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Biological effects of aspirin and clopidogrel in a randomized cross-over study in 96 healthy volunteers

P Fontana1, S Nolli, G Reber

  • 1Department of Internal Medicine, Faculty of Medicine, Division of Angiology and Hemostasis, University Hospitals of Geneva, Geneva, Switzerland. pierre.fontana@medecine.unige.ch

Journal of Thrombosis and Haemostasis : JTH
|April 26, 2006
PubMed

Insights

True aspirin resistance is rare in healthy individuals. Aspirin pseudo-resistance, a common finding, does not impact clopidogrel responsiveness, suggesting distinct mechanisms for antiplatelet drug efficacy.

Area of Science:

  • Pharmacology
  • Cardiovascular Medicine
  • Clinical Investigation

Background:

  • Emerging data suggest that biological resistance to antiplatelet agents like aspirin and clopidogrel may impact patient outcomes.
  • Understanding individual responses to these critical medications is essential for optimizing cardiovascular disease management.

Purpose of the Study:

  • To investigate the relationship between aspirin and clopidogrel responsiveness in healthy subjects.
  • To differentiate between true aspirin resistance and pseudo-resistance and assess their impact on clopidogrel response.

Main Methods:

  • A randomized crossover study involving 96 healthy subjects.
  • Administration of aspirin (100 mg/day) and clopidogrel (300 mg loading, 75 mg maintenance) in sequential or reverse order, with a washout period.
  • Assessment of drug effects using serum Thromboxane B2 (TxB2) assay, platelet aggregation tests, and Platelet Function Analyzer (PFA-100) and VerifyNow assays.

Main Results:

  • True aspirin resistance, defined by elevated TxB2 levels and confirmed ex vivo, was observed in only one subject.
  • A significant proportion (29%) of subjects exhibited aspirin pseudo-resistance (normal PFA-100 despite reduced TxB2), which was not associated with altered clopidogrel responsiveness.
  • No association was found between common platelet receptor gene polymorphisms and responsiveness to either aspirin or clopidogrel.

Conclusions:

  • True aspirin resistance is infrequent in the healthy population.
  • Aspirin pseudo-resistance is a distinct phenomenon not linked to clopidogrel responsiveness in healthy individuals.
  • These findings highlight the rarity of true aspirin resistance and the lack of cross-reactivity with clopidogrel response in healthy subjects.
Abstract

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