Impact of CYP2C19 polymorphism on platelet response to clopidogrel in Vietnamese patients with percutaneous coronary intervention - Nguyễn Đoàn Thủy

Impact of CYP2C19 Polymorphism 
on Platelet Response to Clopidogrel 
in Vietnamese Patients with 
Percutaneous Coronary Intervention 
Nguyễn Đoàn Thủy 
 Bùi Đình Tùng, Nguyễn Thi ̣ Ngọc Hồng 
Hanoi Medical University 
BACKGROUND 
• Clopidogrel is one of the most widely used 
P2Y12 inhibitors in conjunction with aspirin 
for patients with PCI to prevent stent 
thrombosis. 
• There is significant interindividual variability 
in clopidogrel responsiveness. 
 Metabolism of Clopidogrel 
Polymorphisms of CYP genes and other genes affecting 
metabolism of Clopidogrel 
BACKGROUND 
Carriers of loss-of-function (LoF) CYP2C19 
alleles are at higher risk of stent thrombosis 
and other cardiovascular events. 
OBJECTIVE 
Evaluate the influence of CYP2C19 
polymorphisms on platelet response to 
clopidogrel in patients with PCI 
STUDY SUBJECTS 
• Outpatients undergoing PCI in Vietnam 
National Heart Institute, Bach Mai Hospital. 
• Had received clopidogrel (75mg/d) and 
aspirin (81 mg/d) for at least 1 month 
prior to the study. 
Patient selection 
(n=30) 
Complete blood count testing 
Platelet funtion testing (1st time) 
CYP2C19 genotyping 
Extensive metabolizers 
Noncarriers 
(n=10) 
Continue with current 
clopidogrel dose (75mg/d) 
Intermediate metabolizers 
Carriers of 1 LoF allele 
(n=19) 
Higher dose of clopidogrel 
(225mg/d) in 30 days 
Platelet function testing 
(2nd time) 
Poor metabolizers 
Carriers of 2 LoF alleles 
(n=1) 
Ticagrelor (90mg bid) 
in 30 days 
Platelet function testing 
(2nd time) 
STATISTICAL ANALYSIS 
Performed using Stata11 software 
Demographic data 
Genotype n % 
*1/*1 10 33.3 
*1/*2 18 60.0 
*1/*3 1 3.3 
*2/*2 1 3.3 
Allele n % 
*1 39 65.0 
*2 20 33.3 
*3 1 1.7 
 CYP2C19 genotype and allele frequency 
Association between Status as a Carrier of a CYP2C19 LoF Allele 
and the Primary Efficacy Outcome (death from cardiovascular 
causes, myocardial infarction, or stroke) 
in 1459 subjects in TRITON-TIMI 38 study 
Mega et al., New England Journal of Medicine 2009 
Association between Status as a Carrier of a CYP2C19 LoF Allele 
and Stent Thrombosis in 1459 subjects in TRITON-TIMI 38 study 
Mega et al., New England Journal of Medicine 2009 
Agonists IM (1st time) EM P 
ADP 33.5 ± 8.7 19.2 ± 13.6 0.03 
Ristocetin 58.75 ± 21.27 51.5 ± 28.19 0.21 
Comparison of platelet aggregation (%) 
between IM, before increasing dose of Clopidogrel and EM 
Agonists IM (1st time) IM (2nd time) P 
ADP 33.5 ± 8.7 19.5 ± 5.9 0.01 
Ristocetin 58.75 ± 21.27 60.25 ± 38.03 0.53 
Comparison of platelet aggregation (%) in IM 
before and 30 days after increasing dose of Clopidogrel 
Agonists IM (2nd time) EM P 
ADP 19.5 ± 5.9 19.2 ± 13.6 0.81 
Ristocetin 60.25 ± 38.03 51.5 ± 28.19 0.54 
 Comparison of platelet aggregation (%) between IM, 
30 days after increasing dose of Clopidogrel and EM 
Agonists PM (1st time) PM (2nd time) 
ADP 52 6 
Ristocetin 13 27 
Platelet aggregation (%) in 1 PM, before and 
30 days after taking Ticagrelor 
CONCLUSION 
• CYP2C19 genotype might be a significant 
contributor to the variability in the platelet 
response to clopidogrel therapy in 
Vietnamese patients with PCI. 
TAKE-HOME MESSAGE 
• Application of CYP2C19 genotype to treatment: 
– Clopidogrel 75mg/d for Extensive metabolizers 
– Higher dose of Clopidogrel (225mg/d) for 
Intermediate metabolizers 
– Newer drugs, such as Ticagrelor (90mg bid) for 
Poor metabolizers 
THANKS FOR YOUR ATTENTION!