Pre-procedural platelet reactivity after clopidogrel loading in korean patients undergoing scheduled percutaneous coronary intervention.
OBJECTIVE
Pre-procedural platelet reactivity (PR) in Korean patients may be greater because the CYP2C19*2 and *3 variant alleles are more common in Korean patients than in Caucasians. We investigated the level of PR and the prevalence of high post-clopidogrel platelet reactivity (HPPR) after a routine loading dose (LD) of clopidogrel in Korean patients.


METHODS
We assessed the PR level at 12 to 24 hours after a 300-mg LD of clopidogrel in 215 patients undergoing scheduled percutaneous coronary intervention (PCI) (available CYP2C19 genotyping: n =176). PR was measured by conventional aggregometry and VerifyNow. Based on a previous study, HPPR was defined as a 5 µmol/L ADP-induced maximal PR >50%.


RESULTS
With 5 and 20 µmol/L ADP stimuli, maximal PR were 48.7 ± 17.1% and 62.1 ± 15.7%, respectively, and the prevalence of HPPR reached 52.1%. The highest quartile cut-offs of 5 and 20 µmol/L ADP-induced PR(max) were 64% and 75%, respectively. P2Y₁₂ reaction unit (PRU) was 274 ± 76, and 69.8% (n =150) showed PRU ≥240. A carrier of at least one CYP2C19 variant allele showed higher PRs than non-carriers. In multivariate regression analysis, carriage of the CYP2C19 variant allele (*2 or *3) was determined to be a significant predictor of HPPR (odds ratio 4.202, 95% confidence interval 1.996 to 8.850, p< 0.001).


CONCLUSIONS
Korean patients undergoing scheduled PCI cannot achieve adequate pre-procedural platelet inhibition from a 300-mg LD of clopidogrel, which is related with a higher prevalence of the CYP2C19 mutant allele.
Kang
Min-Kyung
MK
Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea.
Jeong
Young-Hoon
YH
Yoon
Seong-Eun
SE
Koh
Jin-Sin
JS
Kim
In-Suk
IS
Park
Yongwhi
Y
Hwang
Seok-Jae
SJ
Kwak
Choong Hwan
CH
Hwang
Jin-Yong
JY
D054058:Acute Coronary Syndrome / Q000235:genetics / Q000628:therapy*; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D011110:Polymorphism, Genetic / Q000235:genetics; D056910:Republic of Korea; D012307:Risk Factors; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine