Summary
The antiplatelet effect of aspirin varies individually. This study evaluated whether
the antiplatelet effect of aspirin associates with polymorphisms in the genes coding
for cyclo-oxygenase-1 (COX-1) and several platelet glycoprotein (GP) receptors in
patients with stable coronary artery disease (CAD). Blood samples were collected from
101 aspirin-treated (mean 100 mg/d) patients. Compliance to treatment was assessed
by plasma salicylate measurement. Platelet functions were assessed by two methods:
1) Response to arachidonic acid (AA, 1.5 mmol/L in aggregometry, and 2) PFA-100, evaluating
platelet activation under high shear stress in the presence of collagen and epinephrine
(CEPI). Aspirin non-response was defined as: 1) slope steeper than 12%/min in AA-aggregations,and
2) by closure time shorter than 170 s in PFA-100. The methods used detected different
individuals as being aspirin non-responders. Five and 21 patients, respectively, were
non-responders according to AA-induced aggregation and PFA-100. Increased plasma thromboxane
B2 levels correlated with poor aspirin-response measured with both AA-induced aggregations
and PFA-100 (P=0.02 and P=0.003, respectively). Of the non-responders detected by
AA, 3 of5 (60%) carried the rareG allele for the -A842G polymorphism of COX-1 in contrast
to 16 of 96 (17%) responders (P=0.016). Diabetes was associated with poor response.
Aspirin non-response detected by PFA-100 associated with C13254T polymorphism of GP
VI and female gender (P=0.012 and P=0.019, respectively). Although two patients were
possibly non-compliant, this did not effect present conclusions. Evaluation of aspirin
efficacy by AA-induced aggregation and PFA-100 detected different individuals, with
different genotypic profiles, as being aspirin non-responders.
Keywords
Aspirin - cyclo-oxygenase-1 - genotype - glycoprotein VI - coronary artery disease