OBJECTIVES: The aim of this study was to provide in depth analysis of genetic and non-genetic factors that influence clopidogrel efficacy in cardiology patients.

METHODS: We have conducted a prospective study in 200 hospitalized patients. CYP2C19 genetic testing was conducted, and the PREDICT score was calculated in 102 out of 200 patients treated with clopidogrel in order to determine the influence of genetic and non-genetic factors on outcomes of interest. Adverse cardiovascular events and adverse reactions to clopidogrel were assessed during 12 months follow up period.

RESULTS: In univariate logistic regression model, statistically significant predictors of the outcome of interest are: the PREDICT score (p <0.001), enzymatic activity [slow metabolizers (p<0.001) compared to the rapid, extensive and intermediate metabolizers as a reference category] and concomitant use of other drugs that are also metabolized through CYP2C19 (p = 0.030): pantoprazole, omeprazole, diazepam, warfarin, and gliclazide. In multivariate logistic regression model, predictors from the model of univariate logistic regression which were statistically significant at the significance level of 0.05 were included. The model contains three predictors - PREDICT score, enzymatic activity and concomitant administration of other drugs that are metabolized via the same CYP enzyme. The whole model was statistically significant (p < 0.001). There is no significant multicollinearity or interaction between the predictors (p = 0.002 and 0.009, respectively).

CONCLUSIONS: The stepwise approach could be used in assessing the clopidogrel resistance in cardiology patients, combining the PREDICT score, platelet aggregation test, and genetic testing for CYP2C19 polymorphism.