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Myocardial Blood Flow and Coronary Flow Reserve During 3 Years Following Bioresorbable Vascular Scaffold Versus Metallic Drug-Eluting Stent Implantation: The VANISH Trial Coronary fractional flow reserve in bifurcation stenoses: what have we learned? Diagnostic accuracy of intracoronary optical coherence tomography-derived fractional flow reserve for assessment of coronary stenosis severity Optimal Fluoroscopic Projections of Coronary Ostia and Bifurcations Defined by Computed Tomographic Coronary Angiography ‘Small bifurcation?’ CT myocardial mass volume measurements change therapeutic strategy in coronary artery disease Reply: Will Pulmonary Artery Denervation Really Have a Place in the Armamentarium of the Pulmonary Hypertension Specialist? Coronary CT Angiographic and Flow Reserve-Guided Management of Patients With Stable Ischemic Heart Disease One Versus 2-stent Strategy for the Treatment of Bifurcation Lesions in the Context of a Coronary Chronic Total Occlusion: A Multicenter Registry T and small protrusion (TAP) vs double kissing crush technique: Insights from in-vitro models Classification and treatment of coronary artery bifurcation lesions: putting the Medina classification to the test

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.