Pfizer warned doctors yesterday that one of its best-selling painkillers, Bextra, might increase the risk of heart attack or stroke in coronary artery bypass surgery patients.
The announcement comes just two weeks after Merck removed from the market its painkiller, Vioxx, which is in the same class of medicines as Bextra, because a study showed that the risk of heart attacks doubled for patients who had taken Vioxx 18 months or longer.
Pfizer said a clinical study involving more than 1,500 patients showed that those who had undergone bypass surgery and had taken Bextra intravenously and orally were at higher risk for heart attacks. An initial study last year raised similar concerns in the same kinds of patients.
The painkillers known as COX-2 inhibitors, which include Bextra and Vioxx, have been widely prescribed to people with arthritis. Mercks decision to withdraw Vioxx cast suspicion on the safety of drugs in that class. Now Pfizers warning is sure to fuel the debate about the overall safety of these drugs for all patients.
Officials of the Food and Drug Administration said yesterday that the agency would convene a panel of independent experts in January to discuss these issues. Regulators abroad have also indicated plans to review COX-2 drugs.
Pfizer said it was already conducting research into whether Bextra increases the risk of heart attacks in people taking the drug for chronic pain. The company also issued a warning yesterday about an extremely rare and potentially fatal skin reaction to Bextra.
In addition to Bextra, Pfizer also makes Celebrex, the best-selling COX-2 drug on the market. Bextra is the companys new and faster-acting version of Celebrex.
Pfizer says there is no evidence that its drugs have problems similar to Vioxx because they are chemically different. Although Bextra is not approved for use for surgery patients, Pfizer said its studies had shown that general surgery patients as opposed to bypass patients are not at higher risk for heart attacks.
But some doctors say this group of drugs may work in a way that increases the risk of heart problems for some patients, and they point to this latest information as additional reason for concern.
There are serious questions to be addressed here, said Dr. Garret A. FitzGerald, a University of Pennsylvania cardiologist and pharmacologist who raised concerns about the painkillers in The New England Journal of Medicine this month.
But Dr. FitzGerald also emphasized that these drugs are useful for certain patients. We absolutely shouldnt yank these drugs as a class, he said.
Other doctors also expressed concerns about the new information from Pfizer. Its going to require a lot of really serious looks, said Dr. David Campen, a rheumatologist for Kaiser Permanente in California, a major health network, who has also been involved in research on some of these drugs.
Millions of people have taken these drugs for pain and chronic conditions like rheumatoid arthritis, and sales of these three drugs Vioxx, Celebrex and Bextra exceeded $6 billion last year.
Regulators in Europe are expected to make a decision as soon as next week about whether to take any action on the drugs. The F.D.A.s expert panel will review whether Celebrex and Bextra are safe, Dr. Sandra Kweder, acting director of the administrations office of new drugs, said in an interview yesterday.
While no study of either drug analyzed by the agency so far has been cause for concern, Dr. Kweder said, the agency is not sure it has all the information it needs. The agency is aware of the two studies involving the intravenous form of Bextra, but its unclear what the relationship is with the oral form, she said.
Other recent studies suggesting that all COX-2 inhibitors may have safety problems are still being analyzed by the agency, she said. Uncertainty over the safety of drugs is not uncommon, Dr. Kweder said, and that is something we have to take into account with regard to every decision we make about marketing a new drug and every decision we make about withdrawal of a drug.
But some doctors say because the benefits of COX-2 drugs are so unclear, the advantages of taking one of these painkillers may not outweigh these risks.
You have to treat people who are high risk conservatively, Dr. Campen said.
The F.D.A. will take this into account, Dr. Kweder said. She also noted that neither Celebrex nor Bextra had been proved to be any better than older medicines like ibuprofen at guarding against stomach bleeding, a benefit often cited with these drugs, and neither had been proved to be any better at relieving pain than older drugs.
The agency will have to balance the risks and benefits of these drugs. Thats what were going to ask the advisory committee to do, she said.
Since the Vioxx withdrawal, Pfizer has been emphatic in distancing its drugs from Vioxx and playing down concerns about higher risk for heart attack and stroke. The company says it is even conducting research into whether Celebrex might reduce the risk of such events.
Many doctors have said it is critical that research be conducted to settle this issue. Its a trial long overdue, said Dr. Eric J. Topol, chairman of cardiovascular medicine at the department at the Cleveland Clinic, who said the information about what happened in bypass patients was very worrisome.
Dr. FitzGerald criticized Pfizer for not making this latest information public more quickly since the company had completed the study in the spring. Pfizer said it could not have released this information earlier because it had to analyze the information.
I thought we took a rather extraordinary step, said Dr. Mitch Gandelman, a Pfizer executive, who said the company released the information before it normally would to quickly share it with doctors.Pfizer officials emphasized that the news about Bextra does not implicate Celebrex.