The Personalization Of Clopidogrel Antiplatelet Therapy In Coronary Artery Disease Patients Using Pharmacometabonomics, Pharmacogenetics And Platelets Function Testing
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Date
2016-09
Authors
Mostafa, Arwa Mohamed Amin
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Abstract
Clopidogrel is a substantial antiplatelet drug. Some patients on clopidogrel
treatment suffer from high on treatment platelets reactivity (HTPR) which may lead to
poor outcome. Genotyping of CYP2C19 had been recommended to predict clopidogrel
response. However, this might be insufficient to predict the response.
Pharmacometbonomics analysis using nuclear magnetic resonance (1H-NMR)
spectroscopy can help to identify novel biomarkers of HTPR in plasma and urine. The
primary aim of this project was to evaluate the use of pharmacometabonomics,
pharmacogenetics and platelets function testing for the personalization of clopidogrel
anti-platelet therapy in coronary artery disease patients. Secondary objectives included
determining the frequency of CYP2C19 *2 and *3 polymorphisms and the frequency
of clopidogrel HTPR. Moreover, this study aimed to evaluate the effect of CYP2C19
polymorphisms and other non-genetic factors on clopidogrel response. A total of 89
CAD patients planned for interventional angiographic procedure (IAP) were recruited
and genotyped for CYP2C19*2 and *3. Out of those, 71 patients were loaded with
clopidogrel 600 mg. Blood and urine samples were collected from patients before
loading and 6 hours after loading for the pharmacometabonomics analysis. Patients
were assessed for platelets function testing (PFT) using the VerifyNow-P2Y12 kit at
6 hours after loading. Multivariate analysis was used to find the discriminating
metabolites. Out of the 89 recruited patients, 38 (42.7%) and 15 (16.9%) were carriersClopidogrel is a substantial antiplatelet drug. Some patients on clopidogrel
treatment suffer from high on treatment platelets reactivity (HTPR) which may lead to
poor outcome. Genotyping of CYP2C19 had been recommended to predict clopidogrel
response. However, this might be insufficient to predict the response.
Pharmacometbonomics analysis using nuclear magnetic resonance (1H-NMR)
spectroscopy can help to identify novel biomarkers of HTPR in plasma and urine. The
primary aim of this project was to evaluate the use of pharmacometabonomics,
pharmacogenetics and platelets function testing for the personalization of clopidogrel
anti-platelet therapy in coronary artery disease patients. Secondary objectives included
determining the frequency of CYP2C19 *2 and *3 polymorphisms and the frequency
of clopidogrel HTPR. Moreover, this study aimed to evaluate the effect of CYP2C19
polymorphisms and other non-genetic factors on clopidogrel response. A total of 89
CAD patients planned for interventional angiographic procedure (IAP) were recruited
and genotyped for CYP2C19*2 and *3. Out of those, 71 patients were loaded with
clopidogrel 600 mg. Blood and urine samples were collected from patients before
loading and 6 hours after loading for the pharmacometabonomics analysis. Patients
were assessed for platelets function testing (PFT) using the VerifyNow-P2Y12 kit at
6 hours after loading. Multivariate analysis was used to find the discriminating
metabolites. Out of the 89 recruited patients, 38 (42.7%) and 15 (16.9%) were carriers
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Keywords
The use of pharmacometabonomics, pharmacogenetics and platelets function testing for the personalization , of clopidogrel anti-platelet therapy in coronary artery disease patients