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Positive clinical response to clopidogrel is independent of paraoxonase 1 Q192R and CYP2C19 genetic variants
Author(s) -
MartínezQuintana Efrén,
MedinaGil José M,
RodríguezGonzález Fayna,
GaraySánchez Paloma,
Limiñana José M,
Saavedra Pedro,
Tugores Antonio
Publication year - 2014
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.275
Subject(s) - cyp2c19 , clopidogrel , pon1 , medicine , omeprazole , paraoxonase , concomitant , aspirin , proton pump inhibitor , cardiology , ticlopidine , gastroenterology , rabeprazole , pharmacology , cytochrome p450 , biology , oxidative stress , metabolism , genotype , gene , biochemistry
Abstract There is increasing controversy about the influence of serum paraoxonase type 1 and cytochrome CYP2C19 in the conversion of clopidogrel to its pharmaceutically active metabolite. The effect of concomitant medication with the proton pump inhibitor omeprazole has been also subject of intense scrutiny. We present a cohort of 263 patients receiving anti‐platelet aggregation treatment with clopidogrel and aspirin for 1 year. The paraoxonase 1 gene Q192R variant along with the presence of CYP2C19*2 and *3 loss of function alleles, concomitant medication with proton pump inhibitors and known cardiovascular risk factors were examined to determine their influence in disease relapse due to an ischaemic event during the 12 month treatment period. The low number of patients suffering a relapse (20 out of 263), indicates that double anti‐aggregation therapy with aspirin and clopidogrel was very effective in our patients. Among the relapsers, evidence of coronary heart disease was the most influencial factor affecting response to therapy, while the presence of the paraoxonase 1 Q192R variant, loss of function of CYP2C19, and concomitant medication with omeprazole were non‐significant.