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Sirolimus-eluting stent implantation for unprotected left main coronary artery stenosis: comparison with bare metal stent implantation Access Site and Outcomes for Unprotected Left Main Stem Percutaneous Coronary Intervention: An Analysis of the British Cardiovascular Intervention Society Database Impact of chronic obstructive pulmonary disease on prognosis after percutaneous coronary intervention and bypass surgery for left main coronary artery disease: an analysis from the EXCEL trial Long-Term Clinical Outcomes and Optimal Stent Strategy in Left Main Coronary Bifurcation Stenting C-reactive protein and prognosis after percutaneous coronary intervention and bypass graft surgery for left main coronary artery disease: Analysis from the EXCEL trial Restricted access Mortality After Repeat Revascularization Following PCI or CABG for Left Main Disease: The EXCEL Trial Self-expandable sirolimus-eluting stents compared to second-generation drug-eluting stents for the treatment of the left main: A propensity score analysis from the SPARTA and the FAILS-2 registries Left main coronary angioplasty: early and late results of 127 acute and elective procedures Impact of large periprocedural myocardial infarction on mortality after percutaneous coronary intervention and coronary artery bypass grafting for left main disease: an analysis from the EXCEL trial Long-term safety and effectiveness of unprotected left main coronary stenting with drug-eluting stents compared with bare-metal stents

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.