037 The relative contribution of the CYP2C19*2 polymorphism in the low responsiveness to clopidogrel in the VASP-02 study

The CYP2C19*2 genetic variant is known to contribute to low responsiveness to clopidogrel treatment, leading to a higher rate of cardiovascular events. Systematic identification of the 2C19*2 carriers to predict the individual patient's response to clopidogrel is a matter of debate. Data of the VASP-02 study comparing patients’ responsiveness to 75 and 150 mg/day maintenance dose of clopidogrel (Aleil et al., J Am Coll Cardiol Intv 2008) were reanalyzed by determining the 2C19*2 carrier status of the patients. Platelet reactivity index (PRI) was determined using the VASP method. A PRI>69% defines low responsiveness to clopidogrel. In the 37 non responder patients, 42.4% were 2C19*2 carriers versus 22.0% in the responder patients (p=0.022). After multivariate analysis, 2C19*2 polymorphism and high body weight were two independent predictors of high PRI (odds ratio [95% confidence interval] 3.39 [1.06-10.84] p=0.039 and 3.14 [1.19-8.30] p=0.021) respectively. Increasing the maintenance dose of clopidogrel from 75 to 150 mg/day in non responder patients resulted in a significant decrease of PRI from 76.4±4.6 to 62.8±10.4% (p CYP2C19*2 is an important determinant of the responsiveness to clopidogrel while other independent factors such as body weight also are involved. Hyporesponsiveness in 2C19*2 carriers can be easily overcome by doubling the maintenance dose of clopidogrel. Thus, combined functional pharmacodynamic monitoring and genetic determination of CYP profile should help improve patient's responsiveness to clopidogrel.