Clopidogrel Resistance

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

Research output: Chapter in Book/Report/Conference proceedingChapter

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 languageEnglish (US)
Title of host publicationAntiplatelet Therapy in Cardiovascular Disease
PublisherWiley-Blackwell
Pages285-292
Number of pages8
ISBN (Electronic)9781118493984
ISBN (Print)9781118275757
DOIs
StatePublished - Jun 3 2014

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Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Tantry, U. S., Bliden, K. P., Meeran, T., & Gurbel, P. A. (2014). Clopidogrel Resistance. In Antiplatelet Therapy in Cardiovascular Disease (pp. 285-292). Wiley-Blackwell. https://doi.org/10.1002/9781118493984.ch34