The focus now shifts to COX-2 inhibitor class
Some providers demanding investigations now
Now that Merck & Co. has withdrawn rofecoxib (Vioxx) from the market because of increased risk of heart attack and stroke, the attention is shifting to the other drugs of this class.
Rofecoxib, celecoxib (Celebrex), and valdecoxib (Bextra) are a subclass of nonsteroidal anti-inflammatory drugs (NSAIDs) that selectively block the enzyme COX-2 (cyclooxygenase-2). When Merck announced the rofecoxib withdrawal, it said that its study results were not necessarily applicable to others in the COX-2 inhibitor class.
A rheumatologist who says rofecoxib has benefited many of his patients is not too concerned about the cardiovascular risk of the other two drugs — at this point. "I think we should go by the data that we have," says Hayes Wilson, MD, a rheumatologist at Piedmont Hospital in Atlanta and a medical adviser for the Arthritis Foundation. "Vioxx was pulled because they got new prospective data that said that it was trending in the wrong direction for heart disease. But the data for Celebrex and Bextra are that it is safe. Any medication that is strong enough to help you is strong enough to potentially give you a side effect. Any time you take a medication, it is a calculated risk."
The other COX-2 inhibitors, though, are a concern for Gordon J. Vanscoy, PharmD, CACP, MBA, assistant dean for managed care and associate professor of pharmaceutical sciences at the University of Pittsburgh School of Pharmacy. He also is chairman and chief executive officer of University Pharmacotherapy Associates in Monroeville, PA. "I definitely think there needs to be more studies."
It is not known if the problem is a class effect, he says. Are the side effects inevitable after the broad use of the COX-2 products, or are they truly specific to the chemical structure of rofecoxib?
Vanscoy foresees more clinical monitoring of patients on celecoxib and valdecoxib to see if the patients experience any of the same serious cardiovascular side effects as those taking rofecoxib. "I think there is an obligation on behalf of the other manufacturers to ensure that we don’t have an analogous situation."
The call to arms
Other physicians are alarmed about the rofecoxib withdrawal. The New England Journal of Medicine published two editorials from such physicians; the editorials were published on its web site on Oct. 6 and will appear in the Oct. 21 printed issue.
One of the editorials calls for further investigations of the COX-2 class. The APPROVe (Adenomatous Polyp Prevention on VIOXX) trial, the results of which led Merck to pull rofecoxib from the market, has shifted the burden of proof, says Garret A. FitzGerald, MD, professor and chair of the department of pharmacology at the University of Pennsylvania School of Medicine in Philadelphia. "[It] now rests with those who claim that this is a problem for rofecoxib alone and does not extend to other coxibs.
"We now have clear evidence of an increase in cardiovascular risk that revealed itself in a manner consistent with a mechanistic explanation that extends to all the coxibs. It seems to be time for the FDA urgently to adjust its guidance to patients and doctors to reflect this new reality."
It is essential to determine whether the cardiovascular risk is or is not a class effect, FitzGerald says. "We must remember that the absence of evidence is not the evidence of absence."
The withdrawal is a warning to the class, although [the risks] may not hold across the class, Vanscoy says. "You are better off being safe than sorry."