Scientists in the United States and Great Britain are calling for a fresh look at Celebrex (search) and other medications similar to Vioxx (search), the heavily advertised arthritis drug pulled from the market last week after a study suggested it doubled the risk of heart attacks and strokes.
In the United States, a cardiologist who had researched these drugs published an article in the New England Journal of Medicine suggesting problems might extend to the entire class of medications, not just Vioxx. Another prominent doctor writing in the same journal charged that the Food and Drug Administration (search) did not do everything needed to make sure the drug was safe. He also called for a congressional review of the matter.
An FDA spokeswoman said the agency had no comment. Last week, FDA officials said problems were limited to Vioxx.
"The proof is really in the real-world data, and it hasn't been borne out," Pfizer's medical director, Dr. Gail Cawkwell, said of the heart problem risk.
The medical journal published two reports on the issue Wednesday on the Internet — more than two weeks ahead of their planned print publication — to help inform doctors and patients considering whether to stop using the drugs.
Studies done five years ago when Celebrex and Merck & Co.'s Vioxx were approved suggest the same mechanism that inhibits inflammation and makes the drugs easier on the stomach than traditional painkillers also blocks a substance that prevents heart problems, according to Dr. Garret FitzGerald, a University of Pennsylvania cardiologist. FitzGerald led the studies, which were designed by him but funded by the drug companies.
"I've been concerned all along," he said. "I believe this is a class effect," not just a problem with Vioxx, he said.
Cawkwell of Pfizer called his contention "an interesting theory," but said, "there is no evidence" of increased risk of heart problems among the 75 million Americans who have taken Celebrex. Long-term studies are not yet available on Bextra, which was approved in 2001.
Celebrex is the 10th most popular drug in the United States, with annual sales of $2.7 billion, up 5 percent in a year, according to IMS Health, a company that tracks drug industry trends.
An article in the medical journal by Dr. Eric Topol of the Cleveland Clinic chastised the FDA for not requiring Merck to do studies investigating heart problems with Vioxx when hints of them first appeared years ago, and for allowing the company to blitz consumers with TV ads touting the drug.
Vioxx was the largest prescription drug withdrawal in history, "but had the many warning signs along the way been heeded, such a debacle could have been prevented," Topol wrote. "Neither Merck nor the FDA fulfilled its responsibilities to the public...I believe there should be a full Congressional review of this case."
Merck and FDA officials said the mechanism underlying the problem with Vioxx wasn't known.
But FitzGerald and colleagues published two studies in 1999 and another in 2001 suggesting that by selectively blocking one of the two substances called prostaglandins that lead to inflammation, these so-called cox-2 inhibitors were sparing the stomach at the expense of the heart.
"There's a good prostaglandin and a bad prostaglandin as far as the heart is concerned," he explained.
Suppressing both, as older painkillers like aspirin and other non-steroidal anti-inflammatory drugs, or NSAIDS do, helps the heart. But shutting down just the "good" one raises the risk of high blood pressure, hardening of the arteries and clotting, he reports.
FitzGerald also challenged Pfizer's contention that no science shows increased risk from Celebrex. The original report from one study involving Celebrex found no increased risk of heart problems, but it covered only six months of a year-long study, according to the cardiologist. A look at the full data "reveals signs of increased cardiovascular risk," he writes.
The medical journal will publish the new reports in its Oct. 21 print edition.
Republican Congressman Tom Davis of Virginia, who chairs the House Government Reform Committee, has sent a letter to FDA's acting commissioner, Dr. Lester Crawford, giving him two weeks to answer questions about how FDA tracks problems with drug safety, how it dealt with issues surrounding Vioxx, and whether the agency will study potential risks in similar drugs.
"In light of Merck's withdrawal of Vioxx from the market and other recent news stories examining FDA's review of the safety and efficacy of antidepressant drug use by children, I am concerned whether FDA has been sufficiently aggressive in monitoring drug safety," Davis wrote.