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

dc.contributor.advisorOliveira, Ana Katherine da Silveira Gonçalves de
dc.contributor.advisor-co1Diniz Júnior, José
dc.contributor.advisor-co1Latteshttp://lattes.cnpq.br/7913193754933633pt_BR
dc.contributor.advisorIDhttps://orcid.org/0000-0002-8351-5119pt_BR
dc.contributor.advisorLatteshttp://lattes.cnpq.br/3436756337251449pt_BR
dc.contributor.authorGuimarães, Maria Luisa Nobre Medeiros e Silva
dc.contributor.authorLatteshttp://lattes.cnpq.br/9792315419886174pt_BR
dc.contributor.referees1Eleutério Júnior, José
dc.contributor.referees1IDhttps://orcid.org/0000-0003-4617-7269pt_BR
dc.contributor.referees1Latteshttp://lattes.cnpq.br/7308640728426560pt_BR
dc.contributor.referees2Cobucci, Ricardo Ney de Oliveira
dc.contributor.referees3Piuvezam, Grasiela
dc.contributor.referees3IDhttps://orcid.org/0000-0002-2343-7251pt_BR
dc.contributor.referees3Latteshttp://lattes.cnpq.br/0391780760729166pt_BR
dc.contributor.referees4Freitas, Janaína Cristiana de Oliveira Crispim
dc.contributor.referees4Latteshttp://lattes.cnpq.br/2644540835478572pt_BR
dc.date.accessioned2024-03-13T20:10:32Z
dc.date.available2024-03-13T20:10:32Z
dc.date.issued2024-01-30
dc.description.abstractIntroduction: 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 neededpt_BR
dc.description.resumoObjetivo: 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 tratamentospt_BR
dc.identifier.citationGUIMARÃES, 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 Júniorpt_BR
dc.identifier.urihttps://repositorio.ufrn.br/handle/123456789/57860
dc.languagept_BRpt_BR
dc.publisherUniversidade Federal do Rio Grande do Nortept_BR
dc.publisher.countryBrasilpt_BR
dc.publisher.initialsUFRNpt_BR
dc.publisher.programPROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS DA SAÚDEpt_BR
dc.rightsAcesso Abertopt_BR
dc.subjectApneia obstrutiva do sonopt_BR
dc.subjectTratamento farmacológicopt_BR
dc.subjectPolissonografiapt_BR
dc.subjectRevisão sistemáticapt_BR
dc.subject.cnpqCNPQ::CIENCIAS DA SAUDEpt_BR
dc.titleTerapias farmacológicas com alvo nos endotipos dos pacientes com apneia obstrutiva do sonopt_BR
dc.typedoctoralThesispt_BR

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