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Characterization of lesions undergoing ischemia-driven revascularization after complete revascularization versus culprit lesion only in patients with STEMI and multivessel disease - A DANAMI-3-PRIMULTI substudy Association of Silent Myocardial Infarction and Sudden Cardiac Death Early versus delayed invasive intervention in acute coronary syndromes Mild Hypothermia in Cardiogenic Shock Complicating Myocardial Infarction - The Randomized SHOCK-COOL Trial Prognostic Value of SYNTAX Score in Patients With Infarct-Related Cardiogenic Shock: Insights From the CULPRIT-SHOCK Trial Risk Factors Associated With Major Cardiovascular Events 1 Year After Acute Myocardial Infarction Impact of tissue protrusion after coronary stenting in patients with ST-segment elevation myocardial infarction Impact of Percutaneous Coronary Intervention for Chronic Total Occlusion in Non-Infarct-Related Arteries in Patients With Acute Myocardial Infarction (from the COREA-AMI Registry) Early Natural History of Spontaneous Coronary Artery Dissection Subcutaneous Selatogrel Inhibits Platelet Aggregation in Patients With Acute Myocardial Infarction

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.