PB0338 - The ideal acetylsalicylic acid (ASA) dose to combine with P2Y12 inhibitors: a volunteer study

Background: The ideal dose, or if any, of acetylsalicylic acid (aspirin, ASA) to use in combination with P2Y12 inhibitors in atherothrombotic disease is not known. Previous studies have demonstrated that P2Y12 inhibitors are more potent when ASA-inhibited prostacyclin (PGI2) is present. Thus, a dose of ASA that blocks PGI2 production decreases the efficacy of P2Y12 inhibitors.

Aims: We sought to determine if there is an ASA dose that does not inhibit PGI2 production, and whether this dose varies in health volunteers.

Methods: Consenting healthy volunteers (8 males and 8 females), on no antiplatelets, received blinded capsules of one of four ASA doses (i:20 mg every other day, ii:20 mg daily, iii:20 mg twice a day or iv:81 mg a day) for 14 days, then with a 14-day break, four times. Thus 16 cycles each. Blood was taken before (D0) and after (D14) each ASA cycle for arachidonic acid Multiplate Aggregometry and qualification by ELISA of serum thromboxane B2 (measures of thromboxane), and plasma 6-keto-PGF1α levels (metabolite of PGI2).

Results: Coefficient of variation of D0 values of the tests were 35%, 100% and 35% respectively. Relative to median D0 levels, all tests showed a dose response, but plasma 6-keto-PGF1α levels plateaued at the 20 mg every other day dose. Only 4 subjects (2 male, 2 female) preserved plasma 6-keto-PGF1α levels and inhibited serum thromboxane B2 levels at the 20 mg every other day dose.

Conclusion(s): In most healthy adults, the ideal ASA dose to combine with P2Y12 inhibitors is less than 20 mg every other day or none. However, in four of 16 volunteers, an ASA dose of 20 mg every other day preserved PGI2 production and would be predicted to add to the antithrombotic effect of P2Y12 inhibitors. This suggests that when used with P2Y12 inhibitors, personalized ASA dosing might have a role.