Abstract 5013: Body Mass Index is the Main Determinant of High On-treatment Platelet Reactivity and of Failed Dose Adjustment According to Platelet Reactivity Monitoring

Abstract

High on-treatment platelet reactivity(HTPR) after clopidogrel loading dose(LD) predicts the risk of thrombotic events after percutaneous coronary intervention(PCI). We have demonstrated that HTPR could be overcome in the majority of cases using dose-adjustment according to PR monitoring resulting in an improved clinical outcome. However this strategy failed in 10% of patients with HTPR. Cytochromes(CYP)2C19 polymorphism is a major determinant of the response to clopidogrel and could be responsible for dose-adjustment failure. We aimed to determine predictors of a failure of the dose-adjustment strategy. Seventy-three patients undergoing PCI were included in this prospective multicentre study. A VASP index ≥ 50% after a 600mg LD of clopidogrel defined HTPR. Dose-adjustment was performed according to PR monitoring to reach a VASP index < 50%. Genetic polymorphism of CYP2C19 was determined by direct sequencing. Clinical predictors of HTPR were BMI(p=0.01), diabetes(p=0.03) and acute coronary syndrome(p=0.02). The mutant 2* allele of CYP2C19 681A>G loss of function polymorphism was also significantly associated with HTPR(p=0.04). The rate of successful dose adjustment was similar in carriers of the CYP2C19*2 allele and carriers of the wild-type allele. The only independent predictor of a failed dose-adjustment was a high BMI(p=0.01). In conclusion, high BMI, acute coronary syndrome, diabetes and CYP2C19*2 are associated with HTPR after a 600mg LD of clopidogrel. Dose-adjustment overcomes HTPR in carriers of the CYP2C19*2 allele. BMI is the only independent predictor of failed dose adjustment. Thus drug under-dosage seems to be the main determinant of HTPR.