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Outcomes with intravascular ultrasound-guided stent implantation: a meta-analysis of randomized trials in the era of drug-eluting stents Circadian Cadence and NR1D1 Tune Cardiovascular Disease Impact of intravascular ultrasound-guided percutaneous coronary intervention on long-term clinical outcomes in a real world population First-in-man evaluation of intravascular optical frequency domain imaging (OFDI) of Terumo: a comparison with intravascular ultrasound and quantitative coronary angiography Role of Proximal Optimization Technique Guided by Intravascular Ultrasound on Stent Expansion, Stent Symmetry Index, and Side-Branch Hemodynamics in Patients With Coronary Bifurcation Lesions Consensus from the 5th European Bifurcation Club meeting Stage B heart failure: management of asymptomatic left ventricular systolic dysfunction Novel percutaneous interventional therapies in heart failure with preserved ejection fraction: an integrative review The spectrum of heart failure: value of left ventricular ejection fraction and its moving trajectories Nuclear Imaging of the Cardiac Sympathetic Nervous System: A Disease-Specific Interpretation in Heart Failure

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.