Use of the painkiller Vioxx (search) poses the risk of hundreds to thousands of additional heart attacks in older men, a Food and Drug Administration whistleblower told a panel reviewing the safety of painkillers on Thursday.
Dr. David Graham (search) said studies indicate a range of increased heart attack risk which translates to as few as 400 or as many as 10,800 additional heart attacks in men aged 65 to 74 at low doses of the drug.
Vioxx was pulled off the market Sept. 30 by its maker, Merck & Co. (search), after a long-term study indicated an increased risk of heart problems and stroke. Graham spoke at a three-day meeting of FDA advisers assessing the safety of Vioxx and its related painkillers Celebrex and Bextra.
While some studies of Vioxx showed a statistical increase in risk, Graham commented that "patients enrolled in clinical trials are generally healthier than patients in the real world, so models underestimate the actual population impact."
The typical user of this type of painkiller is someone in their 60s, not only men, with other health problems, Graham said. That person already had a one-in-50 risk of heart attack, he said.
He said he believes there is also a risk in taking Celebrex (search) at high doses, but does not have enough information on Bextra.
Graham previously had complained that he was being muzzled by his agency because officials did not want him to discuss a pair of studies of the hazards of drugs that had not yet been published in peer-reviewed journals.
He included the data in his talk, however, thanking FDA Acting Director Lester Crawford for making it possible for him to do so.
Asked if there was anything he was leaving out, Graham responded: "I've been able to present what I thought it was important to present."
"I'm attracted to the Cox-2 hypothesis," Graham said, referring to suggestions that the heart problems cover the class of drugs called Cox-2 inhibitors (search), which includes the three under review.
An official of Merck said at Wednesday's hearing that the problem appears to affect the whole class of drugs, while Pfizer Inc., the maker of maker of Celebrex and Bextra argued those products are safe.
When Merck withdrew Vioxx on Sept. 30 the company acted because it feared some problem with the drug itself was leading to the strokes and heart trouble.
But Dr. Ned S. Braunstein, senior director of Merck Research Laboratories, told the panels that since then studies suggesting similar problems with Celebrex and Bextra have changed his mind.
"The data strongly suggest it is a class effect" for all drugs of that type, Braunstein said.
The drugs, designed to help people in chronic pain from conditions such as arthritis, are known as Cox-2 inhibitors. At least two other Cox-2 drugs are awaiting approval from the FDA, Arcoxia from Merck and Lumiracoxib from Novartis Pharmaceuticals.
The Cox-2 drugs have become blockbuster sellers over the past 15 years, offering relief from chronic pain without causing the stomach and intestinal troubles that plague many other pain killers.
The advisory committees are holding a three-day session to gather data on the safety of Cox-2 inhibitors and to make recommendations regarding their future use.
Recommendations could range from limiting these drugs to people not known to be at risk of heart problems, reducing the dose or duration of use, requiring tougher warning labels and even taking the drugs off the market.
An FDA health official told the panels there were preliminary indications of heart problems with Vioxx before it was withdrawn, but it was difficult to sort through conflicting data.
Dr. Lourdes Villalba, medical officer responsible for Vioxx at the FDA's Center for Drug Evaluation and Research, said a study done in 2000 comparing Vioxx with the painkiller naproxen showed a higher rate of heart problems with Vioxx, but other studies had conflicting results.
Dr. Kenneth M. Verberg, Pfizer vice president for inflammation and immunology, defended Celebrex as safe, though he said there is little data on use of the drug for more than one year. Further long-term testing of Celebrex is needed, he said.
Merck's Braunstein said the biggest increase in heart problems occurred after 18 months of use.