Moderated Poster Session III: Basic science

P151 Cytochrome P450 2c19 polymorphism and cardiovascular recurrences in patients under clopidogrel treatment: a meta-analysis F Sofi, B Giusti, AM Gori, F Cesari, R Marcucci, R Abbate, GF Gensini University of Florence, Florence, Italy Topic: Genetic-environmental interactions Introduction: Nonresponsiveness to clopidogrel has been reported to be an independent predictor of clinical recurrences in patients with coronary artery disease under clopidogrel treatment. Recently, several polymorphisms in gene encoding platelet components or cytochrome P450 (CYP) enzymes have been proposed as possible mechanisms for nonresponsiveness to clopidogrel. Among them, a great deal of attention has been posed on a loss-of-function CYP2C19 2 (or 681 G>A) polymorphism. To evaluate the role of such polymorphism in recurrent atherothrombotic events in patients with CAD under clopidogrel treatment, we considered all available studies in a meta-analysis. Material and Methods: Cohort prospective studies evaluating the association between CYP2C19 2 polymorphism and adverse clinical outcome were searched in MEDLINE, EMBASE, Web of Science, The Cochrane Systematic Review Database and bibliographies of retrieved articles up to January, 2009. The principal prior hypothesis was that the presence of the 2 variant allele of the polymorphism would be associated with an increased risk of clinical recurrence. Results: Data were available for a total of 7,950 patients from 6 cohort prospective studies who were followed for a time ranging from 6 months to 8.4 years. The summary risk ratios for included cohort prospective studies showed a significant association between the CYP2C19 2 polymorphism and an increased risk of major adverse cardiac events in the follow-up [RR: 1.80 (1.02-3.19); p1⁄40.04].When studies evaluating stent thrombosis (n1⁄44) for a total of 4,975 patients were considered, the presence of the variant allele was associated with an increased risk of stent thrombosis [RR: 2.82 (1.43-5.56); p1⁄40.0001]. Conclusion: The present meta-analysis performed on nearly 8,000 patients with CAD under clopidogrel treatment shows that the CYP2C19 2 polymorphism is associated with an increased risk of major adverse cardiac events and stent thrombosis. These results need to be confirmed by further studies.