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The contribution of tissue-grouped BMI-associated gene sets to cardiometabolic-disease risk: a Mendelian randomization study 5-Year Outcomes After TAVR With Balloon-Expandable Versus Self-Expanding Valves: Results From the CHOICE Randomized Clinical Trial Balloon Aortic Valvuloplasty as a Bridge to Aortic Valve Replacement: A Contemporary Nationwide Perspective Thrombotic Versus Bleeding Risk After Transcatheter Aortic Valve Replacement: JACC Review Topic of the Week 2020 ACC Expert Consensus Decision Pathway on Management of Conduction Disturbances in Patients Undergoing Transcatheter Aortic Valve Replacement A Report of the American College of Cardiology Solution Set Oversight Committee Higher neutrophil-to-lymphocyte ratio (NLR) increases the risk of suboptimal platelet inhibition and major cardiovascular ischemic events among ACS patients receiving dual antiplatelet therapy with ticagrelor EXCELling in Left Main Intervention Serial intravascular ultrasound analysis of the main and side branches in bifurcation lesions treated with the T-stenting technique Effects of Icosapent Ethyl on Total Ischemic Events: From REDUCE-IT Transcatheter Aortic Valve Replacement: Role of Multimodality Imaging in Common and Complex Clinical Scenarios
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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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