Abstract 10265: Different Influences of CYP2C19 Gene Polymorphisms on Antiplatelet Effect of Clopidogrel and Ticlopidine
Background: The antiplatelet effect of clopidogrel, but not ticlopidine, is reported to be affected by CYP2C19 polymorphisms. The incidence of CYP2C19 polymorphism is relatively higher in Japanese. It is important to establish individualized antiplatelet therapies based on the CYP2C19 polymorphisms. The purpose of this study was to examine the influence of CYP2C19 polymorphisms on the antiplatelet effect of clopidogrel and ticlopidine.
Methods: The platelet aggregations induced by 20μmol/L ADP and single nucleotide polymorphisms of CYP2C19*2 and *3 were evaluated in 165 coronary artery disease (CAD) patients taking aspirin (100 mg/day) (n = 21), aspirin plus clopidogrel (75 mg/day) (n = 97), or aspirin plus ticlopidine (200 mg/day) (n = 47).
Results: The degree of platelet aggregation in patients with clopidogrel depended on CYP2C19 polymorphisms as follows: extensive metabolizers (EM: *1/*1) < intermediate metabolizers (IM: *1/*2 and *1/*3) < poor metabolizers (PM: *2/*2, *2/*3 and *3/*3). In PM patients, the maximal platelet aggregation with aspirin plus clopidogrel was equivalent to that with aspirin alone. Meanwhile, platelet aggregation in patients with ticlopidine did not depend on CYP2C19 polymorphisms, and the degree of the variable was significantly lower than that in PM patients with clopidogrel. When 7 PM patients treated with clopidogrel were switched to ticlopidine, the platelet aggregations were significantly suppressed in all patients. (the residual platelet aggregation: 33.4% vs 17.3%, p < 0.01).
Conclusions: This study showed that CYP2C19 polymorphisms had a profound impact on the antiplatelet effect of clopidogrel, but not ticlopidine. Ticlopidine might be an effective therapeutic option for patients with CYP2C19 PM.
- © 2010 by American Heart Association, Inc.