Incomplete Thromboxane Inhibition with 100 mg of Intravenous Acetylsalicylic Acid in Patients with Acute ST Elevation Myocardial Infarction

Background: Acetylsalicylic acid (ASA) is now a standard treatment of acute myocardial infarction (AMI). ASA inhibits thromboxane A2 (TXA2) 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 TXA2 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 TXA2 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-TXB2 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 TXB2 after 30, 60 and 180 min following ASA injection compared to placebo, but in none of the patients was complete inhibition of TXA2 production achieved. No significant change in bleeding time could be demonstrated. Conclusion: Intravenous ASA in a dosage of 100 mg did not completely prevent TXA2 production in AMI patients treated with streptokinase. This may be due to synthesis of TXA2 by the inducible COX-2 enzyme and/or to a transcellular metabolism in platelets of prostanoids generated by endothelial cells.