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Risk of Coronary Obstruction and Feasibility of Coronary Access After Repeat Transcatheter Aortic Valve Replacement With the Self-Expanding Evolut Valve: A Computed Tomography Simulation Study Baseline Characteristics and Risk Profiles of Participants in the ISCHEMIA Randomized Clinical Trial Mechanisms of in-stent restenosis after drug-eluting stent implantation: intravascular ultrasound analysis Osteoarthritis risk is reduced after treatment with ticagrelor compared to clopidogrel: a propensity score matching analysis High-Risk Coronary Plaque Regression After Intensive Lifestyle Intervention in Nonbstructive Coronary Disease: A Randomized Study Single Versus Dual Antiplatelet Therapy Following TAVR: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Impact of myocardial fibrosis on left ventricular remodelling, recovery, and outcome after transcatheter aortic valve implantation in different haemodynamic subtypes of severe aortic stenosis Comparison of 1-Year Pre- And Post-Transcatheter Aortic Valve Replacement Hospitalization Rates: A Population-Based Cohort Study Right ventricular function and outcome in patients undergoing transcatheter aortic valve replacement Prospective application of pre-defined intravascular ultrasound criteria for assessment of intermediate left main coronary artery lesions results from the multicenter LITRO study

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.