Factors that contribute to clopidogrel resistance in cardiovascular disease patients: environmental and genetic approach

Background and objective: Clopidogrel is a potent antiplatelet drug that reduces the risk of vascular events in patients with cardiovascular disease. However, several studies have shown that about a quarter of patients showed low or no response to clopidogrel therapy. In this study, factors that contribute to clopidogrel resistance were investigated in 270 cardiovascular disease patients from Jordan. Patients and methods: Clopidogrel resistance was determined through platelet aggregation analysis using the Multiplate analyzer. Genetic factors (CYP2C19*2 and PON1 Q192R) were examined using polymerase chain reaction-restriction fragment length polymorphism analysis. Results: The incidence of clopidogrel resistance among Jordanians is similar to 32%. Significant association between clopidogrel resistance and female gender, concomitant use of calcium channel blockers, and low HDL was found (p < 0.05). In addition, presence of CYP2C19*2 allele is strongly related to clopidogrel resistance (p < 0.001). However, lack of contribution to clopidogrel resistance was found for PON1 Q192R polymorphism, age, diabetes, hypertension, smoking and aspirin use (p > 0.05). Conclusion: Several factors might contribute to clopidogrel resistance including gender, concomitant use of calcium channel blockers, HDL and CYP2C19*2 polymorphism.