Do NSAIDs Impair the Cardioprotective Effects of Aspirin?

Much recent attention, in boththe medical literature and thelay press, has focused onwhether ibuprofen (eg, Advil, Motrin)can interfere with the cardioprotectiveeffects of low-dose aspirin. The discussionstarted following publication ofthe results of a study by Catella-Lawsonet al in the New England Journal ofMedicine in 2001, showing that regularuse of ibuprofen inhibited theantiplatelet effect of low-dose aspirin.¹Numerous articles have followed, butmany unanswered questions remain.

Is the Interaction ClinicallyImportant?

Following the Catella-Lawson article,several epidemiologic studies haveinvestigated patient outcomes withlow-dose aspirin alone versus low-doseaspirin plus ibuprofen or other nonsteroidalanti-inflammatory drugs(NSAIDs). In general, the epidemiologicstudies found a reduced ability ofaspirin to protect against cardiovasculardisease, but none of the studies canbe considered definitive. The most onecan say at this point is that ibuprofenmay reduce aspirin efficacy, but morestudy is needed.^2-5

Is the Dose of IbuprofenImportant?

The dose of ibuprofen appears to beimportant. The original study byCatella-Lawson and colleagues foundan inhibition of the aspirin antiplateleteffect with ibuprofen 400 mgtid, but not when ibuprofen was givenonce a day and 2 hours after theaspirin. So, at least as far as inhibitionof the antiplatelet effect of aspirin isconcerned, occasional doses of ibuprofendo not seem to be a problem.

Could the Interaction BeOvercome by Increasing theAspirin Dose?

It is not known whether increasingthe aspirin dose in the presence ofibuprofen would restore the antiplateleteffect of the aspirin.

Also, the current discussion involvesthe use of low-dose aspirin for the preventionof cardiovascular disease, ratherthan the use of aspirin as an analgesic.Combining long-term analgesic dosesof aspirin with NSAIDs presents otherissues, of course, such as a possibleincrease in gastrointestinal toxicity.

How About NSAIDs Other ThanIbuprofen?

Catella-Lawson and associatesfound that diclofenac (Cataflam,Voltaren) 75 mg bid did not influencethe antiplatelet effects of aspirin.Some of the epidemiologic studiesalso suggest that ibuprofen may bemore likely than other NSAIDs toinhibit the efficacy of low-doseaspirin. Although it is too early to besure, some NSAIDs may be found notto interact with aspirin.

How About COX-2 Inhibitors?

Cyclooxygenase-2 (COX-2) inhibitors—such as celecoxib (Celebrex),rofecoxib (Vioxx), and valdecoxib(Bextra)—do not affect platelet functionand do not appear to impair theantiplatelet effects of aspirin.^1,6,7 Thus,it does not appear likely that COX-2inhibitors would interfere with the cardioprotectiveeffects of aspirin.

Other Cardiovascular Effects of NSAIDs

Even if ibuprofen and other NSAIDseventually prove to have little effect on the cardioprotective effects of aspirin,they need to be used with caution in patients with certain cardiovascular diseases.For example, NSAIDs can increase blood pressure and worsen congestiveheart failure, especially in patients receiving angiotensin-convertingenzyme inhibitors or angiotensin receptor antagonists.

Recommendations

Although more study is needed to establish whether ibuprofen or otherNSAIDs inhibit the cardioprotective effects of aspirin, it would be prudentto take appropriate precautions until more data are available.

• Generally avoid the use of ibuprofen in patients on low-dose aspirin(occasional use of ibuprofen is unlikely to be a problem)
• Warn patients on low-dose aspirinto avoid OTC ibuprofen unless advised to take it by their prescriber
• If appropriate, consider the use of alternatives to ibuprofen, such asacetaminophen (eg, Tylenol), diclofenac, or COX-2 inhibitors
• If it is decided to use ibuprofen, try to avoid administering aspirin lessthan 2 hours before or 6 hours after ibuprofen

Conclusion

The preponderance of available evidence suggests that regular use ofibuprofen may inhibit the cardioprotective effects of aspirin, but more evidenceis needed to establish the clinical importance. Diclofenac and COX-2inhibitors may be less likely to interact, but little is known about others.

Drs. Horn and Hansten are both professors of pharmacy at the University of Washington School of Pharmacy. For an electronic version of this article, including references, visit www.hanstenandhorn.com.