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Pooled Analysis of Bleeding, Major Adverse Cardiovascular Events, and All-Cause Mortality in Clinical Trials of Time-Constrained Dual-Antiplatelet Therapy After Percutaneous Coronary Intervention A randomized clinical study comparing double kissing crush with provisional stenting for treatment of coronary bifurcation lesions: results from the DKCRUSH-II (Double Kissing Crush versus Provisional Stenting Technique for Treatment of Coronary Bifurcation Lesions) trial Acute Coronary Syndrome, Antiplatelet Therapy, and Bleeding: A Clinical Perspective Benefit-risk profile of extended dual antiplatelet therapy beyond 1 year in patients with high risk of ischemic or bleeding events after PCI Percutaneous coronary intervention in left main coronary artery disease: the 13th consensus document from the European Bifurcation Club Revascularization of left main coronary artery Use of Risk Assessment Tools to Guide Decision-Making in the Primary Prevention of Atherosclerotic Cardiovascular Disease : A Special Report From the American Heart Association and American College of Cardiology Acute Aortic Syndrome Revisited: JACC State-of-the-Art Review 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Dual-Antiplatelet Therapy Cessation and Cardiovascular Risk in Relation to Age: Analysis From the PARIS Registry
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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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