Vioxx-Like Risks Linked to Another Pain Pill
The widely used pain reliever diclofenac poses the same cardiovascular risk as the withdrawn drug Vioxx and should not be used by people with heart disease or high blood pressure, researchers reported Tuesday.
Diclofenac, an older drug sold as Cataflam or Voltaren, increased patients’ chance of heart attack by 40%, according to an analysis of 23 clinical studies -- the same risk observed in patients who took low doses of Vioxx.
The report was released early by the Journal of the American Medical Assn. because of its health implications.
Diclofenac, which has been sold for more than 30 years, is available only by prescription in the U.S. and is not widely used here. But it is sold over the counter elsewhere and ranks among the most popular pain relievers in the world.
But now, “there is no reason to keep it on the market,” said Dr. Curt D. Furberg of Wake Forest University, who was not involved in the study. “It clearly increases the risk of heart attack, and patients have other choices.”
Dr. David Henry of the University of Newcastle in Australia, an author of the study, said that diclofenac posed little risk for younger people with no signs of heart disease, but that given the availability of other drugs, “I would say it has no saving graces.”
The FDA said in a statement that it did not consider the findings on diclofenac conclusive, but that the study warranted further review.
The report contained reassuring findings about some other pain relievers. Naproxen, sold over the counter as Aleve and by prescription as Naprosyn, posed no cardiac risk.
Celebrex was safe at recommended doses of 200 milligrams or less a day. Henry said he could not give Celebrex “a clean bill of health” because other studies have detected increased cardiovascular risks at doses of 400 milligrams or greater a day.
“Naproxen looks best from a cardiovascular point of view,” he said. “It is an old, cheap generic drug, and we would tend to favor it.”
Because naproxen can cause ulcers and bleeding, patients should take the drug with medicines used to treat ulcers and control stomach acid, such as Prilosec, Henry said.
With his colleague, Dr. Patricia McGettigan, Henry analyzed the results of clinical studies of eight pain relievers involving more than 1.2 million patients. All drugs in the analysis belonged to a class of medications known as nonsteroidal anti-inflammatory drugs, or NSAIDs. About 30 million people worldwide take an NSAID daily for pain and inflammation.
Two drugs included in the analysis, Vioxx and Celebrex, belong to a subset of NSAIDs known as Cox-2 inhibitors, which were developed as stomach-friendly alternatives to older NSAIDs, such as ibuprofen and naproxen.
The Cox-2 drugs were tremendous moneymakers because they were expensive and widely used. But in September 2004, Merck & Co. removed Vioxx from the market after it was found to cause heart attacks in some patients.
The latest study confirmed the cardiovascular risks of Vioxx, concluding it was not safe at any dose. The chance of heart attack was 33% higher at the daily 25-milligram dose -- in the range of risk associated with diclofenac -- and more than double at doses above 25 milligrams.
Researchers found a hint of elevated cardiovascular risk with ibuprofen, sold as Advil or Motrin, and piroxicam, sold as Feldene, but the increases were not significant on a statistical basis.
Added risk was associated with meloxicam, sold as Mobic, and indomethacin, sold as Indocin, but the findings were based on a limited number of reports.
Tuesday’s study seemed to bring some clarity to the confusion that has surrounded pain relievers since the withdrawal of Vioxx two years ago. Assailed for failing to recognize the dangers of Vioxx sooner, the FDA in April 2005 said all prescription NSAIDs should carry a “black box” warning -- the strongest possible -- about cardiovascular risk.
The latest study showed the FDA’s relabeling order was too broad and based on inadequate evidence, Furberg said. “The FDA has to reassess the scare it created,” he said. “It said every painkiller is harmful, and that clearly is not the case.”
The FDA, however, said the warnings remained appropriate because cardiovascular risk appeared to be common to all NSAIDs and it did not have enough clinical information to distinguish any differences in risk among the drugs.
“This is a tough call for the FDA,” said Dr. Steven Nissen of the Cleveland Clinic, who as a member of an FDA advisory committee endorsed the strong warnings. Although informative, the study’s analysis does not have the weight of a head-to-head clinical trial, he said.
Indirectly, the diclofenac findings could be bad news for Merck. The company has reported that its new drug Arcoxia, a potential successor to Vioxx, has the same cardiovascular risks as diclofenac.
Dr. David Graham, of the FDA’s office of surveillance and drug safety, said Arcoxia, which is now being sold in 62 countries, should not be approved in the U.S. because it was unsafe.
Graham wrote in an editorial accompanying the study that the FDA’s decision on Arcoxia would be a test of the FDA’s commitment to patient safety.
The FDA said it could not comment on a drug that was under review.
Merck said its results were consistent with FDA’s finding of no differences in the risks posed by NSAID drugs.
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