Clopidogrel Pharmacogenetics: State-of-the-Art Review and the TAILOR-PCI Study

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...

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Published inCirculation. Cardiovascular interventions Vol. 12; no. 4; p. e007811
Main Authors Pereira, Naveen L., Rihal, Charanjit S., So, Derek Y.F., Rosenberg, Yves, Lennon, Ryan J., Mathew, Verghese, Goodman, Shaun G., Weinshilboum, Richard M., Wang, Liewei, Baudhuin, Linnea M., Lerman, Amir, Hasan, Ahmed, Iturriaga, Erin, Fu, Yi-Ping, Geller, Nancy, Bailey, Kent, Farkouh, Michael E.
Format Journal Article
LanguageEnglish
Published American Heart Association, Inc 01.04.2019
Online AccessGet full text
ISSN1941-7640
1941-7632
DOI10.1161/CIRCINTERVENTIONS.119.007811

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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.
AbstractList 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.
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.
Common genetic variation in CYP2C19 (*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 PCI. 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 PCI is not recommended by clinical guidelines due to lack of prospective evidence. To address this critical gap, TAILOR-PCI is a large, pragmatic, randomized trial comparing point-of-care genotype-guided anti-platelet therapy with routine care to determine whether identifying CYP2C19 loss-of-function allele patients prospectively and prescribing alternative anti-platelet therapy is beneficial.
Author So, Derek Y.F.
Iturriaga, Erin
Geller, Nancy
Rosenberg, Yves
Weinshilboum, Richard M.
Wang, Liewei
Rihal, Charanjit S.
Lerman, Amir
Lennon, Ryan J.
Mathew, Verghese
Goodman, Shaun G.
Fu, Yi-Ping
Pereira, Naveen L.
Hasan, Ahmed
Farkouh, Michael E.
Bailey, Kent
Baudhuin, Linnea M.
AuthorAffiliation Department of Cardiovascular Medicine (N.L.P., C.S.R., A.L.), Mayo Clinic, Rochester, MN. Department of Health Sciences Research (R.J.L., K.B.), Mayo Clinic, Rochester, MN. Department of Molecular Pharmacology and Experimental Therapeutics (N.L.P., R.M.W., L.W.), Mayo Clinic, Rochester, MN. Department of Laboratory Medicine and Pathology (L.M.B.), Mayo Clinic, Rochester, MN. University of Ottawa Heart Institute, Ontario, Canada (D.Y.F.S.). National Heart, Lung, and Blood Institute, Bethesda, MD (Y.R., A.H., E.I., Y.-P.F., N.G.). Division of Cardiology, Loyola University Health System, Loyola University Chicago Stritch School of Medicine, Maywood, IL (V.M.). St. Michael’s Hospital, University of Toronto, Ontario, Canada (S.G.G.). Peter Munk Cardiac Centre, Heart and Stroke Richard Lewar Centre, University of Toronto, Canada (M.E.F.)
AuthorAffiliation_xml – name: Department of Cardiovascular Medicine (N.L.P., C.S.R., A.L.), Mayo Clinic, Rochester, MN. Department of Health Sciences Research (R.J.L., K.B.), Mayo Clinic, Rochester, MN. Department of Molecular Pharmacology and Experimental Therapeutics (N.L.P., R.M.W., L.W.), Mayo Clinic, Rochester, MN. Department of Laboratory Medicine and Pathology (L.M.B.), Mayo Clinic, Rochester, MN. University of Ottawa Heart Institute, Ontario, Canada (D.Y.F.S.). National Heart, Lung, and Blood Institute, Bethesda, MD (Y.R., A.H., E.I., Y.-P.F., N.G.). Division of Cardiology, Loyola University Health System, Loyola University Chicago Stritch School of Medicine, Maywood, IL (V.M.). St. Michael’s Hospital, University of Toronto, Ontario, Canada (S.G.G.). Peter Munk Cardiac Centre, Heart and Stroke Richard Lewar Centre, University of Toronto, Canada (M.E.F.)
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Snippet 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...
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...
Common genetic variation in CYP2C19 (*2 and *3 alleles) leads to a loss of functional protein and carriers of these loss-of-function alleles when treated with...
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Title Clopidogrel Pharmacogenetics: State-of-the-Art Review and the TAILOR-PCI Study
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