Comparison of Cyclooxygenase Inhibition with Two Different Doses of Enteric Coated Aspirin in Normal Young and Elderly Subjects and Elderly with Cerebrovascular Disease

Abstract

There is still controversy about the optimum dose and formulation of aspirin for prophylaxis of thrombo-embolic events in patients with cerebrovascular disease. Enteric coated formulations of aspirin have po tential advantages over rapidly absorbed formulations in terms of fewer side effects and more selective platelet cyclooxygenase inhibition. We compared 7-day courses of 100 mg and 650 mg per day enteric coated aspirin in young, healthy subjects and in two groups of elderly sub jects of 70 years and above, one group without vascular disease and the other with cerebrovascular disease. Prior to aspirin treatment, the elderly with cerebrovascular dis ease had higher levels of the urinary thromboxane A2 (TXA2) metabolite 11-dehydro-TXB2; the mean in the el derly ill was 4,064 ± 1,762 pg/mg creatinine (n = 8) com pared to levels 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 TXB2 generation in all groups, with the greatest percentage inhibition occurring in the elderly with cerebrovascular disease. In the ill el derly serum TXB2 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 the healthy elderly. All young and diseased elderly subjects achieved greater than 90% inhibition with 100 mg aspirin, but 4 of 14 healthy elderly subjects achieved less than 90% inhibi tion. The 650-mg dose of aspirin produced further inhibi tion in serum TXB2 in the young and healthy elderly sub jects and inhibited serum TXB2 to greater than 90% of control levels in all subjects. The higher dose also pro duced greater reductions in 11-dehydro-TXB2 levels, and these were statistically significant in the young and ill elderly. Urinary-6-keto PGF1α was not significantly de creased at either dose, except in the elderly ill taking 650 mg a day in whom it was reduced to 55 ± 18% of control (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 cy clooxygenase. The elderly with cerebrovascular disease were more sensitive to the platelet and endothelial cyclo oxygenase inhibition effects of enteric coated aspirin than the healthy elderly and healthy young groups.