Amount of Platelet Inhibition Produced When Initiating Aspirin Therapy: Comparison of Two Doses 81 Vs. 325

Patients with occlusive arterial disease are commonly treated with different daily doses of aspirin usually either 81 or 325mg. This treatment practice continues despite studies showing equal protection from future vascular events with daily aspirin doses that exceed 81mg. We evaluated the hypothesis that the amount of platelet inhibition observed 96 hours after initiating aspirin therapy with 3 daily doses of 81mg would be equivalent to that observed using a dose of 325mg.

The amount of platelet inhibition produced when initiating daily aspirin therapy was evaluated using the slope of the platelet prostaglandin agonist (PPA) stimulated light aggregometry curve at 4 time points: time 0 before the first dose, 2 hours after the first dose, 24 hours after the first dose (just before the second dose) and 96 hours after the first dose (24 hours after the 3^rd dose). After a 7 day wash out period, during which subjects were instructed not to take aspirin or other NSAIDs, the subjects repeated the study using a 325mg aspirin dose. Because of the large variation in reactivity of platelets among people, each normal subject served as their own control and the results were evaluated using a paired “t” test. We plan to have studied a minimum of 12 normal subjects by the time of the ASH meeting.

To date 6 normal subjects were studied. 96 hours after initiating aspirin therapy, 24 hours after the 3^rd aspirin dose, there was no difference between the PPA slopes observed for the 81mg=36 and the 325mg=28 (p=.28). Immediate platelet inhibition observed in the 24 hours after initiating aspirin therapy was far greater with the 325mg than the 81mg dose. Two hours after the 81mg dose the PPA slope was 77 compared to the 325mg slope of 12 (p=.000). Similarly, the slopes 24 hours after initiating aspirin were 68 for the 81mg dose and 35 for the 325mg dose (p=.006). The time 0 slopes were also statistically different 81mg=91 and 325=78 (p=.024).

1. Initiation of aspirin therapy with a dose of 325mg dose produces a more immediate inhibition of platelet function with maximal platelet inhibition observed 2 hours after the first dose. 2. Platelet inhibition with an aspirin dose of 81mg occurs more gradually with maximal platelet inhibition observed 24 hours after the 3^rd dose at 96 hours. 3. Whether daily aspirin therapy is initiated with a daily dose of 81mg or 325mg, the amount of platelet inhibition observed 96 hours after starting aspirin therapy, 24 hours after the 3^rd dose, is equivalent.

This data supports the clinical observations that protection from future vascular events is equivalent with either 81 or 325mg daily dosing and suggests that the current practice of increasing the dose of aspirin in patients who experience a subsequent event may not be beneficial.

No relevant conflicts of interest to declare.