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10-Year Outcomes of Stents Versus Coronary Artery Bypass Grafting for Left Main Coronary Artery Disease Impact of SYNTAX Score on 10-Year Outcomes After Revascularization for Left Main Coronary Artery Disease Bayesian Interpretation of the EXCEL Trial and Other Randomized Clinical Trials of Left Main Coronary Artery Revascularization Long-Term Outcomes of Different Two-Stent Techniques With Second-Generation Drug-Eluting Stents for Unprotected Left Main Bifurcation Disease: Insights From the FAILS-2 Study Left Main Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Patients With Prior Cerebrovascular Disease: Results From the EXCEL Trial Intravascular Imaging and 12-Month Mortality After Unprotected Left Main Stem PCI: An Analysis From the British Cardiovascular Intervention Society Database Left Main Revascularization in 2017: Coronary Artery Bypass Grafting or Percutaneous Coronary Intervention? Revascularization of left main coronary artery Intravascular Imaging and 12-Month Mortality After Unprotected Left Main Stem PCI: An Analysis From the British Cardiovascular Intervention Society Database Percutaneous coronary intervention for the left main stem and other bifurcation lesions: 12th consensus document from the European Bifurcation Club
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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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