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Adjunctive Cilostazol to Dual Antiplatelet Therapy to Enhance Mobilization of Endothelial Progenitor Cell in Patients with Acute Myocardial Infarction: A Randomized, Placebo-Controlled EPISODE Trial Long-term dual antiplatelet-induced intestinal injury resulting in translocation of intestinal bacteria into blood circulation increased the incidence of adverse events after PCI in patients with coronary artery disease Polymer-based or Polymer-free Stents in Patients at High Bleeding Risk ISAR-SAFE: a randomized, double-blind, placebo-controlled trial of 6 vs. 12 months of clopidogrel therapy after drug-eluting stenting 6-Month Versus 12-Month Dual-Antiplatelet Therapy Following Long Everolimus-Eluting Stent Implantation: The IVUS-XPL Randomized Clinical Trial Dual Antiplatelet Therapy after PCI in Patients at High Bleeding Risk Prasugrel versus clopidogrel in patients with acute coronary syndromes Patient-tailored antithrombotic therapy following percutaneous coronary intervention Management of Antithrombotic Therapy in Atrial Fibrillation Patients Undergoing PCI: JACC State-of-the-Art Review Cost-Effectiveness of Different Durations of Dual-Antiplatelet Use After Percutaneous Coronary Intervention

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.