The Optimal Antithrombotic Dose of Aspirin

Abstract

Clinical trials over the last decade have demonstrated that aspirin is an effective antithrombotic agent. Aspirin irreversibly inhibits the enzyme cyclo-oxygenase, which in the platelet is responsible for the production of thromboxane A 2 , a platelet-aggregating agent; and, in vascular wall cells, cyclooxygenase is responsible for the production of prostacyclin (PGI 2 ), an inhibitor of platelet aggregation. Thus, aspirin has the potential to be both antithrombotic and thrombogenic. Low doses of aspirin (325 mg or less) inhibit cyclo-oxygenase in platelets and vascular wall cells, but the inhibitory effect on platelet thromboxane A 2 synthesis is greater and lasts longer than its effect on vascular wall PGI 2 synthesis. 1 The therapeutic importance of inhibiting PGI 2 may have been overestimated in the past. Experimentally, aspirin is only thrombogenic at very high doses 2 (200 mg/kg), which far exceed the minimum dose required to inhibit PGI 2 production. This suggests that inhibition of PGI2 production may not be the