Abstract 20393: First Analysis of Relation Between CYP2C19 Genotype and Platelet Function in Ticagrelor versus Clopidogrel Treated Patients: Results from the ONSET/OFFSET and RESPOND Studies
Background: CYP2C19 genotype influences platelet aggregation (PA) and clinical outcomes in patients treated with clopidogrel (C), however its relation to platelet function in ticagrelor (T) treated pts is unknown.
Methods: CYP2C19 (*1,*2,* 3, *4, *5, *6, *7,*8,*17) genotyping was performed in CAD pts treated with T (180mg load, 90mg bid MD [n=92]), and C (600mg load, 75mg qd MD [n=82]). All patients received 75-100mg qd aspirin. Platelet function was measured by aggregometry, VerifyNow P2Y12 assay and VASP-phosphorylation assay at pre-dose, 8 h post- loading and during maintenance. In each treatment group, pts. were categorized according to 2C19 genotype-carrier status [loss-of-function (LOF), gain-of-function (GOF)]; metabolizer status [ultra (UM), extensive (EM), intermediate (IM) and poor (PM)]; Kruskal-Wallis test was used to compare platelet function within the above categories for each treatment and Wilcoxon rank-sum test was used to compare platelet function between clopidogrel and ticagrelor groups for each category.
Results: The frequencies of categories were: UM=32%, EM=34%, IM=32%, PM=3%, LOF=35%, GOF=32%, T/T=23%, T/C=48%, and C/C=29%. There was no effect of genotype on PA during aspirin therapy alone. T exhibited higher platelet inhibition than C that was consistent across assays irrespective of 2C19 SNP carrier or metabolizer status (p<0.01). The effect of genotype on C-induced platelet inhibition was more evident during MD compared to post-loading and most effectively demonstrated by the VerifyNow P2Y12 assay (Table).
Conclusion: Compared to C, T is associated with superior and consistent platelet inhibition irrespective of genotype. This is the first report to demonstrate the absence of an effect of CYP2C19 genotype on the antiplatelet effects of T, although CYP2C19 did influence the antiplatelet effects of C.
- © 2010 by American Heart Association, Inc.