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TAVI Represents an Anti-Inflammatory Therapy via Reduction of Shear Stress Induced, Piezo-1-Mediated Monocyte Activation Treatment Effects of Pulmonary Artery Denervation for Pulmonary Arterial Hypertension Stratified by REVEAL Risk Score: Results from PADN-CFDA Trial Hemodynamic, Functional, and Clinical Responses to Pulmonary Artery Denervation in Patients With Pulmonary Arterial Hypertension of Different Causes 3-Year Outcomes After 2-Stent With Provisional Stenting for Complex Bifurcation Lesions Defined by DEFINITION Criteria Clinical Impact of Residual Leaks Following Left Atrial Appendage Occlusion: Insights From the NCDR LAAO Registry Half-Dose Direct Oral Anticoagulation Versus Standard Antithrombotic Therapy After Left Atrial Appendage Occlusion Haemodynamic definitions and updated clinical classification of pulmonary hypertension A Score to Assess Mortality After Percutaneous Mitral Valve Repair Propensity-Matched 1-Year Outcomes Following Transcatheter Aortic Valve Replacement in Low-Risk Bicuspid and Tricuspid Patients Defining cardiovascular toxicities of cancer therapies: an International Cardio-Oncology Society (IC-OS) consensus statement
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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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