Clopidogrel Resistance

Udaya S. Tantry; Kevin P. Bliden; Talha Meeran; Paul A. Gurbel

doi:10.1002/9781118493984.ch34

Clopidogrel Resistance

Udaya S. Tantry, Kevin P. Bliden, Talha Meeran, Paul A. Gurbel

Research output: Chapter in Book/Report/Conference proceeding › Chapter

2 Scopus citations

Abstract

A large body of data from observational studies indicates that clopidogrel therapy is associated with major pharmacodynamic (PD) limitations including wide response variability and nonresponsiveness (high on-treatment platelet reactivity (HPR) to adenosine diphosphate (ADP)) that have been linked to post-percutaneous coronary intervention (PCI) ischemic event occurrence, including stent thrombosis (ST). Insufficient active metabolite generation is the primary explanations for clopidogrel nonresponsiveness, and it is due to (i) variable or limited intestinal absorption that may be influenced by ABCB1 gene polymorphism and (ii) functional variability in P450 isoenzyme activity that is influenced by drug-drug interactions (DDI) and single nucleotide polymorphisms (SNPs) in genes encoding CYP450 isoenzymes. Treatment with high-dose clopidogrel (600mg loading dose plus 150mg maintenance dose) is not an optimal strategy to overcome clopidogrel HPR and to reduce recurrent ischemic event occurrence, and more potent P2Y12 receptor blockers, such as prasugrel and ticagrelor, are credible alternative strategies to overcome HPR during clopidogrel therapy.

Original language	English (US)
Title of host publication	Antiplatelet Therapy in Cardiovascular Disease
Publisher	Wiley-Blackwell
Pages	285-292
Number of pages	8
ISBN (Electronic)	9781118493984
ISBN (Print)	9781118275757
DOIs	https://doi.org/10.1002/9781118493984.ch34
State	Published - Jun 3 2014
Externally published	Yes

Keywords

Clopidogrel
High on-treatment platelet reactivity
Ischemic vent
Nonresponsiveness
Percutaneous coronary intervention
Prasugrel
Stent thrombosis
Ticagrelor

ASJC Scopus subject areas

General Medicine

Access to Document

10.1002/9781118493984.ch34

Cite this

@inbook{a65b8eb600f449dea90dd67f018eca8d,

title = "Clopidogrel Resistance",

abstract = "A large body of data from observational studies indicates that clopidogrel therapy is associated with major pharmacodynamic (PD) limitations including wide response variability and nonresponsiveness (high on-treatment platelet reactivity (HPR) to adenosine diphosphate (ADP)) that have been linked to post-percutaneous coronary intervention (PCI) ischemic event occurrence, including stent thrombosis (ST). Insufficient active metabolite generation is the primary explanations for clopidogrel nonresponsiveness, and it is due to (i) variable or limited intestinal absorption that may be influenced by ABCB1 gene polymorphism and (ii) functional variability in P450 isoenzyme activity that is influenced by drug-drug interactions (DDI) and single nucleotide polymorphisms (SNPs) in genes encoding CYP450 isoenzymes. Treatment with high-dose clopidogrel (600mg loading dose plus 150mg maintenance dose) is not an optimal strategy to overcome clopidogrel HPR and to reduce recurrent ischemic event occurrence, and more potent P2Y12 receptor blockers, such as prasugrel and ticagrelor, are credible alternative strategies to overcome HPR during clopidogrel therapy.",

keywords = "Clopidogrel, High on-treatment platelet reactivity, Ischemic vent, Nonresponsiveness, Percutaneous coronary intervention, Prasugrel, Stent thrombosis, Ticagrelor",

author = "Tantry, {Udaya S.} and Bliden, {Kevin P.} and Talha Meeran and Gurbel, {Paul A.}",

note = "Funding Information: Dr. Gurbel has a research grant from Schering and Millenium in the last 2 years studying antiplatelet effects of clopidogrel and eptifibatide in elective stenting. Dr. Gurbel has a research grant from Astra Zeneca in the last 2 years studying antiplatelet effects of clopidogrel in relation to stent thrombosis. Dr. Gurbel has a research grant from Bayer in the last 2 years studying antiplatelet effects of aspirin in outpatients. Dr. Gurbel has a research grant from Astra Zeneca in the last 2 years studying antiplatelet effects of AZD6140 in elective stenting. Dr. Gurbel has a research grant from Haemoscope and NIH in the last 2 years studying physical properties of clot formation and recurrent ischemic events post-elective stenting. Dr. Gurbel has been a co-investigator in the last 2 years for Medtronic and Boston Scientific studying new drug-eluting stents in elective stenting. Dr. Gurbel was a scientific officer for a start-up company — Thromboscience that is no longer in existence. Dr. Gurbel serves as consultant for Astra Zeneca, Lilly, Sanofi, Bayer, and the Medicines Company. There is no conflict of interest for other authors. Publisher Copyright: {\textcopyright} 2014 by John Wiley & Sons, Ltd. All rights reserved.",

year = "2014",

month = jun,

day = "3",

doi = "10.1002/9781118493984.ch34",

language = "English (US)",

isbn = "9781118275757",

pages = "285--292",

booktitle = "Antiplatelet Therapy in Cardiovascular Disease",

publisher = "Wiley-Blackwell",

}

TY - CHAP

T1 - Clopidogrel Resistance

AU - Tantry, Udaya S.

AU - Bliden, Kevin P.

AU - Meeran, Talha

AU - Gurbel, Paul A.

N1 - Funding Information: Dr. Gurbel has a research grant from Schering and Millenium in the last 2 years studying antiplatelet effects of clopidogrel and eptifibatide in elective stenting. Dr. Gurbel has a research grant from Astra Zeneca in the last 2 years studying antiplatelet effects of clopidogrel in relation to stent thrombosis. Dr. Gurbel has a research grant from Bayer in the last 2 years studying antiplatelet effects of aspirin in outpatients. Dr. Gurbel has a research grant from Astra Zeneca in the last 2 years studying antiplatelet effects of AZD6140 in elective stenting. Dr. Gurbel has a research grant from Haemoscope and NIH in the last 2 years studying physical properties of clot formation and recurrent ischemic events post-elective stenting. Dr. Gurbel has been a co-investigator in the last 2 years for Medtronic and Boston Scientific studying new drug-eluting stents in elective stenting. Dr. Gurbel was a scientific officer for a start-up company — Thromboscience that is no longer in existence. Dr. Gurbel serves as consultant for Astra Zeneca, Lilly, Sanofi, Bayer, and the Medicines Company. There is no conflict of interest for other authors. Publisher Copyright: © 2014 by John Wiley & Sons, Ltd. All rights reserved.

PY - 2014/6/3

Y1 - 2014/6/3

N2 - A large body of data from observational studies indicates that clopidogrel therapy is associated with major pharmacodynamic (PD) limitations including wide response variability and nonresponsiveness (high on-treatment platelet reactivity (HPR) to adenosine diphosphate (ADP)) that have been linked to post-percutaneous coronary intervention (PCI) ischemic event occurrence, including stent thrombosis (ST). Insufficient active metabolite generation is the primary explanations for clopidogrel nonresponsiveness, and it is due to (i) variable or limited intestinal absorption that may be influenced by ABCB1 gene polymorphism and (ii) functional variability in P450 isoenzyme activity that is influenced by drug-drug interactions (DDI) and single nucleotide polymorphisms (SNPs) in genes encoding CYP450 isoenzymes. Treatment with high-dose clopidogrel (600mg loading dose plus 150mg maintenance dose) is not an optimal strategy to overcome clopidogrel HPR and to reduce recurrent ischemic event occurrence, and more potent P2Y12 receptor blockers, such as prasugrel and ticagrelor, are credible alternative strategies to overcome HPR during clopidogrel therapy.

AB - A large body of data from observational studies indicates that clopidogrel therapy is associated with major pharmacodynamic (PD) limitations including wide response variability and nonresponsiveness (high on-treatment platelet reactivity (HPR) to adenosine diphosphate (ADP)) that have been linked to post-percutaneous coronary intervention (PCI) ischemic event occurrence, including stent thrombosis (ST). Insufficient active metabolite generation is the primary explanations for clopidogrel nonresponsiveness, and it is due to (i) variable or limited intestinal absorption that may be influenced by ABCB1 gene polymorphism and (ii) functional variability in P450 isoenzyme activity that is influenced by drug-drug interactions (DDI) and single nucleotide polymorphisms (SNPs) in genes encoding CYP450 isoenzymes. Treatment with high-dose clopidogrel (600mg loading dose plus 150mg maintenance dose) is not an optimal strategy to overcome clopidogrel HPR and to reduce recurrent ischemic event occurrence, and more potent P2Y12 receptor blockers, such as prasugrel and ticagrelor, are credible alternative strategies to overcome HPR during clopidogrel therapy.

KW - Clopidogrel

KW - High on-treatment platelet reactivity

KW - Ischemic vent

KW - Nonresponsiveness

KW - Percutaneous coronary intervention

KW - Prasugrel

KW - Stent thrombosis

KW - Ticagrelor

UR - http://www.scopus.com/inward/record.url?scp=84926405416&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84926405416&partnerID=8YFLogxK

U2 - 10.1002/9781118493984.ch34

DO - 10.1002/9781118493984.ch34

M3 - Chapter

AN - SCOPUS:84926405416

SN - 9781118275757

SP - 285

EP - 292

BT - Antiplatelet Therapy in Cardiovascular Disease

PB - Wiley-Blackwell

ER -

Clopidogrel Resistance

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this