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)) produc tion by blocking the constitutive cyclooxygenase (COX)-1 enzyme, but only t o a small degree the inducible COX-2. COX-2 is induced by increased concent rations of cytokines, which is related to an enhanced inflammatory response . Previously, we have found a complete inhibition of TXA(2) synthesis in he althy volunteers after intravenous administration of 50 mg of ASA. We measu red in a randomized, placebo-controlled pilot trial the effect of 100 mg of ASA injected intravenously on TXA(2) synthesis in AMI patients treated wit h streptokinase. Methods and results: Nineteen patients with AMI treated wi th streptokinase were randomized to 100 mg of ASA or placebo injected intra venously. Se-TXB2 and bleeding time were measured before and after drug adm inistration. One hundred and eighty minutes after intravenous ASA administr ation, treatment with oral ASA was initiated. We found a significant decrea se in serum concentrations of TXB2 after 30, 60 and 180 min following ASA i njection compared to placebo, but in none of the patients was complete inhi bition of TXA(2) production achieved. No significant change in bleeding tim e could be demonstrated. Conclusion: Intravenous ASA in a dosage of 100 mg did not completely prevent TXA(2) production in AMI patients treated with s treptokinase. 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 ge nerated by endothelial cells. (C) 2001 Elsevier Science Ltd. All rights res erved.