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'Ticagrelor alone vs. dual antiplatelet therapy from 1 month after drug-eluting coronary stenting among patients with STEMI': a post hoc analysis of the randomized GLOBAL LEADERS trial Sex-Based Outcomes in Patients With a High Bleeding Risk After Percutaneous Coronary Intervention and 1-Month Dual Antiplatelet Therapy: A Secondary Analysis of the LEADERS FREE Randomized Clinical Trial Bayesian Interpretation of the EXCEL Trial and Other Randomized Clinical Trials of Left Main Coronary Artery Revascularization Left atrial appendage occlusion in atrial fibrillation patients with previous intracranial bleeding: A national multicenter study Drug-eluting stent implantation in patients with acute coronary syndrome - the Activity of Platelets after Inhibition and Cardiovascular Events: Optical Coherence Tomography (APICE OCT) study Intravascular Imaging and 12-Month Mortality After Unprotected Left Main Stem PCI: An Analysis From the British Cardiovascular Intervention Society Database Efficacy and safety of low-dose colchicine in patients with coronary disease: a systematic review and meta-analysis of randomized trials The Science Underlying COVID-19: Implications for the Cardiovascular System Comprehensive Investigation of Circulating Biomarkers and their Causal Role in Atherosclerosis-related Risk Factors and Clinical Events Ticagrelor versus clopidogrel in elective percutaneous coronary intervention (ALPHEUS): a randomised, open-label, phase 3b trial
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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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