Personalized antiplatelet and anticoagulation therapy: applications and significance of pharmacogenomics

Figures & data

Figure 1 Major proteins involved in clopidogrel transport and metabolism.

Note: Copyright © Pharmacogenomics Knowledge Base (PharmGKB). Reprinted by permission from the Pharmacogenomics Knowledge Base (PharmGKB) and Stanford University. Sangkuhl K, Klein TE, Altman RB. Clopidogrel pathway. Pharmacogenetics and genomics [webpage on the Internet]. PharmGKB; 2010.¹³⁶ Available from: http://www.pharmgkb.org/pathway/PA154424674. Accessed May 7, 2014.
Abbreviations: ABCB1, ATP-binding cassette subfamily B member 1; CES1, carboxylesterase 1; CYP1A2, cytochrome P450, family 1, subfamily A, polypeptide 2; CYP2C9, cytochrome P450, family 2, subfamily C, polypeptide 9; CYP2C19, cytochrome P450, family 2, subfamily C, polypeptide 19; CYP2B6, cytochrome P450, family 2, subfamily B, polypeptide 6; CYP3A4, cytochrome P450, family 3, subfamily A, polypeptide 4; CYP3A5, cytochrome P450, family 3, subfamily A, polypeptide 5; PON1, paraoxonase 1; P2RY12, purinergic receptor P2Y, G-protein coupled, 12.

Figure 2 Theoretical implementation of clopidogrel and warfarin pharmacogenomics.

Notes: (A) Increasing evidence suggests that benefit from clopidogrel pharmacogenomics is dependent on clinical indication, whereby patients with ACS undergoing PCI derive the most benefit. (B) Patient A represents a typical individual initiating warfarin therapy, while patient B represents an individual at high risk during warfarin initiation (eg, elderly, concomitant dual antiplatelet therapy, prior history of pathological bleeding, etc).
Abbreviations: ACS, acute coronary syndrome; AF, atrial fibrillation; CAD, coronary artery disease; PCI, percutaneous coronary intervention.

Figure 3 Pharmacogenetic algorithm for initiation of antiplatelet therapy based on CYP2C19 genotype recommended by the Clinical Pharmacogenetics Implementation Consortium.

Note: Adapted by permission from Macmillan Publishers Ltd: Clinical Pharmacology and Therapeutics. Scott SA, Sangkuhl K, Stein CM, et al; Clinical Pharmacogenetics Implementation Consortium. Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 1
Abbreviations: ACS, acute coronary syndrome; CYP2C19, cytochrome P450, family 2, subfamily C, member 19; EM, extensive metabolizer; IM, intermediate metabolizer; PCI, percutaneous coronary intervention; PM, poor metabolizer; UM, ultrarapid metabolizer.

SangkuhlKKleinTEAltmanRBClopidogrel pathway. Pharmacogenetics and genomics [webpage on the Internet]PharmGKB2010 Available from: http://www.pharmgkb.org/pathway/PA154424674Accessed May 7, 2014

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