Ticagrelor demonstrated superior pharmacodynamic effects with lower platelet reactivity compared to clopidogrel irrespective of CYP2C19 genotype or metabolizer status (P<0.01).
Observational (n=174)
Does ticagrelor improve platelet inhibition compared to clopidogrel irrespective of CYP2C19 genotype in patients with coronary artery disease?
Ticagrelor provides superior and more consistent platelet inhibition compared to clopidogrel, overcoming the reduced antiplatelet effect seen with clopidogrel in patients carrying CYP2C19 loss-of-function alleles.
p-value: p=<0.01
BACKGROUND: The influence of cytochrome P450 (CYP) 2C19 genotype on platelet function in patients treated with ticagrelor versus clopidogrel is unknown. METHODS AND RESULTS: CYP2C19 (*1, *2, *3, *4, *5, *6, *7, *8, *17) genotyping was performed in patients with coronary artery disease treated with ticagrelor (180-mg load, 90 mg BID) (n=92) or clopidogrel (600-mg load, 75 mg/d) (n=82). All patients received 75 to 100 mg/d aspirin. Platelet function was measured by aggregometry, VerifyNow P2Y12 assay, and vasodilator-stimulated phosphoprotein-phosphorylation assay at predose, 8 hours postloading, and maintenance. In each treatment group, patients were categorized according to 2C19 genotype carrier status (loss-of-function, gain-of-function) and metabolizer status. Kruskal-Wallis test was used to compare platelet function among these categories for each treatment, and Wilcoxon rank sum test was used to compare platelet function between the clopidogrel and ticagrelor groups for each category. There was no statistically significant influence of genotype on platelet function during aspirin therapy alone. Ticagrelor exhibited lower platelet reactivity than clopidogrel by all assays irrespective of 2C19 genotype or metabolizer status (P<0.01). Loss-of-function carriers had greater platelet reactivity during clopidogrel therapy. The influence of genotype on platelet reactivity was greatest during clopidogrel maintenance and best demonstrated by the VerifyNow P2Y12 assay. CONCLUSIONS: This report is the first to demonstrate the superior pharmacodynamic effect of ticagrelor compared with clopidogrel irrespective of CYP2C19 genotype. Whereas CYP2C19 genotype influenced the antiplatelet effect of clopidogrel, there was no effect of CYP2C19 genotype during ticagrelor therapy.
Tantry et al. (Tue,) conducted a observational in Coronary artery disease (n=174). Ticagrelor vs. Clopidogrel (600-mg load, 75 mg/d) was evaluated on Platelet function measured by aggregometry, VerifyNow P2Y12 assay, and VASP assay (p=<0.01). Ticagrelor demonstrated superior pharmacodynamic effects with lower platelet reactivity compared to clopidogrel irrespective of CYP2C19 genotype or metabolizer status (P<0.01).