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The Tricuspid Annular Plane Systolic Excursion to Systolic Pulmonary Artery Pressure Index: Association With All-Cause Mortality in Patients With Moderate or Severe Tricuspid Regurgitation Five-Year Clinical Outcomes After Drug-Eluting Stent Implantation Following Rotational Atherectomy for Heavily Calcified Lesions Orbital atherectomy for the treatment of small (2.5mm) severely calcified coronary lesions: ORBIT II sub-analysis Risk of Atrial Fibrillation According to Cancer Type: A Nationwide Population-Based Study Incidence and Standardized Definitions of Mitral Valve Leaflet Adverse Events After Transcatheter Mitral Valve Repair: the EXPAND Study Pathophysiology, diagnosis and new therapeutic approaches for ischemic mitral regurgitation An artificial intelligence-enabled ECG algorithm for the identification of patients with atrial fibrillation during sinus rhythm: a retrospective analysis of outcome prediction Novel Transcatheter Mitral Valve Prosthesis for Patients With Severe Mitral Annular Calcification Outcomes of TTVI in Patients With Pacemaker or Defibrillator Leads: Data From the TriValve Registry Cardio-Oncology Services: rationale, organization, and implementation: A report from the ESC Cardio-Oncology council

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.