Nghiên cứu ứng dụng tính đa hình gen đột biến kháng clopidogrel trong điều trị sau đặt stent động mạch vành

Impact of CYP2C19 Polymorphism on Platelet Response to Clopidogrel in Vietnamese Patients with Percutaneous Coronary Intervention Nguyễn Đoàn Thủy Bùi Đình Tùng, Nguyễn Thị Ngọ

Impact of CYP2C19 Polymorphism

on Platelet Response to Clopidogrel

in Vietnamese Patients with Percutaneous Coronary Intervention

Nguyễn Đoàn Thủy Bùi Đình Tùng, Nguyễn Thị Ngọc Hồng

Hanoi Medical University

• 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

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 (1 st 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

(2 nd time)

Poor metabolizers

Carriers of 2 LoF alleles

(n=1)

Ticagrelor (90mg bid)

in 30 days

Platelet function testing

(2 nd time)

STATISTICAL ANALYSIS

Performed using Stata11 software

Demographic data

Genotype n %

*1/*1 10 33.3

*1/*3 1 3.3

*2/*2 1 3.3

*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 (1 st 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 (1 st time) IM (2 nd 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 (2 nd 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 (1 st time) PM (2 nd time)

Ristocetin 13 27

Platelet aggregation (%) in 1 PM, before and

30 days after taking Ticagrelor

• 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!