Clopidogrel resistance: fact and fiction

J W van Werkum1, A A C M Heestermans, V H M Deneer

  • 1Department of Cardiology, St. Antonius Hospital, Nieuwegein, The Netherlands.

Future Cardiology
|October 7, 2009
PubMed

Insights

Clopidogrel with aspirin reduces thrombotic events, but response varies greatly. Understanding factors like absorption and drug interactions is key to managing clopidogrel resistance.

Area of Science:

  • Pharmacology
  • Cardiology
  • Thrombosis Research

Background:

  • Clopidogrel and aspirin combination therapy is vital for preventing thrombotic events in acute coronary syndromes and after percutaneous coronary intervention.
  • Significant interindividual variability in patient response to clopidogrel necessitates further investigation.

Purpose of the Study:

  • To explore the factors contributing to variable patient responses to clopidogrel.
  • To highlight the clinical relevance and prevalence of inadequate clopidogrel response.
  • To recommend future research directions for assessing clopidogrel resistance.

Main Methods:

  • Review of existing literature on clopidogrel response variability.
  • Identification of factors influencing clopidogrel efficacy, including dosing, absorption, drug metabolism (CYP450 3A4/5), drug interactions, and genetic polymorphisms.
  • Discussion of various platelet function assays used to measure clopidogrel response.

Main Results:

  • Inadequate clopidogrel response rates vary widely based on measurement methods and definitions.
  • Factors such as dosing, intestinal absorption, CYP450 activity, drug-drug interactions, and genetic variations impact clopidogrel response.
  • Clinical relevance of inadequate clopidogrel response has been demonstrated in recent studies.

Conclusions:

  • Accurate assessment of clopidogrel resistance requires standardized, sensitive assays focusing on P2Y12 receptor inhibition.
  • Future research should utilize rapid, simple tests like vasodilator-stimulated phosphoprotein (VASP) assay or platelet aggregate stabilization measurements.
  • Understanding and addressing clopidogrel resistance is crucial for optimizing antiplatelet therapy outcomes.

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