ASPIRIN THERAPY - OPTIMIZED PLATELET INHIBITION WITH DIFFERENT LOADING AND MAINTENANCE DOSES

Inhibition of cyclooxygenase by aspirin has been shown to be beneficial in clinical situations such as acute myocardial infarction or unstable angina. The precise effect of various doses of aspirin on acute and long-term inhibition of platelet aggregation and thromboxane synthesis remains unclear. In this study we evaluated the effect of oral aspirin (0, 40, 100, 300, or 500 mg) as the initial loading dose in combination with different maintenance doses of aspirin (0, 40, or 100 mg/day) for 14 days on platelet function in healthy men. Bleeding time 2 or 24 hours after the first aspirin administration was significantly increased for 300 and 500 mg aspirin (p < 0.01). Two hours after the first administration of 100, 300, and 500 mg aspirin, a significant inhibition of collagen-induced platelet aggregation (ED(50) collagen: from 3 +/- 1 to 17 +/- 2, 24 +/- 3, 22 +/- 3 mu g/ml, respectively) was seen. At the same time serum thromboxane B-2 synthesis was inhibited by more than 99% with 300 and 500 mg aspirin. At the end of the 14-day observation period, bleeding time was significantly prolonged for the different combinations of aspirin doses compared with initial values (p < 0.01). Collagen-induced platelet aggregation and serum thromboxane B-2 synthesis were significantly inhibited for all aspirin combinations tested at 14 days (p < 0.05). The 40/40 mg aspirin combination was less effective, because it reached its maximal effect very late at day 7 of the observation period compared with the other combinations. The results of our study indicate that a loading dose of 300 mg aspirin in combination with 40 mg as a maintenance dose resulted in sufficient inhibition of platelet aggregation and of thromboxane synthesis during the 14-day observation period.