Certain Painkillers May Negate Heart Benefits of HRT

Some nonsteroidal anti-inflammatory painkillers are focus of new study

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HealthDay Reporter

WEDNESDAY, May 23, 2007 (HealthDay News) -- Women who take a certain type of nonsteroidal anti-inflammatory painkiller may cancel out any benefit their heart gets from also taking hormone replacement therapy, a new study suggests.

But the findings shouldn't cause women to change their medication practices -- at least not yet, the study authors emphasize.

"This isn't a message that women who happen to be taking hormone replacement therapy and NSAIDs [nonsteroidal anti-inflammatory drugs] are headed for disaster," said senior author Dr. Garret A. FitzGerald, a professor of medicine and pharmacology at the University of Pennsylvania Institute for Translational Medicine and Therapeutics. "This shouldn't be a basis for clinical judgment but a stimulus for people to actually do research and address the question more comprehensively."

The study, published this week in the journal PLoS Medicine, brings together two of the more controversial issues in medicine today.

Hormone replacement therapy (HRT) had long been thought to prevent heart disease in postmenopausal women. The results of the landmark Women's Health Initiative (WHI) study, however, seemed to prove that not to be the case.

However, a more recent sub-analysis of data from the WHI found that hormone replacement therapy may help protect the hearts of women who start taking the hormones closer to the time menopause starts.

"The whole issue of whether there is a protective effect has been World War III," FitzGerald said. "But a recent paper suggested that what really matters is when you start taking HRT."

Dr. Suzanne Steinbaum, director of women and heart disease at Lenox Hill Hospital in New York City, added: "They (the researchers behind this week's study) studied two of the most controversial medications and studied them both together. It's a precocious study."

In the Women's Health Initiative study, a subgroup of NSAIDs known as cox-2 inhibitors were found to increase the risk of cardiovascular problems. As a result, the cox-2 inhibitors Vioxx and Bextra were withdrawn from the market.

When the cox-2 enzyme is inhibited, production of a molecule called prostacyclin is prevented. Prostacyclin, in turn, helps prevent blood clots. "The hazards of NSAIDs derive from their ability to inhibit cox-2-dependent prostacyclin," FitzGerald said.

The hormone estrogen acts to increase production of prostacyclin. This raises the possibility that lack of a heart-protective effect from estrogen may sometimes be due to the counter effect of a NSAID.

The researchers analyzed medical records for 1,673 British women aged 50 to 84 who had had heart attacks or who had died from coronary heart disease. These were compared with the medical records of 7,005 women who served as controls.

Women who were taking hormone replacement therapy had a 22 percent lower chance of having a heart attack compared with women who were not using hormones.

But women who were taking traditional NSAIDs such as ibuprofen (Motrin, Advil and others), naproxen (Aleve, Naprosyn and others) and diclofenac while they were taking hormones had a higher risk of heart attack.

"It looks pretty striking that the protective effect is converted into a hazard," FitzGerald said. "Certainly, the protection goes away if you happen to have NSAIDs on board."

As the authors themselves point out, the study suffers somewhat from being a so-called observational one, rather than a randomized, controlled study, considered the gold standard in medical research.

"The statistics here are a little bit in question, and this type of study doesn't have any control over people who could have been getting medications over-the-counter as well," said Robert Stanberry, assistant professor of pharmacy practice at Texas A&M Health Science Center Irma Lerma Rangel College of Pharmacy. "It's an interesting thought, and I think the authors are right. They need to do more studies," he added.

While the jury is still out on hormone replacement therapy and, perhaps, on traditional NSAIDs, the drawbacks of the newer cox-2 inhibitors are more well-known.

"We don't really know exactly if there's a benefit to HRT that's going to counteract the NSAIDs, but we do know that cox-2 inhibitors are really a group of medications that should not be taken regularly on a long-term basis for pain management, because they increase the incidence of heart disease. And we shouldn't rely on other types of medications to allow us to take these medications," Steinbaum said.

More information

For more on hormone therapy, visit the Women's Health Initiative site.

SOURCES: Garret A. FitzGerald, M.D., professor of medicine and pharmacology, University of Pennsylvania, Institute for Translational Medicine and Therapeutics, Philadelphia; Robert Stanberry, J.D., Pharm.D., assistant professor of pharmacy practice, Texas A&M Health Science Center Irma Lerma Rangel College of Pharmacy at Kingsville; Suzanne Steinbaum, M.D., director of women and heart disease, Lenox Hill Hospital, New York City; May 21, 2007, PLoS Medicine

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