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Closure of Iatrogenic Atrial Septal Defect Following Transcatheter Mitral Valve Repair: The Randomized MITHRAS Trial Percutaneous Closure of the Left Atrial Appendage Versus Warfarin Therapy for Prevention of Stroke in Patients With Atrial Fibrillation: A Randomised Non-Inferiority Trial Association Between Malignant Mitral Valve Prolapse and Sudden Cardiac Death: A Review Prevalence of potential drug-drug interactions in cancer patients treated with oral anticancer drugs Benefits with drug-coated balloon as compared to a conventional revascularization strategy for the treatment of coronary and non-coronary arterial disease: a comprehensive meta-analysis of 45 randomized trials Optical Coherence Tomography to Assess Proximal Side Optimization Technique in Crush Stenting Thrombotic Risk and Antithrombotic Strategies After Transcatheter Mitral Valve Replacement Transcatheter Interventions for Tricuspid Valve Disease: What to Do and Who to Do it On Initial experience with percutaneous mitral valve repair in patients with cardiac amyloidosis Italian Society of Interventional Cardiology (GIse) Registry Of Transcatheter Treatment of Mitral Valve RegurgitaTiOn (GIOTTO): Impact of Valve Disease Etiology and Residual Mitral Regurgitation after MitraClip Implantation

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.