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Fluoroquinolones are associated with increased risk of aortic aneurysm or dissection : systematic review and meta-analysis
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Objectivo: As fluoroquinolonas são, actualmente, antibióticos largamente prescritos. Têm emergido preocupações de segurança relativamente ao seu uso – suportadas por estudos in-vitro, animais e epidemiológicos – quanto a potenciais efeitos nocivos em estruturas de colagénio, provocando tendinopatias e descolamento da retina. Mais recentemente, um associação de risco tem sido estabelecida quanto a aneurismas e dissecções/ruturas da aorta (AA ou AD/AR), ambas condições graves ou mesmo potencialmente fatais. Assim, elaborámos uma revisão sistemática para avaliar o efeito do uso de fluoroquinolonas no risco de desenvolvimento de AA ou AD/AR.
Métodos: As bases de dados MEDLINE, Web of Science Core Collection e Cochrane Central Register of Controlled Trials (Março 2019) foram pesquisadas por estudos longitudinais avaliando o uso de fluoroquinolonas comparado com o uso de outros antibióticos ou com não-tratamento, em doentes co m AA ou AD/AR. O risco de viés foi determinado através da ferramenta ROBINS-I. Realizámos uma meta-análise de efeitos aleatórios para estimar os agregados odds ratio com IC 95%, e a heterogeneidade foi avaliada usando a estatística I2.
Resultados: Sete estudos observacionais, contemplando designs variados, avaliando aproximadamente 1 024 984 doentes com AA ou AD/AR, foram incluídos na meta-análise. O uso de fluoroquinolonas foi associado com um maior risco de AA ou AD/AR, em comparação com a intervenção de não-tratamento (OR=2.26; 95% CI 1.93 to 2.65; I2=30%) e em comparação com a intervenção de uso de beta-lactâmico (OR=1.56; 95% CI 1.37 to 1.79; I2=0%). O efeito lesivo do uso de fluoroquinolonas permaneceu positivo e estatisticamente significativo quando foram agregados os resultados para o desfecho AD/AR apenas e agregando por design do estudo. Foi considerado que os desfechos dos estudos que utilizaram comparação com beta-lactâmicos têm risco de viés moderado, enquanto que foi considerado que os restantes têm pelo menos um grave risco de viés. Todos os desfechos avaliados têm uma muito baixa qualidade de evidência e força de recomendação (GRADE).
Conclusão: O uso de fluoroquinolonas foi associado com um risco significativo de desenvolvimento de AA ou AD/AR.
Objective: Fluoroquinolones are currently widely prescribed antibiotics. Safety concerns regarding its use have been emerging, on a potential harm effect on collagenous structures, leading to tendinopathy and retinal detachment. More recently, a risk association has been established for aortic aneurysm and aortic dissection or rupture (AA or AD/AR), both being serious, or even life-threatening, conditions. Therefore, we conducted a systematic review to evaluate the effect of fluoquinolones use in the risk of developing AA or AD/AR. Methods: MEDLINE, Web of Science Core Collection and Cochrane Central Register of Controlled Trials databases (March 2019) were searched for longitudinal studies evaluating fluoroquinolones use compared with other antibiotic use or with non-treatment, in patients with AA or AD/AR. The risk of bias was assessed through the ROBINS-I tool. We performed a random-effects meta-analysis to estimate the pooled odds ratio’s with 95% CI’s, and heterogeneity was evaluated using the I2 statistics. Results: Seven observational studies, comprising different designs, evaluating approximately 1 024 984 patients with AA or AD/AR were included in the meta-analysis. Fluoroquinolones use was associated with a higher risk of AA or AD/AR, comparing with a non-treatment intervention (OR=2.26; 95% CI 1.93 to 2.65; I2=30%) and comparing with a beta-lactam intervention (OR=1.56; 95% CI 1.37 to 1.79; I2=0%). The harm effect of the fluoroquinolone use remained positive and statistically significant when pooling the results for the AD/AR outcome only and when pooling according to study design. The outcomes of the studies using beta-lactam comparison were considered to have a moderate risk of bias, while the remaining ones were classified as having at least a serious risk of bias. All evaluated outcomes had very low Grading of Recommendation, Assessment, Development and Evaluation (GRADE) evidence. Conclusion: Fluoroquinolone use was associated with a significant risk of AA or AD/AR.
Objective: Fluoroquinolones are currently widely prescribed antibiotics. Safety concerns regarding its use have been emerging, on a potential harm effect on collagenous structures, leading to tendinopathy and retinal detachment. More recently, a risk association has been established for aortic aneurysm and aortic dissection or rupture (AA or AD/AR), both being serious, or even life-threatening, conditions. Therefore, we conducted a systematic review to evaluate the effect of fluoquinolones use in the risk of developing AA or AD/AR. Methods: MEDLINE, Web of Science Core Collection and Cochrane Central Register of Controlled Trials databases (March 2019) were searched for longitudinal studies evaluating fluoroquinolones use compared with other antibiotic use or with non-treatment, in patients with AA or AD/AR. The risk of bias was assessed through the ROBINS-I tool. We performed a random-effects meta-analysis to estimate the pooled odds ratio’s with 95% CI’s, and heterogeneity was evaluated using the I2 statistics. Results: Seven observational studies, comprising different designs, evaluating approximately 1 024 984 patients with AA or AD/AR were included in the meta-analysis. Fluoroquinolones use was associated with a higher risk of AA or AD/AR, comparing with a non-treatment intervention (OR=2.26; 95% CI 1.93 to 2.65; I2=30%) and comparing with a beta-lactam intervention (OR=1.56; 95% CI 1.37 to 1.79; I2=0%). The harm effect of the fluoroquinolone use remained positive and statistically significant when pooling the results for the AD/AR outcome only and when pooling according to study design. The outcomes of the studies using beta-lactam comparison were considered to have a moderate risk of bias, while the remaining ones were classified as having at least a serious risk of bias. All evaluated outcomes had very low Grading of Recommendation, Assessment, Development and Evaluation (GRADE) evidence. Conclusion: Fluoroquinolone use was associated with a significant risk of AA or AD/AR.
Descrição
Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2020
Palavras-chave
Fluoroquinolonas Aneurisma da aorta Dissecção da aorta Revisão sistemática Meta-análise