Abstract | BACKGROUND: 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:
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Authors | Udaya S Tantry, Kevin P Bliden, Cheryl Wei, Robert F Storey, Martin Armstrong, Kathleen Butler, Paul A Gurbel |
Journal | Circulation. Cardiovascular genetics
(Circ Cardiovasc Genet)
Vol. 3
Issue 6
Pg. 556-66
(Dec 2010)
ISSN: 1942-3268 [Electronic] United States |
PMID | 21079055
(Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Platelet Aggregation Inhibitors
- Purinergic P2Y Receptor Antagonists
- Clopidogrel
- Aryl Hydrocarbon Hydroxylases
- CYP2C19 protein, human
- Cytochrome P-450 CYP2C19
- Ticagrelor
- Adenosine
- Ticlopidine
- Aspirin
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Topics |
- Adenosine
(administration & dosage, analogs & derivatives, pharmacokinetics)
- Aged
- Aryl Hydrocarbon Hydroxylases
(genetics)
- Aspirin
(therapeutic use)
- Clopidogrel
- Coronary Artery Disease
(drug therapy)
- Cytochrome P-450 CYP2C19
- Double-Blind Method
- Genotype
- Humans
- Male
- Middle Aged
- Pharmacokinetics
- Platelet Aggregation
(drug effects)
- Platelet Aggregation Inhibitors
(pharmacokinetics, therapeutic use)
- Platelet Function Tests
- Purinergic P2Y Receptor Antagonists
- Ticagrelor
- Ticlopidine
(administration & dosage, analogs & derivatives, pharmacokinetics)
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