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Role of sodium-glucose co-transporter-2 inhibitors in cardioprotection in cancer patients treated with anthracyclines : a systematic review and meta-analysis
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Introdução: As antraciclinas são agentes terapêuticos altamente eficazes, mas sua utilização está associada a cardiotoxicidade. Entre os efeitos cardiotóxicos das antraciclinas, destaca-se a prevalente disfunção aguda do ventrículo esquerdo que pode levar à insuficiência cardíaca. Os inibidores do cotransportador sódio-glicose tipo 2 (SGLT2i) demonstraram resultados promissores na prevenção da cardiotoxicidade e no tratamento da insuficiência cardíaca com fração de ejeção reduzida.
Objetivo: O objetivo desta meta-análise é avaliar o impacto do SGLT2i na prevenção da cardiotoxicidade induzida por antraciclinas.
Métodos: Foram incluídos estudos pré-clínicos e clínicos que envolviam terapia com antraciclinas em pacientes sem diagnóstico prévio de insuficiência cardíaca ou tratamento com SGLT2i. Foram examinados um total de 1858 estudos em potencial, dos quais dez foram selecionados para inclusão.
Resultados: Em seis estudos relacionados à função do ventrículo esquerdo, encontramos uma associação significativa a favor do grupo de intervenção (MD 14 (IC 95% = [4,01; 23,99], p = 0,01)). Sete estudos apresentaram resultados significativamente benéficos no grupo de intervenção no que diz respeito à ocorrência de eventos cardíacos adversos e à avaliação histopatológica. Quanto à redução da mortalidade geral, não foi obtido um resultado estatisticamente significativo (HR 0,42 (IC 95% = [0,15; 1,14]), p = 0,09)).
Conclusão: Os grupos tratados com SGLT2i demonstraram valores significativamente favoráveis em relação à função ventricular, redução das alterações histopatológicas (como vacuolização, inflamação e fibrose/necrose), maior estabilidade elétrica cardíaca com menor variação no intervalo QTc, menor taxa de hospitalização devido à insuficiência cardíaca perto da significância na meta-analise e valores mais baixos de NT-proBNP. Quanto à redução da mortalidade geral devido ao uso de SGLT2i nessa população, encontramos resultados divergentes entre os estudos e na meta-análise, o que impossibilita uma interpretação definitiva.
Introduction: Anthracyclines are highly effective therapeutic agents but are associated with cardiotoxicity. Among the cardiotoxic effects of anthracyclines, a prevalent acute left ventricular dysfunction leading to heart failure stands out. Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) have shown promising results in preventing cardiotoxicity and treating heart failure with reduced ejection fraction. Objective: This meta-analisis aims to evaluate the role of SGLT2i in preventing anthracycline-induced cardiotoxicity. Methods: Pre-clinical and clinical studies involving anthracycline therapy, without a prior diagnosis of heart failure or treatment with SGLT2i, were included. A total of 1858 possible studies were researched, of which ten were selected for inclusion. Results: A significant association favoring the intervention group was found in 6 studies related to left ventricular function (MD 14 (95% CI = [4.01; 23.99], p = 0.01)). Concerning the occurrence of adverse cardiac events and histopathological evaluation, 7 studies showed significantly beneficial outcomes in the intervention group. As for the reduction in overall mortality did not yield a statistically significant result groups (HZ 0.42 (95% CI = [0.15; 1.14]), p = 0.09)). Conclusion: Groups treated with SGLT2i displayed significantly favourable values of ventricular function, lower histopathological changes (vacuolisation, inflammatory infiltration and fibrosis/necrosis), greater cardiac electrical stability with less variation in the QTc interval, fewer reports of adverse cardiac events, lower rate of hospitalisation for heart failure and lower NT-proBNP values. Regarding the reduction in overall mortality due to iSLGT2 in this population, divergent results are presented between studies and in the meta-analysis, making a definitive interpretation not possible.
Introduction: Anthracyclines are highly effective therapeutic agents but are associated with cardiotoxicity. Among the cardiotoxic effects of anthracyclines, a prevalent acute left ventricular dysfunction leading to heart failure stands out. Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) have shown promising results in preventing cardiotoxicity and treating heart failure with reduced ejection fraction. Objective: This meta-analisis aims to evaluate the role of SGLT2i in preventing anthracycline-induced cardiotoxicity. Methods: Pre-clinical and clinical studies involving anthracycline therapy, without a prior diagnosis of heart failure or treatment with SGLT2i, were included. A total of 1858 possible studies were researched, of which ten were selected for inclusion. Results: A significant association favoring the intervention group was found in 6 studies related to left ventricular function (MD 14 (95% CI = [4.01; 23.99], p = 0.01)). Concerning the occurrence of adverse cardiac events and histopathological evaluation, 7 studies showed significantly beneficial outcomes in the intervention group. As for the reduction in overall mortality did not yield a statistically significant result groups (HZ 0.42 (95% CI = [0.15; 1.14]), p = 0.09)). Conclusion: Groups treated with SGLT2i displayed significantly favourable values of ventricular function, lower histopathological changes (vacuolisation, inflammatory infiltration and fibrosis/necrosis), greater cardiac electrical stability with less variation in the QTc interval, fewer reports of adverse cardiac events, lower rate of hospitalisation for heart failure and lower NT-proBNP values. Regarding the reduction in overall mortality due to iSLGT2 in this population, divergent results are presented between studies and in the meta-analysis, making a definitive interpretation not possible.
Descrição
Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2024
Palavras-chave
Cardiotoxicidade Insuficiência cardíaca Inibidores do cotransportador sódio-glicose tipo 2 (SGLT2i) Antraciclinas