Terapias farmacológicas com alvo nos endotipos dos pacientes com apneia obstrutiva do sono

Introduction: Sleep is crucial for the proper functioning of the human body. Sleep disorders can significantly impact the quality of life and increase the risk of cardiometabolic, psychiatric, and cognitive diseases. Obstructive sleep apnea (OSA) is characterized by repetitive partial or complete co...

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Autor principal: Guimarães, Maria Luisa Nobre Medeiros e Silva
Outros Autores: Oliveira, Ana Katherine da Silveira Gonçalves de
Formato: doctoralThesis
Idioma:pt_BR
Publicado em: Universidade Federal do Rio Grande do Norte
Assuntos:
Apneia obstrutiva do sono
Tratamento farmacológico
Polissonografia
Revisão sistemática
CNPQ::CIENCIAS DA SAUDE
Endereço do item:https://repositorio.ufrn.br/handle/123456789/57860
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id ri-123456789-57860
record_format dspace
institution Repositório Institucional
collection RI - UFRN
language pt_BR
topic Apneia obstrutiva do sono
Tratamento farmacológico
Polissonografia
Revisão sistemática
CNPQ::CIENCIAS DA SAUDE
spellingShingle Apneia obstrutiva do sono
Tratamento farmacológico
Polissonografia
Revisão sistemática
CNPQ::CIENCIAS DA SAUDE
Guimarães, Maria Luisa Nobre Medeiros e Silva
Terapias farmacológicas com alvo nos endotipos dos pacientes com apneia obstrutiva do sono
description Introduction: Sleep is crucial for the proper functioning of the human body. Sleep disorders can significantly impact the quality of life and increase the risk of cardiometabolic, psychiatric, and cognitive diseases. Obstructive sleep apnea (OSA) is characterized by repetitive partial or complete collapse of the upper airway during sleep. While positive airway pressure therapy is the primary treatment, its low compliance rate has prompted exploration into alternative approaches. Recent physiological studies about the disease’s mechanisms brought the possibility of therapeutic targets for pharmacotherapy. Objective: This study aims to assess and summarize the scientific evidence regarding the efficacy and safety of drug therapies in alleviating the severity of obstructive sleep apnea in adults. Methods: One protocol and two systematic reviews, one incorporating network meta-analysis, were conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. A comprehensive search strategy retrieved relevant randomized clinical trials on drug treatments assessing the primary outcome apnea-hypopnea index (AHI) in adult patients with obstructive sleep apnea, from databases: PubMed, Embase, Web of Science, SciELO, LILACS, Scopus, Cochrane Register of Controlled Trials, and ClinicalTrials.gov. Two authors independently selected studies and extracted data. The Cochrane Risk of Bias tool 2 assessed the risk of bias. Pairwise meta-analysis used RevMan 5.4, while network meta-analysis utilized the netmeta package in R Studio. Results: Among the 4930 articles obtained, 68 met the inclusion criteria. A total of 29 studies, involving 11 drugs, were included in the meta-analysis. Notable findings include Atomoxetine plus oxybutynin vs placebo, demonstrating a mean difference in AHI of -7.71 (-10.59, -4.83) [Fixed, 95% CI, I2= 50%, overall effect: Z = 5.25, p<0.001]. Donepezil vs placebo exhibited a mean difference in AHI of -8.56 (-15.78, -1.33) [Fixed, 95% CI, I2= 21%, overall effect: Z= 2.32, p=0.02]. Sodium oxybate vs placebo resulted in a mean difference in AHI of -5.50 (-9.28, -1.73) [Fixed, 95% CI, I2= 32%, overall effect: Z = 2.86, p=0.004]. Trazodone vs placebo displayed a mean difference in AHI of -12.75 (-21.30, -4.19) [Fixed, 95% CI, I2= 0%, overall effect: Z = 2.92, p=0.003]. In the network meta-analysis, multiple treatments targeting muscle responsiveness in adults with obstructive sleep apnea were compared, with five interventions showing a statistically significant reduction in apnea-hypopnea index compared to placebo. Conclusions: Acetazolamide, reboxetine plus oxybutynin, atomoxetine plus oxybutynin, atomoxetine plus aroxybutynin, atomoxetine alone, donepezil, sodium oxybate and trazodone showed statistically significant reduction in AHI. The combination of noradrenergic and antimuscarinic agents emerges as the most promising drug treatment targeting muscle responsiveness. The path towards precision medicine in treating obstructive sleep apnea involves understanding endotypes, phenotypes, and developing relevant metrics. More studies to assess clinical significance, adverse events and sustained effects of these treatments in larger populations and with longer follow-ups are needed
author2 Oliveira, Ana Katherine da Silveira Gonçalves de
author_facet Oliveira, Ana Katherine da Silveira Gonçalves de
Guimarães, Maria Luisa Nobre Medeiros e Silva
format doctoralThesis
author Guimarães, Maria Luisa Nobre Medeiros e Silva
author_sort Guimarães, Maria Luisa Nobre Medeiros e Silva
title Terapias farmacológicas com alvo nos endotipos dos pacientes com apneia obstrutiva do sono
title_short Terapias farmacológicas com alvo nos endotipos dos pacientes com apneia obstrutiva do sono
title_full Terapias farmacológicas com alvo nos endotipos dos pacientes com apneia obstrutiva do sono
title_fullStr Terapias farmacológicas com alvo nos endotipos dos pacientes com apneia obstrutiva do sono
title_full_unstemmed Terapias farmacológicas com alvo nos endotipos dos pacientes com apneia obstrutiva do sono
title_sort terapias farmacológicas com alvo nos endotipos dos pacientes com apneia obstrutiva do sono
publisher Universidade Federal do Rio Grande do Norte
publishDate 2024
url https://repositorio.ufrn.br/handle/123456789/57860
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spelling ri-123456789-578602024-03-18T20:16:26Z Terapias farmacológicas com alvo nos endotipos dos pacientes com apneia obstrutiva do sono Guimarães, Maria Luisa Nobre Medeiros e Silva Oliveira, Ana Katherine da Silveira Gonçalves de http://lattes.cnpq.br/9792315419886174 https://orcid.org/0000-0002-8351-5119 http://lattes.cnpq.br/3436756337251449 Diniz Júnior, José http://lattes.cnpq.br/7913193754933633 Eleutério Júnior, José https://orcid.org/0000-0003-4617-7269 http://lattes.cnpq.br/7308640728426560 Cobucci, Ricardo Ney de Oliveira Piuvezam, Grasiela https://orcid.org/0000-0002-2343-7251 http://lattes.cnpq.br/0391780760729166 Freitas, Janaína Cristiana de Oliveira Crispim http://lattes.cnpq.br/2644540835478572 Apneia obstrutiva do sono Tratamento farmacológico Polissonografia Revisão sistemática CNPQ::CIENCIAS DA SAUDE Introduction: Sleep is crucial for the proper functioning of the human body. Sleep disorders can significantly impact the quality of life and increase the risk of cardiometabolic, psychiatric, and cognitive diseases. Obstructive sleep apnea (OSA) is characterized by repetitive partial or complete collapse of the upper airway during sleep. While positive airway pressure therapy is the primary treatment, its low compliance rate has prompted exploration into alternative approaches. Recent physiological studies about the disease’s mechanisms brought the possibility of therapeutic targets for pharmacotherapy. Objective: This study aims to assess and summarize the scientific evidence regarding the efficacy and safety of drug therapies in alleviating the severity of obstructive sleep apnea in adults. Methods: One protocol and two systematic reviews, one incorporating network meta-analysis, were conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. A comprehensive search strategy retrieved relevant randomized clinical trials on drug treatments assessing the primary outcome apnea-hypopnea index (AHI) in adult patients with obstructive sleep apnea, from databases: PubMed, Embase, Web of Science, SciELO, LILACS, Scopus, Cochrane Register of Controlled Trials, and ClinicalTrials.gov. Two authors independently selected studies and extracted data. The Cochrane Risk of Bias tool 2 assessed the risk of bias. Pairwise meta-analysis used RevMan 5.4, while network meta-analysis utilized the netmeta package in R Studio. Results: Among the 4930 articles obtained, 68 met the inclusion criteria. A total of 29 studies, involving 11 drugs, were included in the meta-analysis. Notable findings include Atomoxetine plus oxybutynin vs placebo, demonstrating a mean difference in AHI of -7.71 (-10.59, -4.83) [Fixed, 95% CI, I2= 50%, overall effect: Z = 5.25, p<0.001]. Donepezil vs placebo exhibited a mean difference in AHI of -8.56 (-15.78, -1.33) [Fixed, 95% CI, I2= 21%, overall effect: Z= 2.32, p=0.02]. Sodium oxybate vs placebo resulted in a mean difference in AHI of -5.50 (-9.28, -1.73) [Fixed, 95% CI, I2= 32%, overall effect: Z = 2.86, p=0.004]. Trazodone vs placebo displayed a mean difference in AHI of -12.75 (-21.30, -4.19) [Fixed, 95% CI, I2= 0%, overall effect: Z = 2.92, p=0.003]. In the network meta-analysis, multiple treatments targeting muscle responsiveness in adults with obstructive sleep apnea were compared, with five interventions showing a statistically significant reduction in apnea-hypopnea index compared to placebo. Conclusions: Acetazolamide, reboxetine plus oxybutynin, atomoxetine plus oxybutynin, atomoxetine plus aroxybutynin, atomoxetine alone, donepezil, sodium oxybate and trazodone showed statistically significant reduction in AHI. The combination of noradrenergic and antimuscarinic agents emerges as the most promising drug treatment targeting muscle responsiveness. The path towards precision medicine in treating obstructive sleep apnea involves understanding endotypes, phenotypes, and developing relevant metrics. More studies to assess clinical significance, adverse events and sustained effects of these treatments in larger populations and with longer follow-ups are needed Objetivo: sumarizar as evidências a respeito das terapias medicamentosas para a apneia obstrutiva do sono. Métodos: Foram seguidas as diretrizes do Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Foram realizadas buscas no PubMed, Embase, Scopus, Web of Science, SciELO, LILACS, Scopus, Cochrane Central Register of Controlled Trials e ClinicalTrials.gov em 17 de fevereiro de 2023. Uma estratégia de busca foi usada para identificar ensaios clínicos randomizados comparando o índice de apneia-hipopneia (IAH) em farmacoterapias. Estudos foram selecionados e os dados foram extraídos por dois autores de forma independente. O risco de viés foi avaliado usando a ferramenta Cochrane Risk of Bias. O RevMan 5.4 foi usado para síntese de dados. Resultados: Foram obtidos 4930 artigos, 68 atenderam aos critérios de inclusão e 29 estudos (envolvendo 11 medicamentos) foram combinados em meta-análise. Atomoxetina mais oxibutinina vs placebo teve uma diferença média no IAH de -7,71 (-10,59, -4,83) [Fixo, IC 95%, I2= 50%, effect size: Z = 5,25, p<0,001]. Donepezila vs placebo teve uma diferença média no IAH de -8,56 (-15,78, -1,33) [Fixo, IC 95%, I2= 21%, effect size: Z= 2,32, p=0,02]. Oxicarbonato de sódio vs placebo teve uma diferença média no IAH de -5,50 (-9,28, -1,73) [Fixo, IC 95%, I2= 32%, effect size: Z = 2,86, p=0,004]. Trazodona vs placebo teve uma diferença média no IAH de -12,75 (-21,30, -4,19) [Fixo, IC 95%, I2= 0%, effect size: Z = 2,92, p=0,003]. Conclusão: A combinação de medicamentos noradrenérgicos e antimuscarínicos apresenta resultados promissores. Identificar endótipos pode ser a chave para futuras terapias medicamentosas para a apneia obstrutiva do sono. Além disso, são necessários estudos com acompanhamento mais longo para avaliar a segurança e os efeitos sustentados desses tratamentos 2024-03-13T20:10:32Z 2024-03-13T20:10:32Z 2024-01-30 doctoralThesis GUIMARÃES, Maria Luisa Nobre Medeiros e Silva. Terapias farmacológicas com alvo nos endotipos dos pacientes com apneia obstrutiva do sono. 2024. 136f. Orientação: Ana Katherine da Silveira Gonçalves de Oliveira. Coorientação: José Diniz Júnior. Tese (doutorado) - Universidade Federal do Rio Grande do Norte, Centro de Ciências da Saúde, Programa de Pós-graduação em Ciências da Saúde. Natal, RN, 2024. Coorientação: José Diniz Júnior https://repositorio.ufrn.br/handle/123456789/57860 pt_BR Acesso Aberto application/pdf Universidade Federal do Rio Grande do Norte Brasil UFRN PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS DA SAÚDE

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