Impacto dos polimorfismos CYP2C19*2 e CYP2C19*3 na evolução pós-operatória de pacientes submetidos a procedimentos endovasculares periféricos
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2020-07-24
Autores
Abe, Amanda Hiromi
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Universidade Estadual Paulista (Unesp)
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Introdução - O uso do clopidogrel associado ao ácido acetilsalicílico é o método mais empregado para prevenção da reestenose após o tratamento endovascular. Entretanto, os polimorfismos no gene CYP2C19 estão relacionados com uma redução da transformação do clopidogrel em seu metabólito ativo, com consequente diminuição da eficácia sobre a inibição das plaquetas, resultando em nova obstrução precoce. Objetivo - Fornecer dados sobre a influência dos polimorfismos no gene CYP2C19 na redução da eficácia do clopidogrel e dados epidemiológicos sobre a frequência desses polimorfismos gênicos na população brasileira. Material e métodos - Este foi um estudo retrospectivo de 250 pacientes submetidos à angioplastia de membros inferiores entre os anos de 2015 a 2017. Desses, foram excluídos 153 pacientes, sendo realizado a análise de 97 casos. Resultados e discussão - A patência primária em 1 ano dos territórios ilíaco e fêmoro-poplíteo foram inferiores ao da literatura, 53,83% x 86% (Indes, et al., 2013) e 35,51% x 73% (Almasri et al., 2017), respectivamente, provavelmente porque os pacientes submetidos à angioplastia eram em sua maioria TASC-II C com risco-operatório para cirurgia aberta alto. Sobre o território infra-poplíteo, a patência primária foi semelhante ao da literatura, 60,52% x 66% (Almasri et al., 2017). Para o estudo da associação entre o uso do clopidogrel e a presença de estenose maior que 50% ou oclusão em menos de 1 ano, foi usado o teste do qui-quadrado, porém não houve associação (p=0,5), não sendo possível avaliar a eficácia da medicação no resultado pós-angioplastia periférica. Conclusão - Este trabalho não demonstrou a frequência desses alelos na população brasileira, devido às dificuldades na avaliação das amostras. Novos estudos deverão ser conduzidos para encontrar a melhor metodologia para realizar a análise das amostras e para a avaliação da presença do polimorfismo CYP2C19, a fim de esclarecer melhor a associação entre o uso de clopidogrel e a estenose/oclusão precoce após o tratamento endovascular.
Introduction - Clopidogrel therapy associated with acetylsalicylic acid is the most common method used to prevent restenosis. However, the polymorphism in CYP2C19 gene is related to a reduction in the transformation of clopidogrel to its active metabolite, leading to a reduction in the platelet inhibition, resulting in restenosis or new occlusion. Objective - To provide data on the influence of CYP2C19 polymorphisms gene in reducing the effectiveness of clopidogrel; and to provide epidemiological data on the frequency of CYP2C19 alleles 2 and 3 polymorphisms in the Brazilian population. Methods - This study is retrospective of a database of 250 patients who underwent lower limb angioplasty from 2015 to 2017. There was 153 patients excluded due to exclusion criteria and statistics analysis were performed of 97 patients. Results and discussion- The primary patency in 1 year of the iliac and femoro-popliteal territories were lower than in the literature, 53.83% x 86% (Indes, et al., 2013) and 35.51% x 73% (Almasri et al., 2017 ), respectively, probably because patients undergoing angioplasty were mostly TASC-II C with high operative risk for open surgery. Regarding the infra-popliteal territory, the primary patency was similar to the literature, 60.52% x 66% (Almasri et al., 2017). For the study of the association between the use of clopidogrel and the presence of stenosis greater than 50% or occlusion in less than 1 year, the chi-square test was used, but there was no association (p = 0.5), not being possible to evaluate the effectiveness of the medication in the outcome after peripheral angioplasty. Conclusion - This study could not demonstrate the frequency of this alleles in the Brazilian population, due to difficulties in evaluating the samples. Further studies should be conducted to find a better methodology to perform the sample analysis and to evaluate the presence of CYP2C19 polymorphisms, in order to better clarify an association between the use of clopidogrel and early stenosis/occlusion after endovascular treatment.
Introduction - Clopidogrel therapy associated with acetylsalicylic acid is the most common method used to prevent restenosis. However, the polymorphism in CYP2C19 gene is related to a reduction in the transformation of clopidogrel to its active metabolite, leading to a reduction in the platelet inhibition, resulting in restenosis or new occlusion. Objective - To provide data on the influence of CYP2C19 polymorphisms gene in reducing the effectiveness of clopidogrel; and to provide epidemiological data on the frequency of CYP2C19 alleles 2 and 3 polymorphisms in the Brazilian population. Methods - This study is retrospective of a database of 250 patients who underwent lower limb angioplasty from 2015 to 2017. There was 153 patients excluded due to exclusion criteria and statistics analysis were performed of 97 patients. Results and discussion- The primary patency in 1 year of the iliac and femoro-popliteal territories were lower than in the literature, 53.83% x 86% (Indes, et al., 2013) and 35.51% x 73% (Almasri et al., 2017 ), respectively, probably because patients undergoing angioplasty were mostly TASC-II C with high operative risk for open surgery. Regarding the infra-popliteal territory, the primary patency was similar to the literature, 60.52% x 66% (Almasri et al., 2017). For the study of the association between the use of clopidogrel and the presence of stenosis greater than 50% or occlusion in less than 1 year, the chi-square test was used, but there was no association (p = 0.5), not being possible to evaluate the effectiveness of the medication in the outcome after peripheral angioplasty. Conclusion - This study could not demonstrate the frequency of this alleles in the Brazilian population, due to difficulties in evaluating the samples. Further studies should be conducted to find a better methodology to perform the sample analysis and to evaluate the presence of CYP2C19 polymorphisms, in order to better clarify an association between the use of clopidogrel and early stenosis/occlusion after endovascular treatment.
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Palavras-chave
Angioplastia de membros inferiores, Clopidogrel, Polimorfismo CYP2C19*2, Polimorfismo CYP2C19*3, Lower limb angioplasty, CYP2C19*2 polymorphism, CYP2C19*3 polymorphism