Sex differences in platelet reactivity and response to low-dose aspirin therapy

Context Recent randomized trials suggest that women may not accrue the same cardioprotective benefits as men do from low-dose aspirin therapy used in primary prevention. Failure of aspirin to suppress platelet aggregation in women is one hypothesized mechanism. Objective To examine differential platelet reactivity to low-dose aspirin therapy by sex. Design, Setting, and Participants A clinical trial of aspirin at 81 mg/d for 14 days was conducted in 571 men and 711 women. Baseline and post - aspirin therapy measures included platelet aggregation to arachidonic acid, adenosine diphosphate, epinephrine, and platelet function analyzer closure time. Main Outcome Measure Sex differences in cyclooxygenase 1 (COX-1) direct and indirect platelet activation pathways before and after administration of aspirin. Results In 10 of the 12 platelet agonist exposures, women's platelets were significantly more reactive at baseline. However, after aspirin therapy, the percent aggregation to arachidonic acid ( the direct COX-1 pathway) decreased more in women than in men ( P <. 001) and demonstrated near total suppression of residual platelet reactivity in both men and women. In COX-1 indirect pathways, women experienced the same or more platelet inhibition than men in 8 of the 9 assays yet retained modestly greater platelet reactivity after aspirin therapy. In multivariable analysis, female sex significantly predicted aggregation to 2 mu M and 10 mu M of adenosine diphosphate (P=. 02 and <. 001, respectively) and collagen at 5 mu g/mL ( P <. 001) independent of risk factors, age, race, menopausal status, and hormone therapy. Conclusions Women experienced the same or greater decreases in platelet reactivity after aspirin therapy, retaining modestly more platelet reactivity compared with men. However, most women achieved total suppression of aggregation in the direct COX-1 pathway, the putative mechanism for aspirin's cardioprotection.