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Adjusted clopidogrel loading dose in carriers of CYP2C19*2 polymorphism reduced platelet reactivity

Bonello L. J Am Coll Cardiol. 2010;doi:10.1016/j.jacc.2010.07.004.

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Non-carriers of the CYP2C19*2 loss-of-function genetic polymorphism were able to overcome high on-treatment platelet reactivity with adjusted loading doses of clopidogrel, new study results indicated.

The study population consisted of 411 patients with non-ST segment elevation acute coronary syndromes undergoing percutaneous coronary intervention. Using the vasodilator-stimulated phosphoprotein (VASP) index, the researchers defined high on-treatment platelet reactivity (HTPR) as a VASP index cutoff value of at least 50%. Using allele-specific polymerase chain reactions, the researchers determined the presence of the CYP2C19*2 genetic polymorphism in the study patients. Those carrying the 2C19*2 genetic polymorphism and showing HTPR after an initial 600-mg loading dose of clopidogrel (Plavix, Sanofi-Aventis) received an adjustment of up to three additional 600-mg loading doses of clopidogrel to obtain a VASP index of less than 50%.

One hundred thirty-four patients carried at least one 2C19*2 loss-of-function allele (11 homozygous and 123 heterozygous); of those, 103 were reported to have HTPR. According to the study results, the mean standard deviation VASP index in the patients carrying the 2C19*2 allele was higher than in homozygous patients for the wild type alleles (61.7 ± 18.4% vs. 49.2 ± 24.2%; P<.001). Carriers of the 2C19*2 allele had a lower prevalence of HTPR vs. patients with the wild-type genotype (77% vs. 55.6%; P<.0001). All 103 patients carrying at least one 2C19*2 allele and who also had HTPR received a second loading dose of clopidogrel, resulting in a reported decrease in VASP index vs. those who did not receive the additional clopidogrel bolus (69.7 ± 10.1% vs. 50.6 ± 17.6%; P<.0001). Dose adjustment according to platelet reactivity monitoring enabled 88% of 2C19*2 carriers who also had HTPR to obtain a VASP index of less than 50%, the researchers reported.

“An increased or tailored clopidogrel loading dose according to plate reactivity monitoring can overcome HTPR in most carriers of CYP2C19*2 loss-of-function polymorphism, which may result in reduced thrombotic risk post-PCI,” the researchers concluded. “The results of the present study suggest that the genetic polymorphism is not required to enable optimal platelet reactivity inhibition to be reached in patients exhibiting HTPR because a dose-adjustment strategy according to platelet reactivity monitoring is efficient regardless of genetic status.”

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