ABSTRACT
We analysed clinical and pharmacological factors influencing resistance to clopidogrel in 250 patients with cardiovascular diseases during 18 months. It was shown that the risk ofresistance depends on the form of coronary heart disease, carbohydrate metabolism, the AA genotype of CYP2C19*2 and TBS1 genes. The cardiovascular events significantly morefrequently occurred during 12 and 18 months in resistant diabetics and in the patients with an allele lacking the *2/*3 CYP2C9 gene function and AT/TT polymorphism of the thromboxane synthase gene TBS1.
Subject(s)
Cardiovascular Diseases/drug therapy , Cytochrome P-450 CYP2C19/genetics , DNA/genetics , Drug Resistance/genetics , Polymorphism, Genetic , Thromboxane-A Synthase/genetics , Ticlopidine/analogs & derivatives , Alleles , Cardiovascular Diseases/metabolism , Clopidogrel , Cytochrome P-450 CYP2C19/metabolism , Female , Genotype , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors/therapeutic use , Retrospective Studies , Thromboxane-A Synthase/metabolism , Ticlopidine/therapeutic useABSTRACT
AIM: To analyze the influence of clinical and pharmacogenetic factors on the risk of resistance to original or generic clopidogrel and that of cardiovascular events (CVE) during 12 months of follow-up. SUBJECTS AND METHODS: Two hundred and fifty patients admitted to Moscow hospitals in October 2011 to September 2012 were examined. All the patients received clopidogrel. During their stay at hospital, venous blood samples were collected twice (before and 7-10 days after continuous clopidogrel intake). Platelet function was determined by optical aggregometry. A less than 10% reduction in platelet aggregation was taken as a resistance criterion. In addition, CYP2C9 and CYP2C19 gene polymorphisms were investigated. RESULTS: Whether original or generic clopidogrel is used, the level of baseline or post-7-day ADP-induced platelet aggregation (ADP aggregation) fails to affect the risk of its resistance. Evaluation of ADP-induced platelet aggregation in patients with different CYP2C9 and CYP2C19 gene polymorphisms during the administration of original or generic clopidogrel also showed no significant differences in its resistance. During the 12-month follow-up, CVE significantly less frequently occurred as a result of the intake of original versus generic clopidogrel. CONCLUSION: The use of original clopidogrel does not affect the risk of resistance to antiplatelet drugs, but it is associated with the lower incidence of CVE during a year.
