TY  - CONF
AU  - Backović, D.
AU  - Ignjatović, Svetlana
AU  - Rakicević, Ljiljana
AU  - Novković, Mirjana
AU  - Kusić-Tisma, Jelena
AU  - Radojković, Dragica
AU  - Strugarević, Evgenija
AU  - Čalija, Branko
AU  - Radak, Đorđe
AU  - Kovac, M.
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2744
AB  - Background: Carotid endarterectomy (CEA) is the standard treatment
for carotid stenosis. Dual antiplatelet therapy, including aspirin and
clopidogrel, has a potential role in reducing the risk of stroke after car-
otid surgery. However, clopidogrel high on-treatment platelet reactiv-
ity (HTPR) is quite a common phenomenon.
Aims: Our study aimed to evaluate genetic and non-genetic factors as
possible risks for clopidogrel-HTPR in patients with carotid artery
stenosis undergoing CEA.
Methods: Using multiple-electrode impedance aggregometry (MEA)
the antiplatelet effectiveness of clopidogrel was prospectively evaluated
in 112 patients (66.2   8.1 years). Measurements were made after 24 h,
7 and 30 days of clopidogrel treatment, which was introduced after
elective CEA at a dose of 75 mg daily, for at least 30 days. Clopido-
grel-HTPR was defined as an adenosine diphosphate (ADP) - throm-
bin receptor activating peptide (TRAP) platelet aggregation ratio ≥
52%. CYP2C19*2 genotyping was performed by TaqMan assay.
Logistic regression models were used to estimate predictors for low
responsiveness. The Ethics Committee of the “Dedinje” Institute for
Cardiovascular Diseases approved the research protocol. All patients
gave written informed consent prior to study inclusion.
Results: According to this specific cut-off value for our population, the
number of patients with HTPR declined from 79.5% 24 h after intro-
ducing clopidogrel to 25% after 30 days of treatment. Analysis showed
that 16/30 patients carrying the CYP2C19*2 gene variant had HTPR,
in contrast to 12/82 non-carriers of this allele (P< 0.001). Multivariate
logistic regression analysis identified the CYP2C19*2 gene variant
(OR 4.384, 95% CI 1.296-14.833, P=0.017) and high total cholesterol
(OR 2.090, 95% CI 1.263-3.459, P=0.004) as the only independent risk
factors for clopidogrel-HTPR.
Conclusions: The CYP2C19*2 gene variant and high total cholesterol
level were risk factors for clopidogrel-HTPR in patients with carotid
artery stenosis undergoing CEA.
PB  - Elsevier
C3  - Journal of Thrombosis and Haemostasis
T1  - Risk factors for clopidogrel high on-treatment platelet reactivity in patients with carotid artery stenosis undergoing endarterectomy
VL  - 14
IS  - S1
SP  - 110
EP  - 110
DO  - 10.1111/jth.13325
ER  - 

@conference{
author = "Backović, D. and Ignjatović, Svetlana and Rakicević, Ljiljana and Novković, Mirjana and Kusić-Tisma, Jelena and Radojković, Dragica and Strugarević, Evgenija and Čalija, Branko and Radak, Đorđe and Kovac, M.",
year = "2016",
abstract = "Background: Carotid endarterectomy (CEA) is the standard treatment
for carotid stenosis. Dual antiplatelet therapy, including aspirin and
clopidogrel, has a potential role in reducing the risk of stroke after car-
otid surgery. However, clopidogrel high on-treatment platelet reactiv-
ity (HTPR) is quite a common phenomenon.
Aims: Our study aimed to evaluate genetic and non-genetic factors as
possible risks for clopidogrel-HTPR in patients with carotid artery
stenosis undergoing CEA.
Methods: Using multiple-electrode impedance aggregometry (MEA)
the antiplatelet effectiveness of clopidogrel was prospectively evaluated
in 112 patients (66.2   8.1 years). Measurements were made after 24 h,
7 and 30 days of clopidogrel treatment, which was introduced after
elective CEA at a dose of 75 mg daily, for at least 30 days. Clopido-
grel-HTPR was defined as an adenosine diphosphate (ADP) - throm-
bin receptor activating peptide (TRAP) platelet aggregation ratio ≥
52%. CYP2C19*2 genotyping was performed by TaqMan assay.
Logistic regression models were used to estimate predictors for low
responsiveness. The Ethics Committee of the “Dedinje” Institute for
Cardiovascular Diseases approved the research protocol. All patients
gave written informed consent prior to study inclusion.
Results: According to this specific cut-off value for our population, the
number of patients with HTPR declined from 79.5% 24 h after intro-
ducing clopidogrel to 25% after 30 days of treatment. Analysis showed
that 16/30 patients carrying the CYP2C19*2 gene variant had HTPR,
in contrast to 12/82 non-carriers of this allele (P< 0.001). Multivariate
logistic regression analysis identified the CYP2C19*2 gene variant
(OR 4.384, 95% CI 1.296-14.833, P=0.017) and high total cholesterol
(OR 2.090, 95% CI 1.263-3.459, P=0.004) as the only independent risk
factors for clopidogrel-HTPR.
Conclusions: The CYP2C19*2 gene variant and high total cholesterol
level were risk factors for clopidogrel-HTPR in patients with carotid
artery stenosis undergoing CEA.",
publisher = "Elsevier",
journal = "Journal of Thrombosis and Haemostasis",
title = "Risk factors for clopidogrel high on-treatment platelet reactivity in patients with carotid artery stenosis undergoing endarterectomy",
volume = "14",
number = "S1",
pages = "110-110",
doi = "10.1111/jth.13325"
}

Backović, D., Ignjatović, S., Rakicević, L., Novković, M., Kusić-Tisma, J., Radojković, D., Strugarević, E., Čalija, B., Radak, Đ.,& Kovac, M.. (2016). Risk factors for clopidogrel high on-treatment platelet reactivity in patients with carotid artery stenosis undergoing endarterectomy. in Journal of Thrombosis and Haemostasis
Elsevier., 14(S1), 110-110.
https://doi.org/10.1111/jth.13325

Backović D, Ignjatović S, Rakicević L, Novković M, Kusić-Tisma J, Radojković D, Strugarević E, Čalija B, Radak Đ, Kovac M. Risk factors for clopidogrel high on-treatment platelet reactivity in patients with carotid artery stenosis undergoing endarterectomy. in Journal of Thrombosis and Haemostasis. 2016;14(S1):110-110.
doi:10.1111/jth.13325 .

Backović, D., Ignjatović, Svetlana, Rakicević, Ljiljana, Novković, Mirjana, Kusić-Tisma, Jelena, Radojković, Dragica, Strugarević, Evgenija, Čalija, Branko, Radak, Đorđe, Kovac, M., "Risk factors for clopidogrel high on-treatment platelet reactivity in patients with carotid artery stenosis undergoing endarterectomy" in Journal of Thrombosis and Haemostasis, 14, no. S1 (2016):110-110,
https://doi.org/10.1111/jth.13325 . .