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Ticagrelor Monotherapy Versus Dual-Antiplatelet Therapy After PCI: An Individual Patient-Level Meta-Analysis Global Approach to High Bleeding Risk Patients With Polymer-Free Drug-Coated Coronary Stents: The LF II Study Safety and efficacy of the bioabsorbable polymer everolimus-eluting stent versus durable polymer drug-eluting stents in high-risk patients undergoing PCI: TWILIGHT-SYNERGY Optimal duration of dual antiplatelet therapy after drug-eluting stent implantation: a randomized, controlled trial. Ticagrelor Monotherapy Versus Ticagrelor With Aspirin in Patients With ST-Segment Elevation Myocardial Infarction Long-term pharmacodynamic effects of Ticagrelor versus Clopidogrel in fibrinolytic-treated STEMI patients undergoing early PCI Pooled Analysis of Bleeding, Major Adverse Cardiovascular Events, and All-Cause Mortality in Clinical Trials of Time-Constrained Dual-Antiplatelet Therapy After Percutaneous Coronary Intervention Impact of bleeding during dual antiplatelet therapy in patients with coronary artery disease Conceptual Framework for Addressing Residual Atherosclerotic Cardiovascular Disease Risk in the Era of Precision Medicine A Prospective, Multicenter, Randomized, Open-label Trial to Compare Efficacy and Safety of Clopidogrel vs. Ticagrelor in Stabilized Patients with Acute Myocardial Infarction after Percutan eous Coronary Intervention: rationale and design of the TALOS-AMI trial

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.