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Heart Failure With Recovered Left Ventricular Ejection Fraction: JACC Scientific Expert Panel Lipid-Modifying Agents, From Statins to PCSK9 Inhibitors: JACC Focus Seminar Impact of Lesion Preparation Strategies on Outcomes of Left Main PCI: The EXCEL Trial Third-Generation Balloon and Self-Expandable Valves for Aortic Stenosis in Large and Extra-Large Aortic Annuli From the TAVR-LARGE Registry Randomized study to evaluate sirolimus-eluting stents implanted at coronary bifurcation lesions Economic and Quality-of-Life Outcomes of Natriuretic Peptide–Guided Therapy for Heart Failure Six-month versus 12-month dual antiplatelet therapy after implantation of drug-eluting stents: the Efficacy of Xience/Promus Versus Cypher to Reduce Late Loss After Stenting (EXCELLENT) randomized, multicenter study Effects of Intravascular Ultrasound-Guided Versus Angiography-Guided New-Generation Drug-Eluting Stent Implantation: Meta-Analysis With Individual Patient-Level Data From 2,345 Randomized Patients Dual-antiplatelet treatment beyond 1 year after drug-eluting stent implantation (ARCTIC-Interruption): a randomised trial Chimney technique in a TAVR-in-TAVR procedure with high risk of left main artery ostium occlusion
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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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