Effective long-term inhibition of thromboxane production but not of serotonin release in patients with coronary heart disease by 30 mg/d acetylsalicylic acid dosage.
Efficacy of aspirin (Acetylsalicylic acid, ASA) antiaggregatory prevention was demonstrated in a series of clinical trials. The recommended ASA doses decreased gradually and doses 50-30 mg ASA/d are intensively studied at the present time. A group of 42 patients with coronary heart disease was evaluated: (1) Basal TXB2 production during spontaneous blood clotting was 360 +/- 37.6 ng/ml; (2) Two initial doses were tested: while 200 mg ASA inhibited, during spontaneous blood clotting, median TXB2 production by 99.9% (serum TXB2 concentration 1.35 ng/ml), 30 mg ASA median inhibition was just 42.0% (serum TXB2 151 ng/ml); (3) 30 mg ASA/d maintenance dose was evaluated for 3 months. The median TXB2 production inhibition was 98.5% (serum TXB2 3.75 ng/ml, first month) and 94.0% (serum TXB2 14.2 ng/ml, third month); (4) Four patients did not respond sufficiently, because of noncompliance verified by the determination of salicyluric acid urinary excretion, the lower limit of excretion being <3 micromol/2 h; (5) Both initial and maintenance ASA dose decreased metabolic TXA2 endproducts in urine; (6) 5HT platelet release did not decrease; (7) Potential changes of 5HT metabolic elimination were excluded by the simultaneous determination of 5-hydroxyindoleacetic acid (5HIAA). In conclusion, 200 mg initial dose and 30 mg ASA/d maintenance dose are suggested to be maximally inhibitory for TXB2 production without influence on 5HT release.
Gajdos
M
M
Institute of Preventive and Clinical Medicine, Department of Pharmacotherapy, Bratislava, Slovak Republic.
Spustová
V
V
Sebeková
K
K
Krivosiková
Z
Z
Dzúrik
R
R
D001241:Aspirin / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects; D003327:Coronary Disease / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D017202:Myocardial Ischemia / Q000517:prevention & control; D012701:Serotonin / Q000378:metabolism*; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors* / Q000652:urine; D013929:Thromboxane B2 / Q000378:metabolism
D012701:Serotonin; D013929:Thromboxane B2; D013928:Thromboxane A2; D001241:Aspirin