Genetic Polymorphism Contributing to the Variability of Clopidogrel Response in Patients With Coronary Artery Disease
Study Details
Study Description
Brief Summary
Clopidogrel non-responsiveness is probably multifactorial; several genetic and non genetic factors may contribute to impaired platelet inhibition by clopidogrel. In this regard, it is meaningful to determine genetic polymorphisms contributing to the variability of clopidogrel response in patients with Coronary Artery Therefore, the goal of this study is to determine the impact of the polymorphisms, affecting CYP2C19, ABCB1, ITGB3 and P2RY12 genes, on the response to clopidogrel in patients with CAD.Disease (CAD). In fact, the recognition of these factors might predict the exposure to the risk of thrombosis and cardiovascular death in these patients.
Condition or Disease | Intervention/Treatment | Phase |
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Detailed Description
In an observational study with cross-sectional analysis and prospective data collection, the investigators recruit patients with:
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20 years old
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An established coronary artery disease defined by an episode of ST-elevation myocardial infarction, non-ST-elevation acute coronary syndrome or stable angina
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An exposure to clopidogrel therapy (75 mg per day for at least 10 consecutive days).
The exclusion criteria are:
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Presence of allergy to clopidogrel
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Severe hepatic dysfunction, disease or active pathological bleeding (e.g., gastrointestinal (GI) bleeding)
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Use of glycoprotein IIb/IIIa inhibitors or cilostazol
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inability to give informed consent.
Collected data for patients encompasse baseline characteristics, including age, gender, obesity (defined as a body mass index ≥30 kg/m2), smoking, medical history, and coadministered drugs.
The study protocol was approved by the Ethics Committee for Clinical Research at our center and all subjects gave informed consent for study participation.
Platelet function assay is assessed by the VerifyNow P2Y12 analyzer following manufacturer instructions (Accumetrics, Inc. San Diego, CA, USA) using venous blood samples collected in tube containing 3.2% sodium citrate.
Genotyping for CYP2C19, ABCB1, ITGB3 and P2RY12 polymorphism is performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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non responder Group Platelet function assay: High platelet reactivity: PRU>208 |
Diagnostic Test: Platelet function assay
Platelet function assay
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responder Group Platelet function assay: PRU<208 |
Diagnostic Test: Platelet function assay
Platelet function assay
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Outcome Measures
Primary Outcome Measures
- Platelet reactivity on clopidogrel [at least after 10 days]
Platelet reactivity on clopidogrel is assessed by the VerifyNow P2Y12 assay
Other Outcome Measures
- Genotyping for genetic polymorphisms [an average of 1 month]
Genotyping for genetic polymorphisms is performed using PCR-RFLP and sequencing
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patient >20 years old
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Established coronary artery disease defined by an episode of ST-elevation myocardial infarction, non-ST-elevation acute coronary syndrome or stable angina
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Exposure to clopidogrel therapy (75 mg per day for at least 10 consecutive days).
Exclusion Criteria:
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Presence of allergy to clopidogrel
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Severe hepatic dysfunction
-
Disease or active pathological bleeding (e.g., gastrointestinal (GI) bleeding)
-
Use of glycoprotein IIb/IIIa inhibitors or cilostazol
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inability to give informed consent.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Fattouma Bourguiba Hospital | Monastir | Tunisia | 5000 |
Sponsors and Collaborators
- Hôpital Universitaire Fattouma Bourguiba
Investigators
- Principal Investigator: chouchene saoussen, assistant, Fattouma Bourguiba Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- FattoumaBourguiba