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• W4253478275 abstract "Clopidogrel requires oxidation dependent on the cytochrome P450 enzyme 2C19 (CYP2C19) to form its active metabolite. The importance of loss-of-function alleles (particularly CYP2C19*2, 681G>A) in poor platelet response to clopidogrel is well recognized. To investigate the prevalence and prognostic impact of the CYP2C19*2 allele in a local acute coronary syndrome (ACS) population. We performed a prospective, longitudinal study of 95 patients admitted for an ACS between March and October 2009 to a single coronary care unit. Patients aged under 75 who survived hospital stay and for whom clopidogrel was prescribed were included. At discharge, CYP2C19 was genotyped using a commercially available kit. Patients were divided into two groups: Group A (non-carriers, normal metabolizers, CYP2C19*1/*1), n = 69; and Group B (carriers, slow metabolizers, CYP2C19*2/*1 or *2/*2), n = 26. The primary endpoint was a combined outcome of cardiovascular death, non-fatal myocardial infarction or re-admission for unstable angina; median follow-up was 136.0 (79.0–188.0) days. The median age of the population was 62.0 (51.0–68.0) years, and 83.2% were male. The CYP2C19*2 (A) allele had a frequency of 14.2%. There were no differences between the groups with respect to demographic data or history of cardiovascular disease. Coronary anatomy, left ventricular ejection fraction and renal function were also similar. The groups were also homogenous with respect to GRACE risk score (118.0 (95.0–136.5) vs. 115.0 (96.0–133.0), p = 0.68), medical treatment and percutaneous revascularization during hospital stay. Event-free survival was higher for Group A (94.0% vs. 75.0%, log-rank p = 0.010). Three readmissions for MI were documented, all in the slow metabolizers group. In our ACS population, the CYP2C19*2 allele was a medium-term prognostic marker. Polimorfismos no complexo enzimático P450, como CYP2C19*2, 681G>A parecem estar na base de fraca resposta ao clopidogrel. Caracterizar a prevalência e o impacto prognóstico do alelo CYP2C19*2(A) numa população local de doentes com síndrome coronária aguda (SCA). Estudo longitudinal, prospectivo, de 95 doentes admitidos por SCA entre Março e Outubro de 2009. Foram incluídos doentes com idade inferior a 75 anos, que sobreviveram à hospitalização, e que tiveram alta medicados com clopidogrel. Foi determinado o genótipo do alelo CYP2C19 no momento da alta hospitalar. Foram criados dois grupos; grupo A (metabolizadores normais, CYP2C19 *1/*1) n = 69 e grupo B (metabolizadores lentos, CYP2C19 *2/*1 ou *2/*2) n = 26. No seguimento foi analisado um resultado combinado de morte cardiovascular, enfarte agudo do miocárdio não fatal, e readmissão por angina instável (tempo mediano de seguimento: 136 (79–188) dias. A idade mediana da população era de 62,0 (51,0–68,0) anos, e 83,2% eram do género masculino. O alelo CYP2C19*2(A) teve uma frequência de 14,2%. Não existiram diferenças entres os grupos relativamente a dados demográficos, e antecedentes cardiovasculares. A anatomia coronária, a fracção de ejecção ventricular esquerda e a função renal eram semelhantes. Os grupos eram também homogéneos relativamente ao score GRACE (118,0 (95,0–136,5) versus 115,0 (96,0–133,0), p = 0,68), tratamento médico e taxa de revascularização percutânea durante hospitalização. No final do seguimento clínico a sobrevida livre de eventos foi superior para o grupo A (94,0% versus 75,0%, log rank p = 0,010). Foram documentadas três readmissões por enfarte agudo do miocárdio, todas no grupo B. Na população referida, o alelo CYP2C19*2 (A) foi um marcador de prognóstico a médio prazo." @default.
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• W4253478275 date "2012-04-01" @default.
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• W4253478275 title "CYP2C19*2 and prognosis after an acute coronary syndrome: Insights from a Portuguese center" @default.
• W4253478275 doi "https://doi.org/10.1016/j.repce.2012.04.001" @default.
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