Key result
CYP2C19 polymorphisms significantly reduced the antiplatelet effect of clopidogrel, but not ticlopidine, with poor metabolizers on clopidogrel showing aggregation equivalent to aspirin alone.
Why the study?
Do CYP2C19 gene polymorphisms differentially impact the antiplatelet effects of clopidogrel and ticlopidine in patients with coronary artery disease?
Observational (n=165)
Do CYP2C19 gene polymorphisms differentially impact the antiplatelet effects of clopidogrel and ticlopidine in patients with coronary artery disease?
CYP2C19 poor metabolizers have a significantly reduced antiplatelet response to clopidogrel but maintain their response to ticlopidine, suggesting ticlopidine is an effective alternative for this genetic subgroup.
May support preferring ticlopidine over clopidogrel in CYP2C19 poor metabolizers; leaves open need for randomized confirmation in CAD.
We examined the influence of CYP2C19 polymorphisms on the antiplatelet effects of clopidogrel and ticlopidine. The platelet aggregation induced by 20 µmol/l adenosine diphosphate (ADP) and CYP2C19 single-nucleotide polymorphisms (*2 and *3) was determined in patients with coronary artery disease (CAD) who were taking aspirin alone (n = 21), aspirin plus clopidogrel (n = 97), or aspirin plus ticlopidine (n = 47). The degree of platelet aggregation in the clopidogrel group, although not in the ticlopidine group, depended on the CYP2C19 polymorphism, and the maximal platelet aggregation in poor metabolizers (PMs) taking clopidogrel was equivalent to that in the group taking aspirin alone. After being switched from clopidogrel to ticlopidine, all seven of the PMs showed markedly lower platelet aggregation. These results suggest that CYP2C19 polymorphisms have a profound impact on the antiplatelet effect of clopidogrel but not on that of ticlopidine. Ticlopidine may be an effective therapeutic option for CYP2C19 PMs.
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Maeda et al. (2010) conducted an observational in Coronary artery disease (CAD) (n=165). Clopidogrel vs Ticlopidine stratified by CYP2C19 polymorphisms vs. Aspirin alone was evaluated on Platelet aggregation induced by 20 µmol/l adenosine diphosphate (ADP). CYP2C19 polymorphisms significantly reduced the antiplatelet effect of clopidogrel, but not ticlopidine, with poor metabolizers on clopidogrel showing aggregation equivalent to aspirin alone.
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