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Quantitative angiography methods for bifurcation lesions: a consensus statement update from the European Bifurcation Club Management of Acute Myocardial Infarction During the COVID-19 Pandemic IVUS Guidance Is Associated With Better Outcome in Patients Undergoing Unprotected Left Main Coronary Artery Stenting Compared With Angiography Guidance Alone From Nonclinical Research to Clinical Trials and Patient-registries: Challenges and Opportunities in Biomedical Research High-Risk Coronary Atherosclerosis: Is It the Plaque Burden, the Calcium, the Lipid, or Something Else? HFpEF: From Mechanisms to Therapies Prognostic Effect and Longitudinal Hemodynamic Assessment of Borderline Pulmonary Hypertension Comparative analysis of recurrent events after presentation with an index myocardial infarction or ischaemic stroke Current Interventions for the Left Main Bifurcation Antithrombotic Therapy in Patients with Atrial Fibrillation and Acute Coronary Syndrome Treated Medically or with Percutaneous Coronary Intervention or Undergoing Elective Percutaneous Coronary Intervention: Insights from the AUGUSTUS 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.