Effect of aspirin dose, preparation, and withdrawal on platelet response in normal volunteers.

A significant difference in individual response to aspirin therapy has been described, and studies have shown that a minimal response to aspirin may be associated with increased risk for some cardiovascular events. However, it remains unclear if aspirin dose, coating, or termination alters the antiplatelet effects of aspirin. Normal volunteers were randomly assigned to enteric-coated or uncoated aspirin 81 or 325 mg and monitored over 12 days with a point-of-care aspirin assay that incorporates the platelet agonist arachidonic acid. The antiplatelet response was greater with a 325-mg dose than with an 81-mg dose. A coating slowed the antiplatelet response to the 81-mg dose only. There were no differences among the groups after maximum response was achieved between days 4 and 7. There was significant recovery of platelet aggregation <48 hours after the cessation of aspirin, with a return to baseline values by the fifth day. A significant interpatient variation in response to the 4 dosing regimes was observed. In conclusion, the antiplatelet response was more rapid to a 325-mg/day dose of aspirin compared with an 81-mg/day dose. An enteric-coated preparation delayed the time of response to an 81-mg/day dose. These results suggest that aspirin dose and preparation may be important mediators of the antiplatelet effects of aspirin in some patients.