Biological effects of aspirin and clopidogrel in a randomized cross-over study in 96 healthy volunteers.
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.
Fontana
P
P
Department of Internal Medicine, Faculty of Medicine, Division of Angiology and Hemostasis, University Hospitals of Geneva, Geneva, Switzerland. pierre.fontana@medecine.unige.ch
Nolli
S
S
Reber
G
G
de Moerloose
P
P
D000293:Adolescent; D000328:Adult; D001241:Aspirin / Q000627:therapeutic use*; D001780:Blood Coagulation Tests; D000077144:Clopidogrel; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D013929:Thromboxane B2 / Q000097:blood; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D013929:Thromboxane B2; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin