NEW YORK (Reuters Health) – Clinical doses of ibuprofen counteract aspirin's cardioprotective effects, at least in vitro, according to a report in the December 20th issue of The New England Journal of Medicine.
Dr. Garret A. FitzGerald and colleagues, of the University of Pennsylvania School of Medicine in Philadelphia, first conducted a 6-day crossover study with single daily doses of aspirin 81 mg in combination with ibuprofen 400 mg, acetaminophen 1000 mg, or rofecoxib 25 mg. Each treatment combination involved a sample of five subjects.
Measurements of serum thromboxane B-2 were used to assess platelet cyclooxygenase-1 (COX-1) activity. When aspirin was given 2 hours before ibuprofen, serum thromboxane B-2 was 98% inhibited for up to 24 hours after dosing on day 6. When dosing was reversed, with ibuprofen administered 2 hours before aspirin, inhibition was 97% at 2 hours after dosing, but had fallen to 53% by 24 hours after the final dose. Pretreatment with acetaminophen or with rofecoxib failed to alter aspirin's antiplatelet effect.
Findings were similar for platelet aggregation, which was reversibly inhibited when subjects took ibuprofen, but not acetaminophen or rofecoxib, before aspirin.
Dr. FitzGerald's team then conducted a parallel-group study, in which subjects took aspirin 2 hours before the first of three daily doses of ibuprofen or of two daily doses of delayed-release diclofenac 75 mg. The investigators found that the effects of daily low-dose aspirin on platelets were blocked by the prolonged use of three daily doses of ibuprofen, even when the aspirin was administered first. Diclofenac produced no such interaction.
In an editorial, Dr. Leslie J. Crofford describes as "interesting and important" the hypothesis of the Philadelphia group that some nonsteroidal antiinflammatory drugs (NSAIDs) could interfere with the antiplatelet effect of aspirin by occupying the hydrophobic channel of platelet COX-1.
Dr. Crofford, of the University of Michigan an Ann Arbor, notes, however, that their studies were performed ex vivo and that they tested platelet function in isolation. "In vivo and clinical studies assessing the combination of low-dose aspirin with NSAIDs, coxibs, or acetaminophen will be required to determine the cardiovascular implications of the interactions among these drugs," the commentator suggests.
Dr. Crofford concludes that if these findings are confirmed as clinically important, physicians prescribing a combination of aspirin and NSAID will need to consider their interaction.
N Engl J Med 2001;345:1809-1817, 1844-1846.
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