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

J Thromb Haemost. 2006 Apr;4(4):813-9. doi: 10.1111/j.1538-7836.2006.01867.x.


Background: Some data suggest that biological 'resistance' to aspirin or clopidogrel may influence clinical outcome.

Objective: The aim of this study was to evaluate the relationship between aspirin and clopidogrel responsiveness in healthy subjects.

Methods: Ninety-six healthy subjects were randomly assigned to receive a 1-week course of aspirin 100 mg day(-1) followed by a 1-week course of clopidogrel (300 mg on day 1, then 75 mg day(-1)), or the reverse sequence, separated by a 2-week wash-out period. The drug effects were assessed by means of serum TxB2 assay, platelet aggregation tests, and the PFA -100 and Ultegra RPFA -Verify Now methods.

Results: Only one subject had true aspirin resistance, defined as a serum TxB2 level > 80 pg microL(-1) at the end of aspirin administration and confirmed by platelet incubation with aspirin. PFA-100 values were normal in 29% of the subjects after aspirin intake, despite a drastic reduction in TxB2 production; these subjects were considered to have aspirin pseudo-resistance. Clopidogrel responsiveness was not related to aspirin pseudo-resistance. Selected polymorphisms of platelet receptor genes were not associated with either aspirin or clopidogrel responsiveness.

Conclusions: In healthy subjects, true aspirin resistance is rare and aspirin pseudo-resistance is not related to clopidogrel responsiveness.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aspirin / therapeutic use*
  • Blood Coagulation Tests
  • Clopidogrel
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Humans
  • Male
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Polymorphism, Genetic
  • Thromboxane B2 / blood
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use
  • Treatment Outcome


  • Platelet Aggregation Inhibitors
  • Thromboxane B2
  • Clopidogrel
  • Ticlopidine
  • Aspirin