Naproxen Warning Unjustified, Say FDA Experts

A report last year that linked the pain killer naproxen (search) to heart attacks unnecessarily scared the public, experts charged Friday.

FDA advisory panel members reviewing the safety of the arthritis drug Vioxx and similar drugs accused National Institutes of Health officials of acting irresponsibly when they stopped a study testing the drugs Celebrex and naproxen in preventing Alzheimer’s disease (search). Naproxen is sold under many brand names, including Aleve (search) and Naprosyn (search).

The NIH halted the trial, called ADAPT (search), after data suggested that naproxen raised the risk of heart attack and stroke in study patients.

An earlier study showed that Celebrex had similar risks.

NIH Director Elias A. Zerhouni, MD, released a statement saying that the trial was being stopped “as a precautionary measure to ensure the safety of the study’s participants” and that the researchers made their decision based on the risk/benefit analysis specific to this trial.

Naproxen's Risks Questioned

But one ADAPT researcher told the panel Friday that naproxen’s effect on heart risk was “barely significant” and that the study was not stopped because of safety concerns. Instead, officials halted the trial because of a concern that questions on the safety of Vioxx (search) and related drugs would make study participants reluctant to take their medications and damage the integrity of the study.

“There seemed little practical choice but to do so,” said Constantine Lyketsos, MD, a Johns Hopkins University researcher who was part of the ADAPT study team. Some study patients had already begun to resist taking their drugs, and study directors became fearful that patients would “vote with their feet” and stop participating altogether.

“We feared further erosion” of the study, he said.

Lyketsos also said that study leaders faced an ethical dilemma of continuing with an Alzheimer’s prevention study with no expected immediate benefit to patients, given possible safety concerns with Celebrex, Vioxx, and similar drugs, called Cox-2 inhibitors.

FDA experts harshly criticized the NIH’s announcement, saying that it potentially scared millions of naproxen patients despite some pervious data suggesting that the drug may actually be safer for the heart than Cox-2 drugs.

Studies have suggested that naproxen may carry a lower heart risk than Cox-2 drugs, but researchers remain unsure of its heart safety since it has never been tested against a placebo.

The announcement “had the effect that was the equivalent of screaming ‘fire’ in a crowded auditorium,” said Steven Nissen, MD, a panel member and medical director of The Cleveland Clinic.

Nissen said he and other cardiologists were forced to field calls from hundreds of frightened patients who had read media reports of naproxen’s dangers.

“It caused a panic that was unnecessary, and it shouldn’t have happened, and I hope it doesn’t happen again,” said Nissen. “We can’t do business this way.”

Drugmaker Defends Product

Another expert cautioned that studies presented previously during the committee’s deliberations suggested that other anti-inflammatory drugsclosely related to naproxen may carry heart attack and stroke risk.

“I think we need to accept the fact that all of them have some risk with regard to [heart attack and stroke] risk,” said John T. Farrar, MD, a senior scholar at the University of Pennsylvania Center for Epidemiology and Biostatistics.

Bayer Inc., which makes Aleve, released a statement noting that data it submitted to the FDA committee showed no evidence of increased heart attack or stroke risk with the drug when it is taken as directed.

“Bayer believes the evidence presented to the committee and the subsequent discussions support our confidence that Aleve is safe and effective for the relief of minor aches and pain,” said Erica Peitler, the company’s senior vice president of research and development.

Lyketsos told the committee that ADAPT study leaders will release the study’s results on the safety of naproxen and Celebrex in a medical journal within the next few weeks.

By Todd Zwillich, reviewed by Michael W. Smith, MD

SOURCES: Elias A. Zerhouni, MD, director, National Institutes of Health. Constantine Lyketsos, MD, Johns Hopkins University, ADAPT researcher. Steven Nissen, MD, medical director, The Cleveland Clinic; member FDA panel. Erica Peitler, senior vice president of research and development, Bayer HealthCare Consumer Care. John T. Farrar, MD, senior scholar at the University of Pennsylvania Center for Epidemiology and Biostatistics; member, FDA panel.