TITLE:
CYP2C19 (+ or －)*2/(+ or －)*17 Diplotypes: Prognostic impactson patients with acute coronary syndrome
AUTHORS:
Rogério Teixeira, Manuela Grazina, Pedro Monteiro, Francisco Soares, Margarida Lourenço, Guilherme Pêgo
KEYWORDS:
CYP2C19*2/CYPC2C19*17 Combination; Clopidogrel; Acute Coronary Syndrome; Prognosis
JOURNAL NAME:
World Journal of Cardiovascular Diseases,
Vol.2 No.4,
October
30,
2012
ABSTRACT: Purpose: To investigate the prognostic impacts of a combined clopidogrel-metabolizing genotypes CYP 2C19 (+ or －)*2/(+ or －)*17 on patients with acute coronary syndrome (ACS). Population and methods: Prospective, longitudinal study of 95 patients admitted for ACS to a single coronary care unit. Patients less than 75 years of age, who survived hospitalization and to whom clopidogrel was prescribed, were included. CYP2C19 genotyping was performed at dis- charge. For analysis, the patients were grouped as follows: Group A ([+]*2/[+]*17) n = 8; Group B ([+]*2/[－]*17) n = 18; Group C ([－]*2/[+]*17) n = 27; and Group D ([－]*2/[－]*17) n = 42. Platelet function was assessed by an ADP platelet aggregation test using a commercially available kit. The primary end-point was a composite of mortality or readmission for ACS. The median time of follow-up was 136.0 (79.0 － 188.0) days. Results: The mean age of the study patients was 59.9 ± 10.7 years, and 83.2% were male. The allele frequencies of CYP2C19*2 and CYP2C19 *17 were 14.2% and 20%, respectively. Both allele frequencies were in Hardy Weinberg equilibrium. The patient groups were homogenous for demographic data, cardiovascular risk factors, GRACE and CRUSADE bleeding scores, left ventricular ejection fraction, and coronary anatomy. ADP platelet aggre-gation was similar for all groups (respective rates for groups A, B, C, D were 17.5 U (10.3 – 18.7) vs 20.0 U (17.3 – 26.8) vs 16 U (12 – 19) vs 12 U (8 – 22), p = 0.4). Event-free survival was significantly lower for group B (respective rates for Groups A, B, C, D were 87.5% vs 68.8% vs 96.3% vs 92.5%; p = 0.02). By multivariate Cox regression analysis, the CYP2C19 (+)*2/(－)*17 diplotype was an independent predictor of outcome, conferring a 5.2-fold higher adjusted risk for the composite endpoint than the others diplotypes. Conclusion: In our study, patients with the intermediate plus non-ultrarapid clopidogrel-metabolizing genotype ([+]*2/[－]*17) had a significantly poor medium-term prognosis for ischemic events, compared with the other diplotypes.