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KEYCODE BAYER #174

Monday, December 20, 2004

Bayer´s Naproxen increases heart attacks

WASHINGTON -- 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.

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 is not clear and will require further study.

Dr. Sandra Kweder of the Food and Drug Administration 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," said Kweder. "We will be working with the NIH to try to understand the data better and determine what will be appropriate from there."

She said patients who routinely take naproxen should follow the drug package instructions carefully, 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. (By PAUL RECER, AP SCIENCE WRITER )

Nov. 17, 2006

Study: Naproxen Painkillers May Pose Heart Danger

WASHINGTON -- Researchers looking at the safety of various arthritis and headache remedies said on Thursday they had found some more evidence that the popular analgesic naproxen may cause heart problems.
The researchers themselves cautioned about reading too much into their findings, and outside experts discounted them.
Nonetheless, the researchers said they thought it was important to present their evidence to help experts sort out what the real dangers are.
The issue is important because companies have been forced to withdraw several drugs in a new class called COX-2 inhibitors because they may cause strokes and heart attacks, and drug makers face multi-million dollar liability suits.
And the U.S. Food and Drug Administration has ordered strict warnings to be put on packages of painkillers known as non-steroidal anti-inflammatory drugs or NSAIDS, including naproxen, a popular NSAID sold over-the-counter by Bayer under the brand name Aleve.
The warning labels were ordered because of some studies that suggested NSAIDS might also raise heart risks.
"Particularly for safety data, 'truth' may come in small doses. We firmly believe that results from trials should be published regardless of the direction, magnitude, or statistical significance of the observed results," said Barbara Martin of the John Hopkins University School of Public Health, who worked on the study.
Writing in the Public Library of Science journal PLoS Clinical Trials, Martin and colleagues said they looked at data from a trial designed to see if Celebrex might help prevent Alzheimer's disease in high-risk patients.
The 2,500 elderly volunteers were given either COX-2 inhibitor Celebrex, naproxen or a placebo for up to 3-1/2 years. It was stopped when concerns rose over the safety of COX-2 inhibitors.
The trial showed no increased or decreased heart risk for Celebrex, known generically as celecoxib, compared to placebo.
But it did show an increased risk for naproxen.
Over three years, 5.5 percent of the patients getting Celebrex had a stroke, heart attack or were diagnosed with congestive heart failure, while 5.6 percent of those getting a placebo did.

In comparison, 8.25 percent of the naproxen patients had such a serious cardiovascular incident or death.
Dr. Steve Nissen of the Cleveland Clinic in Ohio said the trial's findings were "completely unreliable."
"The stopping of the study early was improper and it led to erroneous conclusions," Nissen said in a telephone interview.
"We know from very large epidemiological (population) studies and all sorts of studies that naproxen is a safe drug, perhaps the best of the NSAIDS," added Nissen, an outspoken expert on the safety of NSAIDS and COX-2 inhibitors.
Just last week, a much smaller study led by Dr. Michael Schiff of the Denver Arthritis Clinic suggested that naproxen did not raise the risk of heart attack and stroke.
"We don't have the full answers," Nissen said. He has a safety trial with 21,000 patients under way to compare naproxen with Celebrex and placebo.