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Left Main Revascularization With PCI or CABG in Patients With Chronic Kidney Disease: EXCEL Trial Intravascular Ultrasound to Guide Left Main Stem Intervention: A Sub-Study of the NOBLE Trial Percutaneous coronary intervention versus coronary artery bypass grafting in patients with three-vessel or left main coronary artery disease: 10-year follow-up of the multicentre randomised controlled SYNTAX trial Design and rationale for a randomised comparison of everolimus-eluting stents and coronary artery bypass graft surgery in selected patients with left main coronary artery disease: the EXCEL trial Operator Experience and Outcomes After Left Main Percutaneous Coronary Intervention Percutaneous Coronary Intervention vs Coronary Artery Bypass Grafting in Patients With Left Main Coronary Artery Stenosis: A Systematic Review and Meta-analysis Impact of Lesion Preparation Strategies on Outcomes of Left Main PCI: The EXCEL Trial Sex differences in left main coronary artery stenting: Different characteristics but similar outcomes for women compared with men Quality of Life after Everolimus-Eluting Stents or Bypass Surgery for Treatment of Left Main Disease Successful bailout stenting strategy against lethal coronary dissection involving left main bifurcation

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.