Aspirin has been shown to reduce the risks of heart attack and stroke. Aspirin and other non-steroidal inflammatory drugs work by inhibiting the actions of an enzyme in platelets known as COX-1. Aspirin, however, is unique in that it irreversibly inhibits COX-1 production in platelets, whereas other NSAIDs have only a temporary inhibitory effect. Thus among the NSAIDs, aspirin alone is thought to possess cardioprotective effects.
Aspirin and the other NSAIDs bind to the same portion of the COX-1 enzyme. Because many patients are treated concomitantly with both aspirin and other NSAIDs, it was of interest to determine whether such a regimen would negate the beneficial effects of aspirin through competitive inhibition. That is, the NSAID might block aspirin from interacting with COX-1. In this study, Catella-Lawson et al (N Engl J Med. 2001 Dec 20;345(25):1844-6) investigated this potential interaction between aspirin and commonly prescribed arthritis therapies.
Methods:
Volunteers were administered one of the following regimens for six days: aspirin (81 mg) followed by ibuprofen (400 mg) two hours later and the same medications in the reverse order; aspirin followed by acetaminophen (1000 mg) two hours later and the same medications in the reverse order; aspirin followed by the COX-2 inhibitor rofecoxib (25 mg every morning) two hours later and the same medications in the reverse order; enteric-coated aspirin followed by ibuprofen (400 mg three times a day) two hours later; and enteric-coated aspirin followed by delayed-release diclofenac (75 mg twice a day) two hours later.
Results:
The concomitant administration of acetaminophen and diclofenac did not affect the effects of aspirin on COX-1 inhibition and platelet aggregation. As expected, the COX-2 inhibitor rofecoxib also did not affect the pharmacodynamics of aspirin. COX-2 inhibitors bind to a pocket on the COX-2 enzyme that is not present on the COX-1 enzyme. However, treatment with ibuprofen either as a single dose or as multiple daily doses inhibited the aggregation of platelets and COX-1 inhibition by aspirin. Acetaminophen was found to be a very weak COX-1 inhibitor and according to the authors “it is perhaps not surprising that acetaminophen also fails to modify the antiplatelet action of aspirin.” That diclofenac did not negate the effects of aspirin while ibuprofen did is somewhat surprising. This may be due to the “lower potency and shorter duration of action of the diclofenac regimen.” The authors speculate that another NSAID, indomethacin, may competitively inhibit the cardioprotective effects of aspirin to a degree similar to ibuprofen.
Conclusions:
Ibuprofen may limit the cardioprotective effects of aspirin. This may extend to other NSAIDs as well. Diclofenac, acetaminophen and rofecoxib have very little modulating effect on the cardioprotective effects of aspirin.
