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Stage-dependent differential effects of interleukin-1 isoforms on experimental atherosclerosis Comparison of inhospital mortality, length of hospitalization, costs, and vascular complications of percutaneous coronary interventions guided by ultrasound versus angiography The Role of the Pericardium in Heart Failure: Implications for Pathophysiology and Treatment The impact of intravascular ultrasound guidance during drug eluting stent implantation on angiographic outcomes Colchicine Reduces Cardiovascular Events in Chronic Coronary Disease Clinical impact of PCSK9 inhibitor on stabilization and regression of lipid-rich coronary plaques: a near-infrared spectroscopy study Accuracy of Fractional Flow Reserve Derived From Coronary Angiography Prognostic value of coronary artery calcium screening in subjects with and without diabetes The Evolution of β-Blockers in Coronary Artery Disease and Heart Failure (Part 1/5) Relation between baseline plaque features and subsequent coronary artery remodeling determined by optical coherence tomography and intravascular ultrasound
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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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