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Circulating sST2 and catestatin levels in patients with acute worsening of heart failure: a report from the CATSTAT-HF study Cardiovascular biomarkers in patients with acute decompensated heart failure randomized to sacubitril-valsartan or enalapril in the PIONEER-HF trial Stopping or continuing clopidogrel 12 months after drug-eluting stent placement: the OPTIDUAL randomized trial Late kidney injury after transcatheter aortic valve replacement Association of Prior Left Ventricular Ejection Fraction With Clinical Outcomes in Patients With Heart Failure With Midrange Ejection Fraction Myocardial bridging: contemporary understanding of pathophysiology with implications for diagnostic and therapeutic strategies Percutaneous coronary intervention versus coronary artery bypass grafting in patients with three-vessel or left main coronary artery disease: 10-year follow-up of the multicentre randomised controlled SYNTAX trial Timing of intervention in asymptomatic patients with valvular heart disease Impact of the Use of Intravascular Imaging on Patients Who Underwent Orbital Atherectomy Myofibroblast Phenotype and Reversibility of Fibrosis in Patients With End-Stage Heart Failure
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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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