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Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents Update in the Percutaneous Management of Coronary Chronic Total Occlusions Comparison of Stenting Versus Bypass Surgery According to the Completeness of Revascularization in Severe Coronary Artery Disease: Patient-Level Pooled Analysis of the SYNTAX, PRECOMBAT, and BEST Trials Percutaneous Coronary Intervention Readmissions Where Are the Solutions? High-Sensitivity Troponin I Levels and Coronary Artery Disease Severity, Progression, and Long-Term Outcomes Reappraisal of Reported Genes for Sudden Arrhythmic Death: An Evidence-Based Evaluation of Gene Validity for Brugada Syndrome Risk Stratification Guided by the Index of Microcirculatory Resistance and Left Ventricular End-Diastolic Pressure in Acute Myocardial Infarction Selection of stenting approach for coronary bifurcation lesions Coronary Artery Calcium Progression Is Associated With Coronary Plaque Volume Progression - Results From a Quantitative Semiautomated Coronary Artery Plaque Analysis Myocardial Inflammation Predicts Remodeling and Neuroinflammation After Myocardial Infarction
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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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