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Researchers Find Association Between NSAIDs and Heart Attack in Postmenopausal Women

COX-2 inhibition may be the culprit

A study conducted at the University of Florida has found that the regular use of some nonsteroidal anti-inflammatory drugs (NSAIDs) increases the risk of stroke, heart attack, or death in postmenopausal women. The study was published in Circulation: Cardiovascular Quality and Outcomes.

The researchers found that regular use of the NSAID naproxen, the active ingredient in medications such as Aleve (Bayer), is associated with a 10% increased risk of heart attack, stroke, or death in postmenopausal women, said lead author Dr. Anthony Bavry. Regular use was defined as at least twice per week for the previous 2 weeks.

“That is counter to the medical community’s perception of NSAIDs, in which most people believe naproxen to be safer,” Bavry said. “Our study showed naproxen was not safer — it was actually harmful.”

Bavry and his colleagues looked at 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, the 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.

One of the study’s co-authors, Dr. Marian Limacher, emphasized that the study was observational in nature, which helped the researchers find associations between the use of NSAIDs and cardiovascular effects. Limacher also noted that this was the first study of its size to examine the effects of regular NSAID use in women.

NSAIDs include over-the-counter medications, such as naproxen and ibuprofen, as well as prescription drugs, such as Vioxx (rofecoxib, Merck) and Celebrex (celecoxib, Pfizer). Because of its association with an 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 gastrointestinal bleeding. Although the study found for the first time that a risk of heart attack, stroke, or death was associated with the use of naproxen, it found no cardiovascular or stroke harm linked to ibuprofen.

NSAIDs work by inhibiting two enzymes responsible for inflammation — cyclooxygenase-1 (COX-1) and COX-2. The drugs also can cause bleeding in the stomach and digestive tract. NSAIDs that target only the COX-2 enzyme, which is present mainly at the site of inflammation, are designed to prevent bleeding in the digestive tract, Bavry said.

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

The study looked only at the association between cardiovascular events and the 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 said.

Source: University of Florida; July 9, 2014.

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