Naproxen, a common painkiller sold under the brand name Aleve, appears to increase the risk of heart attacks and strokes, the government said yesterday, making it the third major painkilling drug linked to heart problems in recent months.
Officials suspended naproxen’s use in a national study to prevent Alzheimer’s disease, after finding that those taking the drug had a 50 percent higher risk of heart problems than those taking a placebo, or dummy pill, according to a preliminary analysis.
Doctors at the US Food and Drug Administration last night recommended that all patients taking naproxen without a prescription limit usage to no more than 10 days and 440 milligrams a day unless they consult their doctor.
They said the potential problems with naproxen raise questions about ibuprofen and other common over-the-counter painkillers in the same class, known as non-steroidal anti-inflamatory drugs. Previously, the heart problems cited by the government appeared limited to the prescription painkillers Vioxx, Celebrex, and Bextra, all members of a class known as cox-2 inhibitors.
The FDA said the Alzheimer’s study, funded by the National Institutes of Health, was the first evidence suggesting cardiovascular risk with a painkiller that’s been on the market since 1976. The FDA said it was not contemplating any specific regulatory action in the next few days, such as banning direct-to-consumer advertising, as it did for Pfizer Inc.’s Celebrex.
“We agree that this is confusing,” said Sandra Kweder, the FDA’s deputy director of the Office of New Drugs.
Dr. Elias A. Zerhouni, director of the NIH, said his agency’s decision to stop giving painkillers to patients in the study was guided more from the “do no harm” philosophy of medicine than statistical significance of risk faced by the patients.
“It is the prudent thing to do to not take the risk, given the benefit is very hypothetical,” Zerhouni said. He said patients who use naproxen for pain control should consult with their physician.
Dr. Elizabeth Tindall, an Oregon doctor whose arthritis patients take up to 1,500 mg of naproxen daily, was stunned by the news.
“I think it’s just more scary information that will be problematic,” said Tindall, president of the American College of Rheumatology. “That will scare them and they won’t want to take anything. Or they’ll get so cynical, they just won’t listen to anything, anymore.”
The multiyear Alzheimer’s study was looking at whether Celebrex or naproxen could prevent development of the mentally crippling disease in healthy older adults. About 2,400 participants, including 434 from New England, were taking one of those drugs or a placebo, according to Dr. Robert C. Green, a Boston University neurologist involved in the study.
On Friday, after the government reported finding heart problems linked with Celebrex in another study, NIH officials decided that patients in the Alzheimer’s trial would consider Celebrex too risky. Officials halted a long-term cancer prevention trial Friday after studies indicated that 800 mg of Celebrex taken daily for long periods tripled heart risks.
Boston University’s Green said patients were called over the weekend and told to stop taking the drugs because of the news Friday about heart risks associated with Celebrex. Local doctors and nurses involved with the study were not aware of the issues with naproxen until yesterday afternoon, he said.
Doctors monitoring the safety of the Alzheimer’s study took a closer look at the heart complications over the weekend and found a problem not with Celebrex, but with naproxen, said Dr. John Breitner of the Veteran’s Affairs Medical Center in Seattle, the trial’s principal investigator.
Green said some study participants “seemed relieved” that the study was being stopped. “Others were disappointed, because this research is to answer the question as to whether these compounds could prevent the development of Alzheimer’s disease,” he said. “These are people very committed to the research.”
One patient in the study, Dr. Byron Roseman of Chelmsford, said he was more concerned about the disruption to the study than about any risk to his heart. Roseman, 76 and a semi-retired pediatrician, said he had watched his mother succumb to Alzheimer’s and felt the study provided hope of preventing the “horrible disease.”
“Anything we can do, even if there is some risk, should be done,” to prevent Alzheimer’s, he said.
Nationally, officials said 70 patients in the study had suffered heart attacks and strokes, but they would not say how many had taken naproxen. Green said some New England patients in the study had suffered cardiovascular problems, but “no more than we would expect for this age group.”
Meanwhile, at least two Congressional committees are reviewing the FDA’s oversight of drug safety and critics have called for Bextra and Celebrex to yanked from the market. Pfizer stock has dropped 16 percent since Thursday. News of the government’s concerns about naproxen was not revealed until the stock markets closed yesterday. Neither Pfizer, which makes Celebrex, nor Bayer AG, which makes Aleve, could be reached for comment last night. Naproxen, now a generic drug, is also sold under many store brands.
In light of Friday’s finding in the cancer prevention trial, the NIH said it would review four dozen studies that it funds using the painkiller Celebrex. The agency said the fate of the other studies is unclear.
All told, 70 people had heart attacks or strokes in the study and 23 people died with no statistical difference in death rates among the people taking painkiller vs. placebo, Breitner said.
While the rate of heart problems was not as high for naproxen as the halted Celebrex study, “they’re enough to cause some concerns,” he said.