Incomplete Thromboxane Inhibition with 100 mg of Intravenous Acetylsalicylic Acid in Patients with Acute ST Elevation Myocardial Infarction: A Placebo-Controlled Pilot Trial

Background: Acetylsalicylic acid (ASA) is now a standard treatment of acute myocardial infarction (AMI). ASA inhibits thromboxane A 2 (TXA 2) production by blocking the constitutive cyclooxygenase (COX)-1 enzyme, but only to a small degree the inducible COX-2. COX-2 is induced by increased concentrations of cytokines, which is related to an enhanced inflammatory response. Previously, we have found a complete inhibition of TXA 2 synthesis in healthy volunteers after intravenous administration of 50 mg of ASA. We measured in a randomized, placebo-controlled pilot trial the effect of 100 mg of ASA injected intravenously on TXA 2 synthesis in AMI patients treated with streptokinase. Methods and results: Nineteen patients with AMI treated with streptokinase were randomized to 100 mg of ASA or placebo injected intravenously. Se-TXB 2 and bleeding time were measured before and after drug administration. One hundred and eighty minutes after intravenous ASA administration, treatment with oral ASA was initiated. We found a significant decrease in serum concentrations of TXB 2 after 30, 60 and 180 min following ASA injection compared to placebo, but in none of the patients was complete inhibition of TXA 2 production achieved. No significant change in bleeding time could be demonstrated. Conclusion: Intravenous ASA in a dosage of 100 mg did not completely prevent TXA 2 production in AMI patients treated with streptokinase. This may be due to synthesis of TXA 2 by the inducible COX-2 enzyme and/or to a transcellular metabolism in platelets of prostanoids generated by endothelial cells.