Antiplatelet drug resistance and variability in response: the role of antiplatelet therapy monitoring.

Published

Journal Article (Review)

Dual antiplatelet therapy of clopidogrel added aspirin is an established treatment strategy to prevent recurrent ischemic event occurrence in coronary artery disease patients. Generally, a one size fits all nonselective strategy is used without an assessment of pharmacodynamic efficacy of clopidogrel therapy. However, pharmacodynamic studies revealed various limitations of clopidogrel metabolism and numerous factors such as genetic and, drug-drug interactions influence the antiplatelet response to clopidogrel therapy. Translational platelet function investigations performed in the percutaneous coronary intervention (PCI)-treated population receiving clopidogrel have identified high platelet reactivity (HPR) to adenosine diphosphate as a major risk factor for both acute as well as long-term ischemic event occurrence, including stent thrombosis. Recent studies have highlighted the relation of single nucleotide polymorphisms of genes involved in clopidogrel absorption and metabolism to reduced pharmacokinetic and pharmacodynamic responses to clopidogrel. Cytochrome (CYP) 2C19 loss-of-function (LoF) allele carriage has been associated with increased thrombotic risk in the PCI population. However, clopidogrel is pharmacodynamically effective in about two thirds of patients undergoing PCI; these patients do not have HPR. Therefore, selectively treating two thirds of patients with generic clopidogrel may provide significant cost savings. Unselected therapy with the new P2Y12 receptor blockers is associated with increased bleeding. The introduction of generic clopidogrel holds the strong possibility of inducing a change in practice whereby genetic and platelet function testing are performed more frequently in patients receiving a stent.

Full Text

Duke Authors

Cited Authors

  • Tantry, US; Gurbel, PA

Published Date

  • January 2013

Published In

Volume / Issue

  • 19 / 21

Start / End Page

  • 3795 - 3815

PubMed ID

  • 23286432

Pubmed Central ID

  • 23286432

Electronic International Standard Serial Number (EISSN)

  • 1873-4286

International Standard Serial Number (ISSN)

  • 1381-6128

Digital Object Identifier (DOI)

  • 10.2174/1381612811319210006

Language

  • eng