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International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial: Rationale and design SR-B1 Drives Endothelial Cell LDL Transcytosis via DOCK4 to Promote Atherosclerosis Empagliflozin, Health Status, and Quality of Life in Patients with Heart Failure and Preserved Ejection Fraction: The EMPEROR-Preserved Trial Guideline Update on Indications for Transcatheter Aortic Valve Implantation Based on the 2020 American College of Cardiology/American Heart Association Guidelines for Management of Valvular Heart Disease Angiographic derived endothelial shear stress: a new predictor of atherosclerotic disease progression Flow-Regulated Endothelial S1P Receptor-1 Signaling Sustains Vascular Development Randomized Comparison Between Everolimus-Eluting Bioresorbable Scaffold and Metallic Stent: Multimodality Imaging Through 3 Years Abnormalities in 3-Dimensional Left Ventricular Mechanics With Anthracycline Chemotherapy Are Associated With Systolic and Diastolic Dysfunction Evaluation and Management of Aortic Stenosis in Chronic Kidney Disease: A Scientific Statement From the American Heart Association Active factor XI is associated with the risk of cardiovascular events in stable coronary artery disease patients
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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.

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