COMPARISON OF CYCLOOXYGENASE INHIBITION WITH 2 DIFFERENT DOSES OF ENTERIC-COATED ASPIRIN IN NORMAL YOUNG AND ELDERLY SUBJECTS AND ELDERLY WITH CEREBROVASCULAR-DISEASE

There is still controversy about the optimum dose and formulation of a spirin for prophylaxis of thrombo-embolic events in patients with cere brovascular disease. Enteric coated formulations of aspirin have poten tial advantages over rapidly absorbed formulations in terms of fewer s ide effects and more selective platelet cyclooxygenase inhibition. We compared 7-day courses of 100 mg and 650 mg per day enteric coated asp irin in young, healthy subjects and in two groups of elderly subjects of 70 years and above, one group without vascular disease and the othe r with cerebrovascular disease. Prior to aspirin treatment, the elderl y with cerebrovascular disease had higher levels of the urinary thromb oxane A(2) (TXA(2)) metabolite 11-dehydro-TXB(2); the mean in the elde rly ill was 4,064 +/- 1,762 pg/mg creatinine (n = 8) compared to level s of 982 +/- 139 pg/mg creatinine (n = 17) in the young, and 1,560 +/- 380 pg/mg creatinine (n = 14) in the healthy elderly (p < 0.05 and p < 0.01, respectively). Aspirin (100 mg) inhibited serum TXB(2) generat ion in all groups, with the greatest percentage inhibition occurring i n the elderly with cerebrovascular disease. In the ill elderly serum T XB(2) was 1.9 +/- 0.05% (n = 8) of control compared to 4.2 +/- 0.6% (n = 17, p < 0.05) in the young and 9.4 +/- 3.5% (n = 14, p < 0.01) in t he healthy elderly. All young and diseased elderly subjects achieved g reater than 90% inhibition with 100 mg aspirin, but 4 of 14 healthy el derly subjects achieved less than 90% inhibition. The 650-mg dose of a spirin produced further inhibition in serum TXB(2) in the young and he althy elderly subjects and inhibited serum TXB(2) to greater than 90% of control levels in all subjects. The higher dose also produced great er reductions in 11-dehydro-TXB(2) levels, and these were statisticall y significant in the young and ill elderly. Urinary-6-keto PGF(1 alpha ) was not significantly decreased at either dose, except in the elderl y ill taking 650 mg a day in whom it was reduced to 55 +/- 18% of cont rol (n = 8, p < 0.05). Thus enteric coated aspirin at doses of 100 and 650 mg taken daily for 7 days inhibited platelet cyclooxygenase with relative sparing of endothelial cyclooxygenase. The elderly with cereb rovascular disease were more sensitive to the platelet and endothelial cyclooxygenase inhibition effects of enteric coated aspirin than the healthy elderly and healthy young groups.