Acetylsalicylic acid and the balance between prostacyclin and thromboxane A2.

Arachidonic acid is metabolized in endothelial cells to antiaggregatory, vasodilatory prostacyclin (PGI2), and in platelets to aggregatory, vasoconstrictory thromboxane A2 (TxA2). The balance of these two prostanoids is supposed to be involved with thrombogenesis and atherogenesis. Acetylsalicylic acid (ASA) inhibits irreversibly the key enzyme of the synthesis of these prostanoids, i.e. cyclo-oxygenase. Platelets do not synthetize new protein, but endothelial cells do. Because of this, and certain pharmacokinetic characteristics of ASA, it should be possible to shift the balance between PGI2 and TxA2 to the dominance of the former with the proper dose of this drug. Altogether more than 50,000 subjects have volunteered for studies on the effect of ASA in the primary or secondary prevention of myocardial infarction or ischemic stroke. The results show that it is possible to reduce vascular attacks by ASA. Furthermore, ASA has also found to prevent pre-eclampsia. Conclusions on the effect of ASA on the PGI2/TxA2-balance are hampered by uncertainties concerning the measurement PGI2 and TxA2 productions in vivo. It is, however, evident that the doses of ASA used in most trials have been high enough to inhibit partly also the production of PGI2. Whether smaller doses or less frequent administration would be more efficient, remains to be studied.