If the first thing you do when you’re hurting is reach for aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn) or a similar nonsteroidal anti-inflammatory drug (NSAID), stop, look and listen. I’ve got more crucial news about how and which of these pain killers do a number on your cardiovascular system.

Several studies have already suggested that these drugs, particularly celecoxib (Celebrex), can threaten heart health when taken often over a long period of time. Now findings from a very large study—part of the Women’s Health Initiative (WHI), a 15-year research study funded by the National Institutes of Health—not only clarify which NSAIDs are most dastardly for heart health, they pinpoint the reason why.

Although this study focused on women, it applies to men as well in light of other large, recent studies that included men and women and found similar results, including a Dutch study on NSAIDs and atrial fibrillation in older adults.


The WHI study evaluated NSAID use and cardiovascular health over an 11-year period in 161,801 postmenopausal women between the ages of 50 and 79. A wide range of NSAIDs were used among this very large study population.

The researchers mainly wanted to confirm whether NSAIDs that primarily worked by inhibiting an inflammatory enzyme called cyclooxygenase 2 (COX-2) were more detrimental to heart health than other NSAIDs. If you weren’t already aware, all NSAIDs actually work by inhibiting cyclooxygenases—either COX-2 (such as Celebrex, the only COX-2 inhibitor currently available in the United States) or COX-1 (aspirin) or both (most every other NSAID on the shelf). NSAIDs that target both are referred to as nonselective NSAIDs because they do not “select” one cyclooxygenase over another. However, some do focus more on COX-1 inhibition (ibuprofen, for example) or COX-2 inhibition (naproxen, for example).

The researchers did indeed find that COX-2 inhibitors (Celebrex and other drugs that were once available in the United States, such as Vioxx) were associated with an increased risk of strokes and heart attacks in postmenopausal women who used them two or more times per week for at least two weeks. No surprise here—selective COX-2 inhibitors are infamous for their negative effects on heart health. But they also found that nonselective NSAIDs that focused more on COX-2 than COX-1 inhibition were just as dangerous when used two or more times per week for at least two weeks. That’s amazing and alarming, considering that we usually don’t think that taking an NSAID twice a week for more than a week is such a big deal.

And this finding puts naproxen, a popular OTC drugstore painkiller, squarely in the “doghouse” as far as cardiovascular safety goes.

In particular, regular use of Celebrex was associated with a higher risk of stroke…and regular use of nonselective NSAIDs that leaned toward COX-2 inhibition (such as naproxen) were associated with higher risk of heart attack.

Meanwhile, regular use of ibuprofen was not associated with increased cardiovascular risk.


The researchers’ final word was that postmenopausal women should opt for aspirin or ibuprofen instead of naproxen or celecoxib for pain relief. But the findings are probably relevant to anyone who uses NSAIDs, including men and younger women, because, as mentioned, studies are accumulating about the risks of NSAIDs in various population groups.

One thing to keep in mind, though, is that regular use of aspirin or ibuprofen, even though they came out looking best in this particular study, has other potential pitfalls—stomach ulcers, for one. And aspirin is a blood thinner, as you know, and so must be used with caution. Considering that dependence on NSAIDs of any kind has drawbacks, why not look into alternatives for chronic pain relief? Check out Bottom Line’s Guide to Drug-Free Back Pain Relief and Guide to Joint Pain Relief for solutions.