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2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure Clinical Outcomes Following Intravascular Imaging-Guided Versus Coronary Angiography-Guided Percutaneous Coronary Intervention With Stent Implantation: A Systematic Review and Bayesian Network Meta-Analysis of 31 Studies and 17,882 Patients Post-stenting fractional flow reserve vs coronary angiography for optimisation of percutaneous coronary intervention: TARGET-FFR trial Rationale and design of a randomized clinical trial comparing safety and efficacy of Myval transcatheter heart valve versus contemporary transcatheter heart valves in patients with severe symptomatic aortic valve stenosis: the LANDMARK trial Revascularization in Patients With Left Main Coronary Artery Disease and Left Ventricular Dysfunction Correlations between fractional flow reserve and intravascular ultrasound in patients with an ambiguous left main coronary artery stenosis Coronary Access After TAVR With a Self-Expanding Bioprosthesis: Insights From Computed Tomography Diagnostic accuracy of cardiac positron emission tomography versus single photon emission computed tomography for coronary artery disease: a bivariate meta-analysis Comparison of Early Surgical or Transcatheter Aortic Valve Replacement Versus Conservative Management in Low-Flow, Low-Gradient Aortic Stenosis Using Inverse Probability of Treatment Weighting: Results From the TOPAS Prospective Observational Cohort Study Stroke Rates Following Surgical Versus Percutaneous Coronary Revascularization

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.