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Chronic thromboembolic pulmonary hypertension Updated clinical classification of pulmonary hypertension Elaborately Engineering a Self-Indicating Dual-Drug Nanoassembly for Site-Specific Photothermal-Potentiated Thrombus Penetration and Thrombolysis Exercise unmasks distinct pathophysiologic features in heart failure with preserved ejection fraction and pulmonary vascular disease Anatomical Attributes of Clinically Relevant Diagonal Branches in Patients with Left Anterior Descending Coronary Artery Bifurcation Lesions Percutaneous Coronary Intervention Techniques for Bifurcation Disease: Network Meta-analysis Reveals Superiority of Double-Kissing Crush Lesion-Specific and Vessel-Related Determinants of Fractional Flow Reserve Beyond Coronary Artery Stenosis Technical aspects of the culotte technique Anatomical and Functional Computed Tomography for Diagnosing Hemodynamically Significant Coronary Artery Disease: A Meta-Analysis A Randomized Trial Evaluating Online 3-Dimensional Optical Frequency Domain Imaging-Guided Percutaneous Coronary Intervention in Bifurcation Lesions
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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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