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Angiotensin–Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction Impact of Intravascular Ultrasound-Guided Percutaneous Coronary Intervention on Long-Term Clinical Outcomes in Patients Undergoing Complex Procedures The year in cardiology: heart failure: The year in cardiology 2019 Baseline Features of the VICTORIA (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction) Trial Prevalence and clinical implications of valvular calcification on coronary computed tomography angiography Operator Experience and Outcomes After Left Main Percutaneous Coronary Intervention Poor Long-Term Survival in Patients With Moderate Aortic Stenosis Rationale and design of the GUIDE-IT study: Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure Minimizing Permanent Pacemaker Following Repositionable Self-Expanding Transcatheter Aortic Valve Replacement From Subclinical Atherosclerosis to Plaque Progression and Acute Coronary Events
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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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