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Long-Term Outcomes of Anticoagulation for Bioprosthetic Valve Thrombosis Aliskiren, Enalapril, or Aliskiren and Enalapril in Heart Failure Clinical Risk Factors and Atherosclerotic Plaque Extent to Define Risk for Major Events in Patients Without Obstructive Coronary Artery Disease: The Long-Term Coronary Computed Tomography Angiography CONFIRM Registry Permanent pacemaker use among patients with heart failure and preserved ejection fraction: Findings from the Acute Decompensated Heart Failure National Registry (ADHERE) National Registry Comparison of safety and periprocedural complications of transfemoral aortic valve replacement under local anaesthesia: minimalist versus complete Heart Team Sleep quality and risk of coronary heart disease-a prospective cohort study from the English longitudinal study of ageing Safety and efficacy of a self-expanding versus a balloon-expandable bioprosthesis for transcatheter aortic valve replacement in patients with symptomatic severe aortic stenosis: a randomised non-inferiority trial Heart Failure With Improved Ejection Fraction-Is it Possible to Escape One’s Past? Frailty and Bleeding in Older Adults Undergoing TAVR or SAVR: Insights From the FRAILTY-AVR Study Coronary plaque redistribution after stent implantation is determined by lipid composition: A NIRS-IVUS analysis
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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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