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The Use of Sex-Specific Factors in the Assessment of Women’s Cardiovascular Risk Exercise Intolerance in Patients With Heart Failure: JACC State-of-the-Art Review ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography in global cardiovascular risk assessment and in evaluation of patients with chest pain: a report of the American College of Cardiology Foundation Clinical Expert Consensus Task Force (ACCF/AHA Writing Committee to Update the 2000 Expert Consensus Document on Electron Beam Computed Tomography) developed in collaboration with the Society of Atherosclerosis Imaging and Prevention and the Society of Cardiovascular Computed Tomography Longitudinal Change in Galectin-3 and Incident Cardiovascular Outcomes Meta-Analysis of Effectiveness and Safety of Transcatheter Aortic Valve Implantation Versus Surgical Aortic Valve Replacement in Low-to-Intermediate Surgical Risk Cohort Impact of Intravascular Ultrasound-Guided Drug-Eluting Stent Implantation on Patients With Chronic Kidney Disease: Subgroup Analysis From ULTIMATE Trial Comparison of the Efficacy and Safety Outcomes of Edoxaban in 8040 Women Versus 13 065 Men With Atrial Fibrillation in the ENGAGE AF-TIMI 48 Trial Association of Smoking Status With Long‐Term Mortality and Health Status After Transcatheter Aortic Valve Replacement: Insights From the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry Lifestyle Modifications for Preventing and Treating Heart Failure 2019 Guidelines on Diabetes, Pre-Diabetes and Cardiovascular Diseases developed in collaboration with the EASD ESC Clinical Practice Guidelines
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Review Article12 (4), e007811

JOURNAL：Circulation. Article Link

Clopidogrel Pharmacogenetics: State-of-the-Art Review and the TAILOR-PCI Study

NL Pereira, CS Rihal, DYF So et al. Keywords: clinical trial; clopidogrel; cytochrome P450 CYP2C19; drug labeling; genetics; humans; pharmacogenetics

ABSTRACT

Common genetic variation in CYP2C19 (cytochrome P450, family 2, subfamily C, polypeptide 19) *2 and *3 alleles leads to a loss of functional protein, and carriers of these loss-of-function alleles when treated with clopidogrel have significantly reduced clopidogrel active metabolite levels and high on-treatment platelet reactivity resulting in increased risk of major adverse cardiovascular events, especially after percutaneous coronary intervention. The Food and Drug Administration has issued a black box warning advising practitioners to consider alternative treatment in CYP2C19 poor metabolizers who might receive clopidogrel and to identify such patients by genotyping. However, routine clinical use of genotyping for CYP2C19 loss-of-function alleles in patients undergoing percutaneous coronary intervention is not recommended by clinical guidelines because of lack of prospective evidence. To address this critical gap, TAILOR-PCI (Tailored Antiplatelet Initiation to Lessen Outcomes due to Decreased Clopidogrel Response After Percutaneous Coronary Intervention) is a large, pragmatic, randomized trial comparing point-of-care genotype-guided antiplatelet therapy with routine care to determine whether identifying CYP2C19 loss-of-function allele patients prospectively and prescribing alternative antiplatelet therapy is beneficial.

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