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Pre-procedural platelet reactivity after clopidogrel loading in korean patients undergoing scheduled percutaneous
Min-Kyung Kang1, Young-Hoon Jeong, Seong-Eun Yoon
1Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea.
Insights
Korean patients often have high post-clopidogrel platelet reactivity (HPPR) due to CYP2C19 variant alleles. A standard loading dose of clopidogrel is insufficient for adequate platelet inhibition in these patients.
Area of Science:
- Pharmacogenomics
- Cardiovascular Medicine
- Clinical Pharmacology
Background:
- CYP2C19 variant alleles (*2 and *3) are more prevalent in Korean populations, potentially affecting antiplatelet drug efficacy.
- Pre-procedural platelet reactivity (PR) can influence outcomes in patients undergoing percutaneous coronary intervention (PCI).
Purpose of the Study:
- To investigate the level of PR and the prevalence of high post-clopidogrel platelet reactivity (HPPR) in Korean patients receiving a standard loading dose (LD) of clopidogrel.
- To assess the impact of CYP2C19 genotype on PR and HPPR in this patient cohort.
Main Methods:
- 215 Korean patients undergoing scheduled PCI had their PR assessed 12-24 hours after a 300-mg clopidogrel LD.
- Platelet reactivity was measured using conventional aggregometry and VerifyNow, with HPPR defined as >50% maximal PR at 5 µmol/L ADP.
- CYP2C19 genotyping was performed on 176 patients.
Main Results:
- The prevalence of HPPR was 52.1% based on ADP-induced maximal PR >50% at 5 µmol/L.
- High P2Y₁₂ reaction units (PRU ≥240) were observed in 69.8% of patients.
- Carriage of CYP2C19 variant alleles (*2 or *3) was a significant predictor of HPPR (OR 4.202, p<0.001).
Conclusions:
- A 300-mg loading dose of clopidogrel does not achieve adequate pre-procedural platelet inhibition in Korean patients undergoing scheduled PCI.
- The higher prevalence of CYP2C19 mutant alleles in Korean patients is associated with increased HPPR.
- These findings suggest potential genotype-guided antiplatelet therapy strategies may be warranted.
Aim:
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.
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