Naproxen linked to heart attack risk for older women

"That is counter to the medical community's perception of NSAIDs, in which most people believe naproxen to be safer," says Anthony Bavry. "Our study showed naproxen was not safer—it was actually harmful." (Credit: iStockphoto)

Regular use of the painkiller naproxen may increase the risk of stroke, heart attack, and even death in postmenopausal women, new research shows.

A non-steroidal anti-inflammatory drug (NSAID), naproxen is the active ingredient in medications such as Aleve. Regular use is defined as at least twice per week for the previous two weeks.

“That is counter to the medical community’s perception of NSAIDs, in which most people believe naproxen to be safer,” says Anthony Bavry, associate professor of medicine at University of Florida. “Our study showed naproxen was not safer—it was actually harmful.”

For the study, published in the journal Circulation: Cardiovascular Quality and Outcomes, researchers combed through data from more than 160,000 postmenopausal women who were surveyed as part of the Women’s Health Initiative—a 15-year research study funded by the National Institutes of Health.

Of these women, 53,142 regularly used NSAIDs. Even after controlling for obesity, hypertension, diabetes, use of aspirin, and other health factors, the researchers found the increased risk for heart attack, stroke, or death among the women who used certain types of NSAIDs.

Naproxen vs. ibuprofen

Marian Limacher, professor of medicine, emphasizes that the study was observational in nature, which helped find associations between use of NSAIDs and cardiovascular impacts.


“When we study agents such as aspirin, we have found differential effects in men and women,” she says. “Men had reduction in heart attack, and older women had a reduction in stroke but not heart attack, which is part of the reason those of us studying women feel we really need to have adequate information on commonly used drugs for both men and women.”

NSAIDs include over-the-counter medications such as naproxen and ibuprofen as well as prescription drugs such as rofecoxib, commercially branded as Vioxx, and celecoxib, branded as Celebrex. Because of its association with increased risk of heart attack or stroke, Vioxx was taken off the market in 2004.

The study’s main finding confirmed that the regular use of any NSAID was associated with harm such as digestive bleeding. Although it found for the first time that the risk of heart attack, stroke, or death was associated with the use of naproxen, the study found no cardiovascular or stroke harm associated with ibuprofen.

What’s in your medicine cabinet?

NSAIDs work by inhibiting two enzymes responsible for inflammation, called cox-1 and cox-2. They also can cause bleeding in the stomach and digestive tract. NSAIDs that target just the cox-2 enzyme, which is present mainly at the site of inflammation, are designed to prevent bleeding in the digestive tract, Bavry says.

However, previous studies showed that NSAIDs that solely target the cox-2 enzyme, which include Vioxx and Celebrex, have been associated with adverse cardiovascular events such as heart attack or stroke. Bavry thinks the culprit in naproxen is also cox-2 inhibition.

“People will have to think about what they have in their own medicine cabinet,” Bavry says. “Do they have naproxen, ibuprofen, or something else?”

The study looked only at the association between cardiovascular events and use of NSAIDs—not the effects of NSAIDs on the kidneys, for example.

“We would encourage patients to use medications for as short a time as they need, and to be sure they follow up with their physicians regularly to monitor for effects on the kidneys and potentially for risk for heart disease,” Limacher says.

Source: University of Florida