Summary

The antiplatelet effect of aspirin varies individually. This studyevaluated whether the antiplatelet effect of aspirin associateswith polymorphisms in the genes coding for cyclo-oxygenase-1(COX-1) and several platelet glycoprotein (GP) receptors in patientswith stable coronary artery disease (CAD). Bloodsamples were collected from 101 aspirin-treated (mean 100mg/d) patients. Compliance to treatment was assessed by plasmasalicylate measurement. Platelet functions were assessed bytwo methods: 1) Response to arachidonic acid (AA, 1.5 mmol/Lin aggregometry, and 2) PFA-100, evaluating platelet activationunder high shear stress in the presence of collagen and epinephrine(CEPI). Aspirin non-response was defined as: 1) slopesteeper than 12%/min inAA-aggregations,and 2) by closure timeshorter than 170 s in PFA-100.The methods used detected differentindividuals as being aspirin non-responders. Five and 21 patients, respectively, were non-responders according to AA-inducedaggregation and PFA-100. Increased plasma thromboxaneB 2 levels correlated with poor aspirin-response measured withboth AA-induced aggregations and PFA-100 (P=0.02 andP=0.003, respectively). Of the non-responders detected by AA,3 of 5 (60%) carried the rare G allele for the -A842G polymorphismof COX-1 in contrast to 16 of 96 (17%) responders(P=0.016). Diabetes was associated with poor response.Aspirinnon-response detected by PFA-100 associated with C13254Tpolymorphism of GP VI and female gender (P=0.012 andP=0.019, respectively). Although two patients were possiblynon-compliant, this did not effect present conclusions. Evaluationof aspirin efficacy by AA-induced aggregation and PFA-100detected different individuals, with different genotypic profiles,as being aspirin non-responders.