Study Using Pain Reliever Aleve Suspended


12.21.2004, 10:46 AM

An Alzheimer's disease prevention trial was suspended after researchers said there were more heart attacks and strokes among patients taking naproxen, an over-the-counter pain reliever in use for 28 years and commonly known under the brand name Aleve.

The study, involving some 2,500 patients, was to test whether naproxen or Celebrex, both pain relievers, could reduce the risk of Alzheimer's disease among healthy elderly patients who were at an increased risk of the disease.

Officials at the National Institutes of Health said the study was suspended after three years when it was found that patients taking naproxen had a 50 percent greater incidence of cardiovascular events - heart attack or stroke - than patients taking placebo.

Another factor, officials said, was the announcement last week that advertising for Celebrex was being halted after a study found that high doses of the drug were associated with an increase in heart attack risk. Preliminary data from the Alzheimer's study, however, did not indicate an increased risk for heart attack or stroke for Celebrex, officials said.

Lester Crawford, acting commissioner of the Food and Drug Administration, acknowledged Tuesday that the conflicting studies are confusing and call for continued evaluation. For now, he recommended following the dosage recommendations for the drugs.

"Any drug taken long enough and at high enough dosage can cause some difficulty," Crawford said on NBC's "Today."

"It would be premature to say what we we're going to do with either one of these drugs, Celebrex or Aleve," he said. "However, we will keep all regulator options open and make some determinations as quickly as possible based on the data."

Celebrex, a prescription drug, and naproxen are both commonly used to treat the joint pain of arthritis. Naproxen has been approved for sale, first as a prescription and then as an over-the-counter drug, since 1976. Celebrex is in the same class - COX2 enzyme inhibitors - as Vioxx, an arthritis drug recently taken off the market by its manufacturer after it was linked to an increase in heart attack and stroke.

Officials acknowledged that the implications for the continued use of naproxen are not clear and will require further study.

Dr. Sandra Kweder of the FDA said the NIH study is the first to show that naproxen might increase the risk of heart attack or stroke and that the findings are "confusing." No immediate action, however, is expected toward naproxen, she said.

"We are not contemplating any specific regulatory action over the next few days," Kweder said. "We will be working with the NIH to try to understand the data better and determine what will be appropriate from there."

Patients who routinely take naproxen should follow the drug package instructions carefully, Kweder said, including the directions to not take it for more than 10 days, and to consult a doctor if pain persists.

Efforts to obtain reaction Monday night produced no answers at phone numbers for Bayer Healthcare, the maker of Aleve.

In the earlier studies of the COX2 drugs, an increase in cardiovascular events was noted only after a long-term use of the medications.

The Alzheimer's disease study was being conducted by the National Institute on Aging, an arm of the NIH. It called for 2,500 patients aged 70 or older and who had a family history of Alzheimer's, to take either Celebrex, naproxen or a placebo.

The group was divided and each division, or arm, was assigned to receive one of the drugs or placebo. The drugs were blinded, which means the patients did not know which medication they were taking, or if they were taking a placebo.

The goal was to determine if the pain-relieving drugs lowered the risk of developing Alzheimer's disease. The study started three years ago and was to continue for a few more years. Officials said the patients in the study will be monitored for developing Alzheimer's or cognitive decline, but will not be given the test drugs.

Dr. Elias A. Zerhouni, the director of the National Institutes of Health, said the study linking heart attack to Celebrex last week was a major factor in deciding to suspend the Alzheimer's study.

He said there was a question whether patients in the study would continue to take their medicine since they knew they might be taking Celebrex.

Suspending the study, Zerhouni said, "is the prudent thing to do."

John Breitner of the Veterans Affairs medical facility in Seattle and the University of Washington, an investigator in the trial, said only preliminary data is available. But he said it suggests that among the 2,500 patients in the study, about 70 suffered stroke or heart attack. There were 23 deaths. There were 50 percent more of the cardiovascular events among patients taking naproxen than among those taking placebo, he said.

In trading Tuesday, shares of Aleve's German manufacturer, Bayer AG, and Pfizer Inc., maker of Celebrex, were down. Pfizer shares have fallen more than 13 percent since the company announced Friday that a study had found that high doses of the drug were associated with an increase in heart attack risk.