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.


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.


CONCLUSIONS
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.
Ziegler
B K
BK
Department of Medicine and Cardiology, Aarhus Amtssygehus, University Hospital of Aarhus, Aarhus C 8000, Denmark. b.ziegler@dadlnet.dk
Kristensen
S D
SD
Vissinger
H
H
Jensen
H K
HK
Nielsen
H K
HK
Husted
S E
SE
D000368:Aged; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000201:enzymology; D010865:Pilot Projects; D013300:Streptokinase / Q000008:administration & dosage; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000097:blood; D013929:Thromboxane B2 / Q000037:antagonists & inhibitors / Q000097:blood; D013931:Thromboxanes / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000097:blood
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D013931:Thromboxanes; D013929:Thromboxane B2; D013928:Thromboxane A2; D013300:Streptokinase; D001241:Aspirin