Article

The pharmacogenetics and pharmacodynamics of clopidogrel response: an analysis from the PRINC (Plavix Response in Coronary Intervention) trial.

Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand.
01/2009; 1(6):620-7. DOI:10.1016/j.jcin.2008.09.008 pp.620-7
Source: PubMed

ABSTRACT This study assessed the effect of pharmacogenetics on the antiplatelet effect of clopidogrel.
Variability in clopidogrel response might be influenced by polymorphisms in genes coding for drug metabolism enzymes (cytochrome P450 [CYP] family), transport proteins (P-glycoprotein) and/or target proteins for the drug (adenosine diphosphate-receptor P2Y12).
Sixty patients undergoing elective percutaneous coronary intervention in the randomized PRINC (Plavix Response in Coronary Intervention) trial had platelet function measured using the VerifyNow P2Y12 analyzer after a 600-mg or split 1,200-mg loading dose and after a 75- or 150-mg daily maintenance dosage. Polymerase chain reaction-based genotyping evaluated polymorphisms in the CYP2C19, CYP2C9, CYP3A4, CYP3A5, ABCB1, P2Y12, and CES genes.
CYP2C19*1*1 carriers had greater platelet inhibition 2 h after a 600-mg dose (median: 23%, range: 0% to 66%), compared with platelet inhibition in CYP2C19*2 or *4 carriers (10%, 0% to 56%, p = 0.029) and CYP2C19*17 carriers (9%, 0% to 98%, p = 0.026). CYP2C19*2 or *4 carriers had greater platelet inhibition with the higher loading dose than with the lower dose at 4 h (37%, 8% to 87% vs. 14%, 0% to 22%, p = 0.002) and responded better with the higher maintenance dose regimen (51%, 15% to 86% vs. 14%, 0% to 67%, p = 0.042).
Carriers of the CYP2C19*2 and *4 alleles showed reduced platelet inhibition after a clopidogrel 600-mg loading dose but responded to higher loading and maintenance dose regimens. Genotyping for the relevant gene polymorphisms may help to individualize and optimize clopidogrel treatment. (Australia New Zealand Clinical Trials Registry; ACTRN12606000129583).

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Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

*4 carriers
 
adenosine diphosphate-receptor P2Y12
 
CES genes
 
clopidogrel 600-mg loading dose
 
Coronary Intervention
 
cytochrome P450 [CYP] family
 
drug metabolism enzymes
 
higher loading
 
higher loading dose
 
higher maintenance dose regimen
 
maintenance dose regimens
 
optimize clopidogrel treatment
 
patients undergoing elective percutaneous coronary intervention
 
platelet inhibition
 
randomized PRINC
 
relevant gene polymorphisms
 
split 1,200-mg loading dose
 
target proteins
 
transport proteins
 
VerifyNow P2Y12 analyzer