex., iopromida [SeQuent® Please, B. Braun] vs. ureia [IN.PACT™ Falcon™, Medtronic]) e o perfil do balão. Excipientes hidrofílicos como a ureia podem facilitar a transferência do fármaco e podem ser vantajosos em lesões curtas e simples.40 Flexibilidade e navegabilidade dos dispositivos também variam, o que pode influenciar no sucesso do procedimento em anatomias complexas.

Esta metanálise apresenta várias limitações. A maioria dos estudos incluídos não realizou follow-up angiográfico, o que restringiu a análise de PTL e reestenose. Como consequência, o estudo de Silverio et al.30 — o maior desta metanálise — foi excluído da análise de RLA por ausência de dados disponíveis. Além disso, 11 dos 12 estudos utilizaram SF de segunda geração, fator que deve ser considerado na extrapolação dos resultados.21 Outra limitação é a ausência de uma definição universalmente aceita para DACPV, uma vez que os critérios de diâmetro variaram entre os estudos. Por fim, o número limitado de ECRs exigiu a inclusão de estudos de coorte não randomizados. Embora os ECRs apresentem maior validade interna, os dados observacionais fornecem informações valiosas sobre desfechos em longo prazo.

 Conclusão

Esta revisão sistemática e metanálise, que incluiu 12 estudos, não identificou diferença estatisticamente significativa entre os BRP e os SF no tratamento da DACPV. Esses achados sustentam o potencial dos BF como alternativa segura e eficaz aos stents no manejo da DACPV. No entanto, são necessários novos ECRs com follow-ups mais prolongados para confirmar esses resultados e orientar sua adoção mais ampla na prática clínica rotineira, especialmente para lesões de novo em pequenos vasos coronarianos.

 *Material suplementar Referências 1. Alfonso F, García-Guimaraes M. Optimal Coronary Interventions in Small Vessels: Is Size All That Matters? JACC Cardiovasc Interv. 2016;9(13):1335-7. doi: 10.1016/j.jcin.2016.05.005. Alfonso F García-Guimaraes M Optimal Coronary Interventions in Small Vessels: Is Size All That Matters? JACC Cardiovasc Interv 2016 9 13 1335 1337 10.1016/j.jcin.2016.05.005 2. Godino C, Furuichi S, Latib A, Morici N, Chieffo A, Romagnoli E, et al. Clinical and Angiographic Follow-Up of Small Vessel Lesions Treated with Paclitaxel-Eluting Stents (from the TRUE Registry). Am J Cardiol. 2008;102(8):1002-8. doi: 10.1016/j.amjcard.2008.05.052. Godino C Furuichi S Latib A Morici N Chieffo A Romagnoli E et al Clinical and Angiographic Follow-Up of Small Vessel Lesions Treated with Paclitaxel-Eluting Stents (from the TRUE Registry) Am J Cardiol 2008 102 8 1002 1008 10.1016/j.amjcard.2008.05.052 3. Augustine M, Arain M, Mustafa MS, Moradi I, Fredericks M, Rahman A, et al. Comparative Efficacy and Safety of Drug-Coated Balloons versus Drug-Eluting Stents in Small Vessel Coronary Artery Disease: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials. Egypt Heart J. 2025;77(1):26. doi:10.1186/s43044-025-00621-7. Augustine M Arain M Mustafa MS Moradi I Fredericks M Rahman A et al Comparative Efficacy and Safety of Drug-Coated Balloons versus Drug-Eluting Stents in Small Vessel Coronary Artery Disease: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials Egypt Heart J 2025 77 1 26 10.1186/s43044-025-00621-7 4. Granada JF, Stenoien M, Buszman PP, Tellez A, Langanki D, Kaluza GL, et al. Mechanisms of Tissue Uptake and Retention of Paclitaxel-Coated Balloons: Impact on Neointimal Proliferation and Healing. Open Heart. 2014;1(1):e000117. doi: 10.1136/openhrt-2014-000117. Granada JF Stenoien M Buszman PP Tellez A Langanki D Kaluza GL et al Mechanisms of Tissue Uptake and Retention of Paclitaxel-Coated Balloons: Impact on Neointimal Proliferation and Healing Open Heart 2014 1 1 e000117 10.1136/openhrt-2014-000117 5. Megaly M, Buda K, Saad M, Tawadros M, Elbadawi A, Basir M, et al. Outcomes with Drug-Coated Balloons vs. Drug-Eluting Stents in Small-Vessel Coronary Artery Disease. Cardiovasc Revasc Med. 2022;35:76-82. doi: 10.1016/j.carrev.2021.03.008. Megaly M Buda K Saad M Tawadros M Elbadawi A Basir M et al Outcomes with Drug-Coated Balloons vs. Drug-Eluting Stents in Small-Vessel Coronary Artery Disease Cardiovasc Revasc Med 2022 35 76 82 10.1016/j.carrev.2021.03.008 6. Sedhom R, Hamed M, Elbadawi A, Mohsen A, Swamy P, Athar A, et al. Outcomes with Limus- vs Paclitaxel-Coated Balloons for Percutaneous Coronary Intervention: Meta-Analysis of Randomized Controlled Trials. JACC Cardiovasc Interv. 2024;17(13):1533-43. doi: 10.1016/j.jcin.2024.04.042. Sedhom R Hamed M Elbadawi A Mohsen A Swamy P Athar A et al Outcomes with Limus- vs Paclitaxel-Coated Balloons for Percutaneous Coronary Intervention: Meta-Analysis of Randomized Controlled Trials JACC Cardiovasc Interv 2024 17 13 1533 1543 10.1016/j.jcin.2024.04.042 7. Ninomiya K, Serruys PW, Colombo A, Reimers B, Basavarajaiah S, Sharif F, et al. A Prospective Randomized Trial Comparing Sirolimus-Coated Balloon with Paclitaxel-Coated Balloon in De Novo Small Vessels. JACC Cardiovasc Interv. 2023;16(23):2884-96. doi: 10.1016/j.jcin.2023.09.026. Ninomiya K Serruys PW Colombo A Reimers B Basavarajaiah S Sharif F et al A Prospective Randomized Trial Comparing Sirolimus-Coated Balloon with Paclitaxel-Coated Balloon in De Novo Small Vessels JACC Cardiovasc Interv 2023 16 23 2884 2896 10.1016/j.jcin.2023.09.026 8. Fezzi S, Scheller B, Cortese B, Alfonso F, Jeger R, Colombo A, et al. Definitions and Standardized Endpoints for the Use of Drug-Coated Balloon in Coronary Artery Disease: Consensus Document of the Drug Coated Balloon Academic Research Consortium. EuroIntervention. 2025:EIJ-E-25-00021. doi: 10.4244/EIJ-E-25-00021. Fezzi S Scheller B Cortese B Alfonso F Jeger R Colombo A et al Definitions and Standardized Endpoints for the Use of Drug-Coated Balloon in Coronary Artery Disease: Consensus Document of the Drug Coated Balloon Academic Research Consortium EuroIntervention 2025 EIJ-E-25-00021 10.4244/EIJ-E-25-00021 9. Muramatsu T, Kozuma K, Tanabe K, Morino Y, Ako J, Nakamura S, et al. Clinical Expert Consensus Document on Drug-Coated Balloon for Coronary Artery Disease from the Japanese Association of Cardiovascular Intervention and Therapeutics. Cardiovasc Interv Ther. 2023;38(2):166-76. doi: 10.1007/s12928-023-00921-2. Muramatsu T Kozuma K Tanabe K Morino Y Ako J Nakamura S et al Clinical Expert Consensus Document on Drug-Coated Balloon for Coronary Artery Disease from the Japanese Association of Cardiovascular Intervention and Therapeutics Cardiovasc Interv Ther 2023 38 2 166 176 10.1007/s12928-023-00921-2 10. Jeger RV, Eccleshall S, Wan Ahmad WA, Ge J, Poerner TC, Shin ES, et al. Drug-Coated Balloons for Coronary Artery Disease: Third Report of the International DCB Consensus Group. JACC Cardiovasc Interv. 2020;13(12):1391-402. doi: 10.1016/j.jcin.2020.02.043. Jeger RV Eccleshall S Wan Ahmad WA Ge J Poerner TC Shin ES et al Drug-Coated Balloons for Coronary Artery Disease: Third Report of the International DCB Consensus Group JACC Cardiovasc Interv 2020 13 12 1391 1402 10.1016/j.jcin.2020.02.043 11. Iijima R, Kougame N, Hara H, Moroi M, Nakamura M. Clinical Outcomes of Drug-Coated Balloons in Coronary Artery Disease Unsuitable for Drug-Eluting Stent Implantation. Circ J. 2018;82(8):2025-31. doi: 10.1253/circj.CJ-18-0121. Iijima R Kougame N Hara H Moroi M Nakamura M Clinical Outcomes of Drug-Coated Balloons in Coronary Artery Disease Unsuitable for Drug-Eluting Stent Implantation Circ J 2018 82 8 2025 2031 10.1253/circj.CJ-18-0121 12. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews. BMJ. 2021;372:n71. doi: 10.1136/bmj.n71. Page MJ McKenzie JE Bossuyt PM Boutron I Hoffmann TC Mulrow CD et al The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews BMJ 2021 372 n71 10.1136/bmj.n71 13. Cumpston M, Li T, Page MJ, Chandler J, Welch VA, Higgins JP, et al. Updated Guidance for Trusted Systematic Reviews: A New Edition of the Cochrane Handbook for Systematic Reviews of Interventions. Cochrane Database Syst Rev. 2019;10(10):ED000142. doi: 10.1002/14651858.ED000142. Cumpston M Li T Page MJ Chandler J Welch VA Higgins JP et al Updated Guidance for Trusted Systematic Reviews: A New Edition of the Cochrane Handbook for Systematic Reviews of Interventions Cochrane Database Syst Rev 2019 10 10 ED000142 10.1002/14651858.ED000142 14. Wells GA, Shea B, O'Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle -Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-Analyses [Internet]. Ottawa: Ottawa Hospital Research Institute; 2000 [cited 2025 Aug 31]. Available from: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Wells GA Shea B O'Connell D Peterson J Welch V Losos M et al The Newcastle -Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-Analyses Internet Ottawa Ottawa Hospital Research Institute 2000 cited 2025 Aug 31 http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp 15. Sterne JAC, Savovic J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: A Revised Tool for Assessing Risk of Bias in Randomised Trials. BMJ. 2019;366:l4898. doi: 10.1136/bmj.l4898. Sterne JAC Savovic J Page MJ Elbers RG Blencowe NS Boutron I et al RoB 2: A Revised Tool for Assessing Risk of Bias in Randomised Trials BMJ 2019 366 l4898 10.1136/bmj.l4898 16. GRADEpro GDT. Cochrane GRADEing [Internet]. London: Cochrane Methods; 2025 [cited 2025 Aug 31]. Available from: https://methods.cochrane.org/gradeing/gradepro-gdt. GRADEpro GDT Cochrane GRADEing Internet London Cochrane Methods 2025 cited 2025 Aug 31 https://methods.cochrane.org/gradeing/gradepro-gdt 17. Deeks JJ, Higgins JPT, Altman DG. Chapter 10: Analysing Data and Undertaking Meta-Analyses. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editors. Cochrane Handbook for Systematic Reviews of Interventions. Version 6.4. London: Cochrane; 2023 [cited 2025 Aug 31]. Available from: https://training.cochrane.org/handbook/current/chapter-10. Deeks JJ Higgins JPT Altman DG Chapter 10: Analysing Data and Undertaking Meta-Analyses Higgins JPT Thomas J Chandler J Cumpston M Li T Page MJ Welch VA editors Cochrane Handbook for Systematic Reviews of Interventions Version 6.4 London Cochrane 2023 cited 2025 Aug 31 https://training.cochrane.org/handbook/current/chapter-10 18. Borenstein M, Higgins JP, Hedges LV, Rothstein HR. Basics of Meta-Analysis: I2 is Not an Absolute Measure of Heterogeneity. Res Synth Methods. 2017;8(1):5-18. doi: 10.1002/jrsm.1230. Borenstein M Higgins JP Hedges LV Rothstein HR Basics of Meta-Analysis: I2 is Not an Absolute Measure of Heterogeneity Res Synth Methods 2017 8 1 5 18 10.1002/jrsm.1230 19. IntHout J, Ioannidis JP, Rovers MM, Goeman JJ. Plea for Routinely Presenting Prediction Intervals in Meta-Analysis. BMJ Open. 2016;6(7):e010247. doi: 10.1136/bmjopen-2015-010247. IntHout J Ioannidis JP Rovers MM Goeman JJ Plea for Routinely Presenting Prediction Intervals in Meta-Analysis BMJ Open 2016 6 7 e010247 10.1136/bmjopen-2015-010247 20. R Core Team. R: A Language and Environment for Statistical Computing [Internet]. Vienna: R Foundation for Statistical Computing; 2021 [cited 2025 Aug 31]. Available from: https://www.R-project.org/. R Core Team R: A Language and Environment for Statistical Computing Internet Vienna R Foundation for Statistical Computing 2021 cited 2025 Aug 31 https://www.R-project.org/ 21. Cortese B, Micheli A, Picchi A, Coppolaro A, Bandinelli L, Severi S, et al. Paclitaxel-Coated Balloon versus Drug-Eluting Stent during PCI of Small Coronary Vessels, a Prospective Randomised Clinical Trial. The PICCOLETO Study. Heart. 2010;96(16):1291-6. doi: 10.1136/hrt.2010.195057. Cortese B Micheli A Picchi A Coppolaro A Bandinelli L Severi S et al Paclitaxel-Coated Balloon versus Drug-Eluting Stent during PCI of Small Coronary Vessels, a Prospective Randomised Clinical Trial. The PICCOLETO Study Heart 2010 96 16 1291 1296 10.1136/hrt.2010.195057 22. Latib A, Colombo A, Castriota F, Micari A, Cremonesi A, De Felice F, et al. A Randomized Multicenter Study Comparing a Paclitaxel Drug-Eluting Balloon with a Paclitaxel-Eluting Stent in Small Coronary Vessels: The BELLO (Balloon Elution and Late Loss Optimization) Study. J Am Coll Cardiol. 2012;60(24):2473-80. doi: 10.1016/j.jacc.2012.09.020. Latib A Colombo A Castriota F Micari A Cremonesi A De Felice F et al A Randomized Multicenter Study Comparing a Paclitaxel Drug-Eluting Balloon with a Paclitaxel-Eluting Stent in Small Coronary Vessels: The BELLO (Balloon Elution and Late Loss Optimization) Study J Am Coll Cardiol 2012 60 24 2473 2480 10.1016/j.jacc.2012.09.020 23. Giannini F, Latib A, Ancona MB, Costopoulos C, Ruparelia N, Menozzi A, et al. A Propensity Score Matched Comparative Study between Paclitaxel-Coated Balloon and Everolimus-Eluting Stents for the Treatment of Small Coronary Vessels. Catheter Cardiovasc Interv. 2017;90(3):380-6. doi: 10.1002/ccd.26929. Giannini F Latib A Ancona MB Costopoulos C Ruparelia N Menozzi A et al A Propensity Score Matched Comparative Study between Paclitaxel-Coated Balloon and Everolimus-Eluting Stents for the Treatment of Small Coronary Vessels Catheter Cardiovasc Interv 2017 90 3 380 386 10.1002/ccd.26929 24. Sim HW, Ananthakrishna R, Chan SP, Low AF, Lee CH, Chan MY, et al. Treatment of Very Small De Novo Coronary Artery Disease With 2.0 mm Drug-Coated Balloons Showed 1-Year Clinical Outcome Comparable With 2.0 mm Drug-Eluting Stents. J Invasive Cardiol. 2018;30(7):256-61. Sim HW Ananthakrishna R Chan SP Low AF Lee CH Chan MY et al Treatment of Very Small De Novo Coronary Artery Disease With 2.0 mm Drug-Coated Balloons Showed 1-Year Clinical Outcome Comparable With 2.0 mm Drug-Eluting Stents J Invasive Cardiol 2018 30 7 256 261 25. Kawai T, Watanabe T, Yamada T, Morita T, Furukawa Y, Tamaki S, et al. Coronary Vasomotion after Treatment with Drug-Coated Balloons or Drug-Eluting Stents: A Prospective, Open-Label, Single-Centre Randomised Trial. EuroIntervention. 2022;18(2):e140-e148. doi: 10.4244/EIJ-D-21-00636. Kawai T Watanabe T Yamada T Morita T Furukawa Y Tamaki S et al Coronary Vasomotion after Treatment with Drug-Coated Balloons or Drug-Eluting Stents: A Prospective, Open-Label, Single-Centre Randomised Trial EuroIntervention 2022 18 2 e140 e148 10.4244/EIJ-D-21-00636 26. Tsai CH, Yeh CF, Meng SW, Hung CS, Lin MS, Huang CC, et al. Comparison between Drug-Coated Balloons and Drug-Eluting Stents in Very Small Coronary Artery Interventions. Sci Rep. 2022;12(1):10679. doi: 10.1038/s41598-022-14047-7. Tsai CH Yeh CF Meng SW Hung CS Lin MS Huang CC et al Comparison between Drug-Coated Balloons and Drug-Eluting Stents in Very Small Coronary Artery Interventions Sci Rep 2022 12 1 10679 10.1038/s41598-022-14047-7 27. Sinaga DA, Ho HH, Watson TJ, Sim A, Nyein TT, Jafary FH, et al. Drug-Coated Balloons: A Safe and Effective Alternative to Drug-Eluting Stents in Small Vessel Coronary Artery Disease. J Interv Cardiol. 2016;29(5):454-60. doi: 10.1111/joic.12333. Sinaga DA Ho HH Watson TJ Sim A Nyein TT Jafary FH et al Drug-Coated Balloons: A Safe and Effective Alternative to Drug-Eluting Stents in Small Vessel Coronary Artery Disease J Interv Cardiol 2016 29 5 454 460 10.1111/joic.12333 28. Jeger RV, Farah A, Ohlow MA, Mangner N, Möbius-Winkler S, Leibundgut G, et al. Drug-Coated Balloons for Small Coronary Artery Disease (BASKET-SMALL 2): An Open-Label Randomised Non-Inferiority Trial. Lancet. 2018;392(10150):849-56. doi: 10.1016/S0140-6736(18)31719-7. Jeger RV Farah A Ohlow MA Mangner N Möbius-Winkler S Leibundgut G et al Drug-Coated Balloons for Small Coronary Artery Disease (BASKET-SMALL 2): An Open-Label Randomised Non-Inferiority Trial Lancet 2018 392 10150 849 856 10.1016/S0140-6736(18)31719-7 29. Tang Y, Qiao S, Su X, Chen Y, Jin Z, Chen H, et al. Drug-Coated Balloon versus Drug-Eluting Stent for Small-Vessel Disease: The RESTORE SVD China Randomized Trial. JACC Cardiovasc Interv. 2018;11(23):2381-92. doi: 10.1016/j.jcin.2018.09.009. Tang Y Qiao S Su X Chen Y Jin Z Chen H et al Drug-Coated Balloon versus Drug-Eluting Stent for Small-Vessel Disease: The RESTORE SVD China Randomized Trial JACC Cardiovasc Interv 2018 11 23 2381 2392 10.1016/j.jcin.2018.09.009 30. Silverio A, Buccheri S, Venetsanos D, Alfredsson J, Lagerqvist B, Persson J, et al. Percutaneous Treatment and Outcomes of Small Coronary Vessels: A SCAAR Report. JACC Cardiovasc Interv. 2020;13(7):793-804. doi: 10.1016/j.jcin.2019.10.062. Silverio A Buccheri S Venetsanos D Alfredsson J Lagerqvist B Persson J et al Percutaneous Treatment and Outcomes of Small Coronary Vessels: A SCAAR Report JACC Cardiovasc Interv 2020 13 7 793 804 10.1016/j.jcin.2019.10.062 31. Cortese B, Di Palma G, Guimaraes MG, Piraino D, Orrego PS, Buccheri D, et al. Drug-Coated Balloon versus Drug-Eluting Stent for Small Coronary Vessel Disease: PICCOLETO II Randomized Clinical Trial. JACC Cardiovasc Interv. 2020;13(24):2840-9. doi: 10.1016/j.jcin.2020.08.035. Cortese B Di Palma G Guimaraes MG Piraino D Orrego PS Buccheri D et al Drug-Coated Balloon versus Drug-Eluting Stent for Small Coronary Vessel Disease: PICCOLETO II Randomized Clinical Trial JACC Cardiovasc Interv 2020 13 24 2840 2849 10.1016/j.jcin.2020.08.035 32. Liu S, Zhou Y, Shen Z, Chen H, Qiu C, Fu G, et al. Comparison of Drug-Coated Balloon and Drug-Eluting Stent for the Treatment of Small Vessel Disease (from the Dissolve SVD Randomized Trial). Am J Cardiol. 2024;211:29-39. doi: 10.1016/j.amjcard.2023.05.057. Liu S Zhou Y Shen Z Chen H Qiu C Fu G et al Comparison of Drug-Coated Balloon and Drug-Eluting Stent for the Treatment of Small Vessel Disease (from the Dissolve SVD Randomized Trial) Am J Cardiol 2024 211 29 39 10.1016/j.amjcard.2023.05.057 33. Cortese B, Testa G, Rivero F, Erriquez A, Alfonso F. Long-Term Outcome of Drug-Coated Balloon vs Drug-Eluting Stent for Small Coronary Vessels: PICCOLETO-II 3-Year Follow-Up. JACC Cardiovasc Interv. 2023;16(9):1054-61. doi: 10.1016/j.jcin.2023.02.011. Cortese B Testa G Rivero F Erriquez A Alfonso F Long-Term Outcome of Drug-Coated Balloon vs Drug-Eluting Stent for Small Coronary Vessels: PICCOLETO-II 3-Year Follow-Up JACC Cardiovasc Interv 2023 16 9 1054 1061 10.1016/j.jcin.2023.02.011 34. Gao C, He X, Ouyang F, Zhang Z, Shen G, Wu M, et al. Drug-Coated Balloon Angioplasty with Rescue Stenting versus Intended Stenting for the Treatment of Patients with de Novo Coronary Artery Lesions (REC-CAGEFREE I): An Open-Label, Randomised, Non-Inferiority Trial. Lancet. 2024;404(10457):1040-50. doi: 10.1016/S0140-6736(24)01594-0. Gao C He X Ouyang F Zhang Z Shen G Wu M et al Drug-Coated Balloon Angioplasty with Rescue Stenting versus Intended Stenting for the Treatment of Patients with de Novo Coronary Artery Lesions (REC-CAGEFREE I): An Open-Label, Randomised, Non-Inferiority Trial Lancet 2024 404 10457 1040 1050 10.1016/S0140-6736(24)01594-0 35. Vrints C, Andreotti F, Koskinas KC, Rossello X, Adamo M, Ainslie J, et al. 2024 ESC Guidelines for the Management of Chronic Coronary Syndromes. Eur Heart J. 2024;45(36):3415-537. doi: 10.1093/eurheartj/ehae177. Vrints C Andreotti F Koskinas KC Rossello X Adamo M Ainslie J et al 2024 ESC Guidelines for the Management of Chronic Coronary Syndromes Eur Heart J 2024 45 36 3415 3537 10.1093/eurheartj/ehae177 36. Johnston SC, Rootenberg JD, Katrak S, Smith WS, Elkins JS. Effect of a US National Institutes of Health Programme of Clinical Trials on Public Health and Costs. Lancet. 2006;367(9519):1319-27. doi: 10.1016/S0140-6736(06)68578-4. Johnston SC Rootenberg JD Katrak S Smith WS Elkins JS Effect of a US National Institutes of Health Programme of Clinical Trials on Public Health and Costs Lancet 2006 367 9519 1319 1327 10.1016/S0140-6736(06)68578-4 37. Corballis N, Bhalraam U, Merinopoulos I, Gunawardena T, Tsampasian V, Wickramarachchi U, et al. One-Month Duration Compared with Twelve-Month Duration of Dual Antiplatelet Therapy in Elective Angioplasty for Coronary Artery Disease: Bleeding and Ischaemic Outcomes. J Clin Med. 2024;13(15):4521. doi: 10.3390/jcm13154521. Corballis N Bhalraam U Merinopoulos I Gunawardena T Tsampasian V Wickramarachchi U et al One-Month Duration Compared with Twelve-Month Duration of Dual Antiplatelet Therapy in Elective Angioplasty for Coronary Artery Disease: Bleeding and Ischaemic Outcomes J Clin Med 2024 13 15 4521 10.3390/jcm13154521 38. Rissanen TT, Uskela S, Eränen J, Mäntylä P, Olli A, Romppanen H, et al. Drug-Coated Balloon for Treatment of de-Novo Coronary Artery Lesions in Patients with High Bleeding Risk (DEBUT): A Single-Blind, Randomised, Non-Inferiority Trial. Lancet. 2019;394(10194):230-239. doi: 10.1016/S0140-6736(19)31126-2. Rissanen TT Uskela S Eränen J Mäntylä P Olli A Romppanen H et al Drug-Coated Balloon for Treatment of de-Novo Coronary Artery Lesions in Patients with High Bleeding Risk (DEBUT): A Single-Blind, Randomised, Non-Inferiority Trial Lancet 2019 394 10194 230 239 10.1016/S0140-6736(19)31126-2 39. Lawton JS, Tamis-Holland JE, Bangalore S, Bates ER, Beckie TM, Bischoff JM, et al. 2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022;145(3):e18-e114. doi: 10.1161/CIR.0000000000001038. Lawton JS Tamis-Holland JE Bangalore S Bates ER Beckie TM Bischoff JM et al 2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines Circulation 2022 145 3 e18 e114 10.1161/CIR.0000000000001038 40. Tepe G, Laird J, Schneider P, Brodmann M, Krishnan P, Micari A, et al. Drug-Coated Balloon versus Standard Percutaneous Transluminal Angioplasty for the Treatment of Superficial Femoral and Popliteal Peripheral Artery Disease: 12-Month Results from the IN.PACT SFA Randomized Trial. Circulation. 2015;131(5):495-502. doi: 10.1161/CIRCULATIONAHA.114.011004. Tepe G Laird J Schneider P Brodmann M Krishnan P Micari A et al Drug-Coated Balloon versus Standard Percutaneous Transluminal Angioplasty for the Treatment of Superficial Femoral and Popliteal Peripheral Artery Disease: 12-Month Results from the IN.PACT SFA Randomized Trial Circulation 2015 131 5 495 502 10.1161/CIRCULATIONAHA.114.011004

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

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

Os autores não utilizaram ferramentas de inteligência artificial no desenvolvimento deste trabalho.

Os conteúdos subjacentes ao texto da pesquisa estão contidos no manuscrito.

Para informação adicional, por favor clique aqui.

O presente estudo não teve fontes de financiamento externas.

 10.36660/abc.20250069i Original Article Paclitaxel-Coated Balloons versus Drug-Eluting Stents in Small Vessel Coronary Artery Disease: A Systematic Review and Meta-Analysis 0000-0002-7329-5060 Gobbo Marília Oberto da Silva Conception and design of the research Acquisition of data Analysis and interpretation of the data Writing of the manuscript 1 Sudo Renan Yuji Ura Analysis and interpretation of the data Statistical analysis Writing of the manuscript 2 Franco Ancy Jenil Acquisition of data Analysis and interpretation of the data Writing of the manuscript Critical revision of the manuscript for content 3 Pereira Mable Acquisition of data Analysis and interpretation of the data Writing of the manuscript 4 Milbradt Tanize Louize Conception and design of the research Acquisition of data Analysis and interpretation of the data Writing of the manuscript 5 Bakir Zeynep Eylul Acquisition of data Analysis and interpretation of the data Writing of the manuscript 6 Pires Iago Zang Acquisition of data Analysis and interpretation of the data Writing of the manuscript 1 Akinfenwa Stephen Writing of the manuscript Critical revision of the manuscript for content 7 0000-0002-3668-9976 Agostini Gustavo Luís Analysis and interpretation of the data Writing of the manuscript Critical revision of the manuscript for content 8 0000-0002-4207-5364 Pellegrini Denise Analysis and interpretation of the data Writing of the manuscript Critical revision of the manuscript for content 9 0000-0002-7895-8281 Caramori Paulo R. A. Critical revision of the manuscript for content 9 Brazil Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS – Brazil Brazil Universidade Federal da Grande Dourados, Dourados, MS – Brazil USA McLaren Bay Region, Internal Medicine Department, Bay City, Michigan – USA Guyana Lincoln American University School of Medicine, Georgetown – Guyana Brazil Universidade Federal de Santa Maria, Santa Maria, RS – Brazil Italy University of Rome La Sapienza, Rome, Lazio – Italy USA University of Connecticut, Storrs – USA Brazil Tacchini Hospital, Bento Gonçalves, RS – Brazil Brazil Hospital São Lucas da PUCRS, Porto Alegre, RS – Brazil Paulo R. A. Caramori Hospital São Lucas da PUCRS – Av. Ipiranga 6690 – Sala 300. Postal Code 90610-000, Porto Alegre, RS – Brazil E-mail: caramori@cardiarte.com.br

No potential conflict of interest relevant to this article was reported.

Henrique Ribeiro

 Abstract Background

Drug-eluting stents (DES) remain the standard of care for percutaneous coronary intervention in small vessel coronary artery disease (SVD). Paclitaxel-coated balloons (PCB) have emerged as an alternative, with recent trials suggesting favorable short- and mid-term outcomes, although most were limited by small sample sizes.

 Objectives

To compare angiographic and clinical outcomes between DES and PCB in patients with SVD.

 Methods

Searches were conducted in PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov for studies comparing PCB and DES in SVD, defined as a reference vessel diameter < 3.0 mm. A random-effects meta-analysis was performed, and results were reported as mean differences (MD) or risk ratios (RR). Statistical significance was set at p < 0.05. Heterogeneity was assessed using the chi-square, Tau, and Tau2 tests. The review protocol was registered in PROSPERO (CRD42024506502).

 Results

A total of 12 studies comprising 17,441 patients (mean age of 58-73 years) were included, with clinical follow-up of 8 to 36 months. All studies evaluated PCB. No significant differences were found between PCB and DES in target lesion revascularization (RR, 1.24; 95% CI, 0.82-1.85; p = 0.30), late lumen loss (MD, –0.09 mm; 95% CI, –0.41 to 0.23; p = 0.57), major adverse cardiovascular events (RR, 1.01; 95% CI, 0.76-1.33; p = 0.95), all-cause mortality (RR, 0.81; 95% CI, 0.50-1.31; p = 0.39), cardiovascular mortality (RR, 1.74; 95% CI, 0.78-3.89; p = 0.17), and myocardial infarction (RR, 0.76; 95% CI, 0.46-1.27; p = 0.30).

 Conclusions

PCB angioplasty demonstrated clinical and angiographic outcomes comparable to DES in SVD, supporting its role as a safe, effective alternative in selected patients.

Balões Revestidos com Paclitaxel versus Stents Farmacológicos na Doença Arterial Coronariana de Pequenos Vasos: Revisão Sistemática e Metanálise BRP: balão revestido com paclitaxel; DACPV: doença arterial coronariana de pequenos vasos; ECAM: eventos cardiovasculares adversos maiores; IAM: infarto agudo do miocárdio; intervalo de confiança de 95%; RLA: revascularização da lesão-alvo; SF: stent farmacológico.

Keywords: Drug-Eluting Stents Coronary Artery Disease Percutaneous Coronary Intervention Introduction

Small vessel coronary artery disease (SVD) is common in patients undergoing percutaneous coronary intervention (PCI), representing up to 50% of all procedures performed annually.1 Treating SVD with drug-eluting stents (DES) presents distinct challenges, including an increased risk of dissection, vessel rupture, and restenosis as well as the requirement for sustained dual antiplatelet therapy (DAPT) after stent implantation.2

Although DES have shown superiority over plain balloon angioplasty, drug-coated balloons (DCB) have emerged as a promising alternative in specific anatomical settings, including SVD.3 DCBs are balloon catheters coated with antiproliferative agents — most commonly paclitaxel, sirolimus, or other limus analogs — that are delivered to the vessel wall during balloon inflation.4 The balloon is typically inflated for 30-60 seconds. This strategy avoids the implantation of permanent foreign material, which may reduce late inflammatory reactions and lower the risk of restenosis and thrombosis. The lack of a metallic scaffold and durable polymer helps preserve vascular anatomy and vasomotor function, thereby minimizing hemodynamic disturbances and potentially reducing the need for sustained DAPT.5

Paclitaxel is cytotoxic, but it achieves cytotoxic concentrations in the vessel wall only during the first hours after DCB application. Thereafter, its activity resembles that of sirolimus. Because of its high lipophilicity, paclitaxel demonstrates greater retention in the vessel wall, resulting in more sustained inhibition of neointimal proliferation compared with limus-based drugs. This may provide a long-term advantage for paclitaxel-coated balloons (PCB) over sirolimus-coated devices.6,7

Despite expert consensus supporting DCB angioplasty as a feasible alternative to DES in SVD, evidence from randomized controlled trials (RCTs) remains limited, primarily because of small sample sizes.8-11 Accordingly, we performed a systematic review and meta-analysis to synthesize available data comparing clinical outcomes of these 2 treatment strategies.

 Methods Eligibility criteria

Studies were eligible for inclusion if they met the following criteria: RCTs or nonrandomized cohort studies; PCI strategies involving either DCB or DES; and enrollment of patients with SVD (reference vessel diameter < 3.0 mm). Studies were included only if they reported at least 1 relevant clinical outcome.

Studies with inappropriate comparators, reference vessel diameter ≥ 3mm, follow-up shorter than 6 months, unavailable full text, or publications in languages other than English were excluded.

 Search strategy and data extraction

This systematic review and meta-analysis followed Cochrane Collaboration recommendations and was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) (Table S1).12,13 The review protocol was prospectively registered in the PROSPERO database on January 25, 2024, under the registry code CRD42024506502.

Searches were conducted by 2 review authors in PubMed, Embase, and Cochrane Library from inception to January 2024, using the terms drug-coated balloon, drug-eluting stent, and coronary small vessel. The complete search strategy is provided in the Supplementary Material. Reference lists were also screened for relevant studies. ClinicalTrials.gov was searched to identify additional relevant trials not captured by the primary search.

Study characteristics, baseline data, and clinical outcomes were independently extracted by 4 review authors according to predefined criteria and assessments of quality. Disagreements were resolved through discussion with 2 additional review authors and, when necessary, by consultation with the senior review authors.

 Outcomes and subanalyses

The primary outcome was the incidence of clinically driven target lesion revascularization (TLR) at the longest available follow-up. The main secondary angiographic outcome was late lumen loss (LLL). Additional outcomes of interest included major adverse cardiovascular events (MACE), all-cause mortality, cardiovascular (CV) mortality, and myocardial infarction (MI). Detailed outcome data for each study are presented in the Supplementary Material (Table S2).

 Assessment of quality

Nonrandomized cohort studies were evaluated using the Newcastle-Ottawa Scale (NOS).14 This tool assigns up to 9 stars based on 3 domains: selection of participants, comparability of study groups, and ascertainment of outcomes (Table S3). RCTs were assessed using the Cochrane Risk of Bias Tool 2.0 (RoB 2), which classifies studies as having “low risk of bias,” “some concerns,” or “high risk of bias” across 5 domains: the randomization process, deviations from intended interventions, missing outcome data, measurement of the outcome, and selection of the reported result (Figure S4).15

Certainty of evidence was assessed by 2 independent review authors (R.S. and M.G.) using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation), with levels ranging from high to very low (Table S5).16 Publication bias was explored using funnel-plot analysis of point estimates weighted by study size and Egger’s regression test.

 Statistical analysis

Data were synthesized using a random-effects meta-analysis with a restricted maximum likelihood estimator. This model was chosen to account for potential clinical, methodological, and statistical heterogeneity, as it recognizes that the true effect of the intervention may vary across studies.17,18 Binary outcomes were expressed as risk ratios (RR), and continuous outcomes as mean differences (MD). Subgroup analyses compared outcomes between randomized trials and observational studies, accounting for potential qualitative and quantitative interactions. Statistical significance was set at a 95% CI and a p-value < 0.05. Heterogeneity was assessed with chi-square, Tau, and Tau2 tests. To avoid misleading interpretation from a fixed threshold for I2, heterogeneity was further evaluated in relation to the prediction interval (PI).18,19 All statistical analyses were performed in R software version 4.4.1 (R Foundation for Statistical Computing).20

 Results Search strategy and baseline characteristics of the included studies

The initial search identified 566 records. After the removal of 236 duplicates, 312 articles were excluded based on title and abstract review (Figure 1). A total of 18 articles underwent full-text evaluation. Of these, 2 were excluded due to unavailability of the full text, 1 for using an inappropriate comparator, and 3 for enrolling patients with a reference vessel diameter ≥ 3 mm. A total of 12 studies comprising 17,441 patients with SVD were included.21-32 They were published between 2010 and 2024, with a mean follow-up of 8-36 months. All DCBs were paclitaxel-coated. Commercial names of PCBs and DES used in the individual studies are listed in the Supplementary Material (Table S6).

– PRISMA flow diagram of study identification, screening, and inclusion. PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Characteristics of the included studies and interventions are summarized in Tables 1 and 2. At baseline, the population was predominantly male, with a mean age of 64 years and a high prevalence of diabetes and hypertension. The mean reference vessel diameter was 2.19 mm. The left anterior descending artery was the most common site of target lesions. Nearly half of patients presented with multivessel disease. Left ventricular ejection fraction (LVEF) was not reported in half of the studies; in those that provided data, LVEF values were within the range consistent with preserved EF.

– Baseline clinical characteristics of the included studies
Study/ Characteristic Cortese, et al., 201021 Latib, et al., 201222 Sinaga, et al., 201627 Giannini, et al., 201723 Jeger, et al., 201828 Sim, et al., 201824 Tang, et al., 201829 Cortese, et aI., 202031 Silverio, et al., 202030 Tsai, et al., 202226 Kawai, et al., 202225 Liu, et al., 202432
Sample size, n 28/29 90/92 172/163 90/91 382/376 87/200 116/110 118/114 1154/13634 47/59 19/23 129/118
Study design RCT RCT Retrospective Cohort Retrospective Cohort RCT Retrospective Cohort RCT RCT Prospective Cohort Retrospective Cohort RCT RCT
Clinical follow-up, months 9 24 12 12 12 12 12 12 36 12 8 12
Age, years 68/67 65/66 61/61 65/66 67/68 58/61 60/60 64/66 68/69 65 69/73 60/60
Male sex, % 79/76 80/77 77/72 80/78 77/70 81/77 77/77 77/70 70/66 83/81 79/74 73/70
Diabetes, % 46/37 43/38 51/49 43/40 32/34 63/54 39/43 38/35 35/38 49/54 26/34 35/38
Hyperlipidemia, % 60/45 78/79 70/72 79/78 68/69 80/76 52/50 60/55 59/50 85/71 79/82 45/54
Hypertension, % 75/69 80/81 72/69 78/81 84/88 79/68 67/78 65/66 68/64 93/83 89/91 73/75
Current smoker, % NA 16/10 30/44 43/33 21/19 48/29 29/32 19/16 12/16 44/35 52/52 21/21
Previous MI, % 17/20 51/35 28/27 51/58 41/35 56/57 22/25 28/39 31/24 10/11 10/21 25/22
Stable CAD, % 46/44 75/78 22/34 75/81 70/73 NA 31/30 53/56 32/23 87/81 100/100 20/25
Unstable angina, % 53/55 24/21 49/38 24/18 12/11 NA 69/73 15/15 11/10 12/18 0 63/65
NSTEMI, % 0 0 — 0 13/14 35/30 0 19/22 41/43 — 0 0
STEMI, % 0 0 28/27 0 3/1 20/27 0 10/7 14/23 NA 0 0
LVEF, % NA NA NA NA 60/60 NA 60/60 58/58 NA 58/59 67/66 62/61
Multivessel disease, % 60/65 62/60 NA 61/71 82/75 72/78 41/41 72/75 37/49 NA 0/0 0/0.8

Values are presented as means unless otherwise specified. The statistical significance level adopted in the included studies was 5%, when available in the original publications. CAD: coronary artery disease; DCB: drug-coated balloon; DES: drug-eluting stent; LVEF: left ventricular ejection fraction; MI: myocardial infarction; NA: not applicable; NSTEMI: non-ST-segment elevation MI; RCT: randomized controlled trial; STEMI: ST-segment elevation MI.

– Baseline angiographic and procedural characteristics of the included studies
Study/ Characteristic Cortese, et al., 201021 Latib, et al., 201222 Sinaga, et al., 201627 Giannini, et al., 201723 Jeger, et al., 201828 Sim, et al., 201824 Tang, et al., 201829 Cortese, et aI., 202031 Silverio, et al., 202030 Tsai, et al., 202226 Kawai, et al., 202225 Liu, et al., 202432
Sample size, n 28/29 90/92 172/163 90/91 382/376 87/200 116/110 118/114 1154/13634 47/59 19/23 129/118
Angiographic follow-up, months 6 24 12 12 12 12 9 6 36 12 8 9
Left anterior descending coronary artery, % 54/52 11/11 41/41 11/17 34/31 NA 10/10 39/40 49/45 42/44 42/17 22/23
Diagonal coronary artery, % NA 17/8 NA 17/16 NA NA 14/15 NA NA NA NA NA
Left circumflex coronary artery, % 18/10 11/16 32/34 11/13 47/49 NA 59/47 31/37 35/32 36/43 26/61 52/48
Left main coronary artery, % NA NA NA NA NA NA NA NA 0.4/0.5 NA NA NA
Obtuse marginal artery, % NA 27/32 NA 27/18 NA NA 4/6 NA NA NA NA NA
Right coronary artery, % 28/38 8/9 26/23 8/11 20/20 NA 9/10 30/23 15/22 22/13 32/22 26/29
Posterior descending / posterolateral coronary artery, % NA 27/22 NA 27/20 NA NA 20/26 NA NA NA NA NA
Lesion length, mm 12.4/11.3 15.4/14.4 NA NA NA 18.5/20.3 10.5/10.8 13.5/14 NA 19.8/20 11.8/11.3 12.3/11.5
Diameter stenosis, % 86/89 82/83 NA 82/82 NA 88/90 70/71 75/76 NA 87/86 68/60 69/71
Minimum lumen diameter, mm 0.48/0.40 NA NA NA NA 0.20/0.19 0.64/0.65 0.82/0.83 NA 0.29/0.29 0.75/0.80 0.68/0.65
Reference vessel diameter, mm 2.45/2.36 2.41/2.41 2.22/2.44 2.49/2.5 NA 1.88/1.95 2.42/2.42 2.23/2.18 2.23/2.18 2.1/2.1 2.29/2.08 2.2/2.21
Device pressure, ATM 7.7/13.4 9.6/17.2 NA 9.6/17.8 11.1/13.6 NA 9.1/10.7 13.7/11.4 10/18 NA 7.7/13 10.2/10.8
Device diameter, mm 2.48/2.54 2.49/2.49 2.25/2.5 2.49/2.5 2.75/2.57 NA 2.41/2.41 NA 2.5/2.5 2.09/2.18 2.6/2.4 2.44/2.42
Device length, mm 18.6/18.9 25.6/18.5 20.2/22.2 25.6/27.1 23.9/23.1 NA 21/20.4 21.8/18.3 20/18 26/25 19/17 20.5/19.4

Values are presented as absolute numbers (n) or percentages (%). The statistical significance level adopted in the included studies was 5% when available in the original publications. ATM: atmospheres.

 Outcomes

At a mean follow-up of 32.4 months, no statistically significant differences were found between DCB and DES for any of the analyzed outcomes. The primary outcome, TLR, occurred in 6.6% of patients in the DCB group compared with 5.3% in the DES group (RR, 1.24; 95% CI, 0.82-1.85; Figure 2A). The secondary angiographic outcome, LLL, was also similar between groups (MD, –0.09 mm; 95% CI, –0.41 to 0.23), with mean values of 0.17 mm in the DCB group and 0.16 mm in the DES group (Figure 2B). Other angiographic outcomes showed no significant differences and are presented in Supplementary Figures S7A and S7B.

– Comparison of Target Lesion Revascularization and Late Lumen Loss Between Paclitaxel-Coated Balloons and Drug-Eluting Stents in Small Vessel Disease. DCB: drug-coated balloon; DES: drug-eluting stent; LLL: late lumen loss; PCB: paclitaxel-coated balloon; PI: prediction interval; RR: risk ratio; TLR: target lesion revascularization.

Clinical outcomes likewise did not differ significantly between groups. RR for MACE was 1.01 (95% CI, 0.76-1.33; Figure 3A); for all-cause mortality, 0.81 (95% CI, 0.50-1.30; Figure 3B); for CV mortality, 1.74 (95% CI, 0.78-3.89; p = 0.17; I2 = 0%; PI = 0.01-323.77; Figure S8); and for MI, 0.76 (95% CI, 0.46-1.27; Figure 3C). Central Illustration summarizes the key findings of the review.

– Comparison of Major Adverse Cardiovascular Events, All-Cause Mortality, and Myocardial Infarction Between Paclitaxel-Coated Balloons and Drug-Eluting Stents in Small Vessel Disease. MACE: major adverse cardiovascular events; DCB: drug-coated balloon; DES: drug-eluting stent; PCB: paclitaxel-coated balloon; PI: prediction interval; RR: risk ratio.

Subgroup analyses by study design (RCTs vs. nonrandomized cohort studies) yielded consistent results.

 Assessment of quality and certainty of evidence

The risk of bias for RCTs and nonrandomized cohort studies included in this meta-analysis was considered low (Table S4).

Funnel-plot analysis of the MACE outcome, used to assess potential publication bias through visual inspection of asymmetry, suggested a favorable bias toward DCB benefits (Figure 4). However, Egger’s regression test did not reach statistical significance for publication bias. Complete GRADE is provided in the Supplementary Material (Table S5).

– Funnel-plot analysis of major adverse cardiac events outcome.

Discussion

This systematic review and meta-analysis comparing PCB and DES in SVD included 12 studies encompassing 17,441 patients, with follow-up durations ranging from 8 to 36 months (mean 32.4 months). No significant differences were observed in the primary outcome, clinically driven TLR, or in secondary outcomes such as LLL, MACE, all-cause mortality, CV mortality, and MI. These findings support the safety and efficacy of PCB as a viable alternative to DES for the treatment of SVD. The consistency of results across trials, including those using newer-generation DCBs, further strengthens this evidence.

Our pooled analysis highlighted a high prevalence of CV risk factors, with more than half of the patients presenting with hypertension and over one-third with diabetes, reflecting a real-world population undergoing PCI for SVD.

The largest trial included, BASKET-SMALL 2 (Basel Stent Kosten Effektivitäts Trial Drug Eluting Balloons vs Drug Eluting Stents in Small Vessel Interventions),28 enrolled patients with successful lesion pre-dilatation and reported no significant difference in MACE at 12 months between DCB and DES groups (7.3% vs 7.5%; hazard ratio, 0.97; 95% CI, 0.58-1.64; p = 0.92) as well as similar rates of cardiac death, MI, and target vessel revascularization. By contrast, the PICCOLETO II (Drug Eluting Balloon Efficacy for Small Coronary Vessel Disease Treatment) trial31 demonstrated superiority of DCB over DES in terms of in-lesion LLL at 6 months. Long-term follow-up showed similar mortality and MI rates, but higher MACE and acute vessel occlusion in the DES group (20.8% vs 10.8%, p = 0.046; and 4% vs 0%, p = 0.042, respectively).33 The REC-CAGEFREE I (Drug-Coated Balloon Angioplasty With Rescue Stenting Versus Intended Stenting for the Treatment of Patients With de Novo Coronary Artery Lesions) trial34 did not establish overall noninferiority of PCB; however, outcomes in the SVD subgroup (device diameter < 3.0 mm) were comparable (p-value for interaction = 0.02).

Although current guidelines recommend DES over DCB for in-stent restenosis,35 the use of DCB for de novo lesions in small vessels has gained traction in clinical practice, particularly among patients at high bleeding risk. While not yet incorporated into major guidelines, this approach is endorsed by several expert consensus statements.8-10 A key advantage of DCB is the possibility of shorter DAPT, as brief as 30 days, thereby reducing bleeding risk36 without increasing MACE.37 In addition, the lack of a permanent implant may decrease the incidence of acute and subacute thrombosis. Nevertheless, further evidence is required to confirm long-term safety and efficacy.

Findings regarding bleeding risk remain inconsistent. Jeger et al.28 reported a 2-fold increase in bleeding with DES at 1 year, whereas Cortese et al.21 found no significant differences between devices. In the DEBUT trial, which investigated high bleeding risk patients treated with only 1 month of DAPT, DCB was associated with lower CV death and MI rates, although bleeding rates were similar at 9 months.38 Importantly, bleeding outcomes were inconsistently reported across the studies included in this meta-analysis, precluding a pooled analysis.

Restenosis continues to be a concern with DCB. A propensity-adjusted analysis from the SCAAR (Swedish Coronary Angiography and Angioplasty Registry) trial found higher restenosis rates with DCB; however, no differences were seen in hard outcomes such as target lesion thrombosis, MI, or death.30 Similarly, Latib et al.22 reported comparable outcomes in a RCT with 2-year follow-up. Because of inconsistent reporting, restenosis was not analyzed in this meta-analysis.

DCBs may also be used as part of a hybrid strategy, particularly in long or diffuse lesions. In this approach, DES are typically implanted in large vessels with residual disease after balloon angioplasty, whereas DCBs are reserved for small vessels, which are more prone to restenosis, impaired vasomotion, neoatherosclerosis, and future challenges in coronary artery bypass grafting.1,39

Although all PCBs deliver paclitaxel, they differ in formulation and device characteristics, such as the excipient (eg, iopromide [SeQuent® Please, B. Braun] vs. urea [IN.PACT™ Falcon™, Medtronic]) and balloon profile. Hydrophilic excipients like urea may facilitate drug transfer and could be advantageous in short, simple lesions.40 Device flexibility and deliverability also vary, potentially influencing procedural success in complex anatomy.

This meta-analysis has several limitations. Most included studies did not perform angiographic follow-up, restricting the analysis of LLL and restenosis. As a result, the study by Silverio et al.30, the largest in this meta-analysis, was excluded from the TLR outcome due to unavailable data. In addition, 11 of the 12 studies used second-generation DES, a factor that should be considered when extrapolating these results.21 Another limitation is the lack of a universally accepted definition for SVD, as diameter thresholds varied across studies. Finally, the limited number of RCTs required inclusion of nonrandomized cohort studies. While RCTs provide greater internal validity, observational data contribute valuable information on long-term outcomes.

 Conclusion

This systematic review and meta-analysis, encompassing 12 studies, found no statistically significant difference between PCBs and DESs in the treatment of SVD. These findings support the potential role of DCBs as a safe, effective alternative to stents in the treatment of SVD. However, further RCTs with longer follow-ups are warranted to confirm these results and guide their broader adoption in routine clinical practice, particularly for de novo lesions in small coronary vessels.

 Supplemental Materials

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

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

The authors did not use any artificial intelligence tools in the development of this work.

The underlying content of the research text is contained within the manuscript.

For additional information, please click here.

There were no external funding sources for this study.