Ibuprofen Can Reduce Aspirin’s Protective Effect Against Heart Attacks and Strokes

The anti-blood clotting benefits that people get from low-dose aspirin may be offset by ibuprofen (MOTRIN, ADVIL). In fact, studies suggest that patients on low-dose aspirin who regularly use non-steroidal anti-inflammatory drugs (NSAIDs), especially well documented for ibuprofen, are at greater risk of heart attacks and other cardiovascular events than those taking aspirin alone.

Tens of millions of people take low-dose aspirin to prevent blood clots and protect against heart attacks or strokes because aspirin reduces the ability of platelets – little particles in the blood that prevent bleeding by forming clusters to plug up leaks in blood vessels – to clump together. In September 2006, the Food and Drug Administration (FDA) issued an FDA Safety Alert warning that ibuprofen can inhibit the ability of low-dose aspirin to reduce the function of platelets.

The FDA warning was largely based on studies of platelet function. In 2001, a study in The New England Journal of Medicine had shown that regular use of ibuprofen inhibited the anti-platelet effect of low-dose aspirin. Subsequent studies in healthy subjects and patients confirmed that ibuprofen interfered with the protective inhibitory effect of aspirin on platelet function. In fact, older epidemiological studies had suggested that patients on low-dose aspirin who regularly used NSAIDs, such as ibuprofen, had a greater risk of heart attacks and other cardiovascular events than those taking aspirin alone.

Complicating these studies is the fact that many NSAIDs alone are associated with increased risk of heart attacks, are also known to increase blood pressure in patients who already have high blood pressure and worsen congestive heart failure. So obviously, for a number of reasons, people with cardiovascular disease should only take NSAIDs if they are absolutely necessary.

What do newer studies show?

One very recent large randomized, controlled study involving more than 18,000 patients assessed the relative effects of the regular use of ibuprofen or naproxen (ALEVE, ANAPROX, NAPROSYN) on the risk of cardiovascular events in osteoarthritis patients, half of whom were already receiving low-dose aspirin. In this study, more people taking ibuprofen and aspirin experienced heart attacks, strokes or other cardiovascular deaths than those taking naproxen and aspirin.

Another recent study described the ibuprofen-aspirin interaction in both healthy subjects and stroke patients, the latter group all receiving low-dose aspirin to prevent additional strokes. In healthy subjects, ibuprofen taken two hours before aspirin completely blocked the ability of aspirin to inhibit platelet function. The patients who had previously had a stroke did not experience the desired effect of aspirin (the inhibition of platelet function) while also taking ibuprofen. In addition, after the ibuprofen was discontinued, all of the stroke patients experienced aspirin’s anti-clotting benefits.

Is the amount of ibuprofen used important?

Yes. Ibuprofen is eliminated from the body quickly and can only interact in that period, so limited use is not likely to be a problem. This means that an isolated dose of ibuprofen would interfere with aspirin only for about six hours in most people. So occasional use of ibuprofen – say two days a week or less – seems much less likely to interfere with the effectiveness of low-dose aspirin. This means that patients who take ibuprofen occasionally for acute pain are probably at low risk for this interaction.

On the other hand, patients who regularly take full doses of ibuprofen throughout the day will usually have enough ibuprofen in their body to interfere with low-dose aspirin no matter when the aspirin is taken. In one study, aspirin failed to inhibit platelet function in subjects who took 400 mg (two over-the-counter tablets) of ibuprofen three times daily.

Do any NSAIDs other than ibuprofen also inhibit aspirin?

As mentioned above, some evidence suggests that ibuprofen is much more likely than naproxen to interfere with the effectiveness of low-dose aspirin. Other studies of patients on low-dose aspirin comparing the effect of various NSAIDs such as sulindac (CLINORIL), meloxicam (MOBIC), diclofenac (VOLTAREN) and indomethacin (INDOCIN) also suggest that they may be less likely to interact with aspirin than ibuprofen. Nonetheless, definitive randomized trials on these other NSAIDs are needed to answer this question.

Naproxen affects platelet function in a manner similar to that of aspirin, so theoretically a person chronically taking full, regular doses of naproxen (e.g., 500 mg twice daily) would experience a beneficial effect on platelets similar to aspirin. Unfortunately, this beneficial effect has not been adequately documented and, in any case most people probably do not take naproxen regularly enough to provide an adequate effect on platelets.

Studies clearly show that the COX-2 inhibitors such as celecoxib (CELEBREX) do not interfere with the anti-platelet effect of low-dose aspirin. However, celecoxib is considerably more expensive than ibuprofen or naproxen and there is growing evidence about the ability of COX-2 inhibitors to increase the risk of cardiovascular events. For these reasons, we continue to recommend against the use of CELEBREX, even if it does have certain advantages from a drug interaction perspective.

How can the aspirin-ibuprofen interaction be avoided?

There are three ways to avoid interactions between aspirin and ibuprofen:

1. Consider using acetaminophen (TYLENOL), which is not an NSAID. In patients with mild-to-moderate joint pain, acetaminophen has been shown to be as effective as NSAIDs, but it does not interfere with the protective effects of low-dose aspirin. The American College of Rheumatology, the American Geriatric Society and the American Pain Society have all adopted guidelines identifying acetaminophen as a first-line drug choice for mild-to-moderate arthritis pain, given its efficacy, mild side effects, over-the-counter availability and low cost.
   
2. Because naproxen may be less likely than ibuprofen to interact with low-dose aspirin, consider using naproxen in place of ibuprofen because, based on evidence available at this point, it appears to be less likely than ibuprofen to interfere with the beneficial effects of low-dose aspirin.
   
3. If ibuprofen is used with low-dose aspirin, it should only be used occasionally, at most once or twice a week. Patients should take the aspirin at least an hour or two before or 12 hours after taking the ibuprofen.