MONDAY, Dec. 20, 2004 (HealthDayNews) -- The U.S. government announced Monday that it is halting the use of the popular painkiller Aleve in a clinical trial because patients taking it showed a higher risk for developing heart trouble.
It was the second time in as many workdays that the National Institutes of Health (NIH) suspended the use of an arthritis drug in a trial. On Friday, the agency said it was stopping the use of Celebrex in a trial involving cancer patients.
Monday's announcement centered around a trial testing whether Aleve or Celebrex could prevent Alzheimer's disease. And while several recent studies have cast the family of drugs Celebrex belongs to in an unhealthy light, this is the first in which a trial using an over-the-counter arthritis drug was found to cause trouble.
Aleve and Celebrex are different types of nonsteroidal inflammatory inhibitors (NSAIDs). Celebrex and two other drugs that have been tied to heart trouble this year, Vioxx and Bextra, belong to a subset of stomach-friendly NSAIDs called cox-2 inhibitors.
Although participants in the Alzheimer's trial will no longer be taking either Aleve or Celebrex (celecoxib), they will continue to be monitored.
"We are suspending the use of the drugs within this trial," Dr. Elias Zerhouni, director of the National Institutes of Health, said at a news conference Monday evening. "The trial itself is not suspended and will continue."
Aleve (naproxen) belongs to an older family of drugs known as cox-1 inhibitors.
The cox-2 class of drugs has fallen under a dark cloud in recent months. In September, Vioxx was pulled from the market due to an increased incidence of cardiovascular problems. Then on Friday, a trial involving another cox-2, Celebrex, was halted due to similar concerns among colorectal cancer patients. A third cox-2 inhibitor, Bextra, has also shown evidence of problems.
In the wake of the cox-2 revelations, many people had turned to the older cox-1 inhibitors for pain management. Naproxen has been on the market as a prescription drug since 1976 and as a lower-dose, over-the-counter drug (Aleve) since 1994.
The current trial, sponsored by the National Institute on Aging, was trying to determine if NSAIDs might have a preventive effect on Alzheimer's. About 2,500 participants were divided into three groups and randomly assigned to receive either 220 milligrams of naproxen twice a day, 200 milligrams of Celebrex twice a day, or a placebo, for up to three years.
Investigators had noticed a "weak signal" towards cardiovascular events in the naproxen arm, but decided to suspend the use of both drugs after the news about Celebrex broke last week.
"The events of last week and the news about celecoxib put things into a different light for us, because in part we found it very difficult to ask our participants to continue to stay on treatments when they knew that they had a chance of receiving Celebrex, about which there has been a lot of adverse publicity of late," said study leader Dr. John Breitner, who is with the Veterans Affairs Medical Center and the University of Washington in Seattle.
Breitner said the research team had noticed a 50 percent increased risk of cardiovascular events in naproxen patients, but cautioned that these were "small numbers." In all, 70 patients in the trial experienced heart attacks or strokes, out of a total of 2,500 people. There were about 23 deaths, about equally distributed across the three groups. In all, the risks did not approach those seen last week with Celebrex, Breitner added.
All of the participants were called over the weekend and told not to take any more medication.
Officials from the U.S. Food and Drug Administration said the agency would assess what regulatory actions would be appropriate. "Suspending a research trial where a benefit is only potential in nature is very different from making a decision about whether a drug should stay on the market," Zerhouni stated.
"FDA advises patients who are currently taking over-the-counter naproxen to carefully follow the instructions on the label," said Dr. Steven Galson, head of the FDA's Center for Drug Evaluation and Research. "Patients should not exceed the recommended doses for naproxen, and no longer than 10 days."
Naproxen is also contained in prescription products, Galson added. Individuals taking these products should consult with their doctors.
More information
The Alzheimer's Association has more on Alzheimer's disease.
