Do painkiller risks outweigh rewards?

U. FLORIDA (US) — A new study finds a doubling of deaths among people who have both hypertension and coronary artery disease and have used NSAIDs to treat chronic pain.

The findings, published in The American Journal of Medicine, raise further concerns about the potential risks of nonsteroidal anti-inflammatory drugs such as ibuprofen, naxopren, and celecoxib.

“It does strengthen our practice recommendations,” says lead author Anthony A. Bavry, assistant professor of cardiovascular medicine at the University of Florida.

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The use of NSAIDs among the elderly and after heart attacks is already discouraged, on the basis of several studies showing that the drugs are linked with a higher risk of stroke and heart attack, but the new study advises patients to talk to their doctors before stopping use of prescribed treatments.

“It’s a tricky issue, because NSAIDs are useful for relieving pain, and that is much of what we do in medicine—alleviate pain and suffering,” says Deepak L. Bhatt, associate professor of medicine at Harvard University, who recently published his own findings that NSAIDs are linked to a higher risk of stroke, and was not involved in the current study.

“Unfortunately, most medications have some potential side effects, and it’s important to know what those might be.”

Patients who have both high blood pressure and coronary artery disease are generally put on aspirin, a unique type of NSAID, to reduce their risk of a heart attack.

Physicians are concerned that giving those patients other NSAIDs for pain relief could cancel out aspirin’s beneficial effects and raise the risk of negative cardiovascular effects.

Using INVEST study data from 882 chronic NSAID users and almost 22,000 intermittent or nonusers, researchers looked at patients who reported using NSAIDs over an average of about three years, to see whether there was an increase in adverse events or cardiovascular-related death compared with patients who did not use those pain medicines long term.

The risk of death from cardiovascular causes was 2.3 times higher among patients who chronically used the drugs than among other patients.

NSAIDs are thought to act in a variety of ways to increase cardiovascular risk—they are believed to prevent aspirin’s protective anti-clotting effect by blocking it from binding properly to platelets in the blood.

Some NSAIDs might also increase bleeding risk. NSAIDs also raise blood pressure, thus potentially raising the risk of heart attack and stroke. Some NSAIDs have already been removed from the market because of concerns about an elevated risk of heart attack and stroke.

While randomized clinical trials are still needed to definitively show a link between NSAIDS and cardiovascular effects, the current study is only the latest in a growing body of research that strongly suggests an association.

“There have been enough studies now that it certainly raises suspicion,” Bhatt says. “The question that’s still open is, is it all NSAIDs, or are some worse than others?”

The INVEST study was funded by Abbott Laboratories and the University of Florida Opportunity Fund. The National Institutes of Health also provided grant support for several of the researchers. Members of the research team have also received grant funding from, or served as consultants for, a number of pharmaceutical companies.

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