Advisers vote to recommend keeping Celebrex, Vioxx and Bextra available while finding all raise cardiovascular risks
By Amanda Gardner
HealthDay Reporter
FRIDAY, Feb. 18 (HealthDay News) -- The popular prescription painkillers Celebrex, Vioxx and Bextra significantly raise cardiovascular risks, but they should stay on the market, a U.S. Food and Drug Administration panel determined Friday.
In three unanimous votes in succession, the advisory group found that all three drugs in the class of painkillers known as cox-2 inhibitors carry increased heart risk.
But despite split votes on the question of keeping the drugs on the market, the panel appeared to determine that their benefits outweighed their risks.
The advisory group, ending three days of hearings, approved recommending continued use of Pfizer's Celebrex by a vote of 31-1. A majority were also in favor of requiring a black-box warning on the label to flag the heightened heart risk.
The panel's vote to recommend continued use of Pfizer's painkiller Bextra passed 17-13, with two abstentions.
And the support for keeping Merck's Vioxx passed 17-15.
The Vioxx vote appeared to ensure the return of the hugely popular drug, which Merck removed from pharmacy shelves last fall after its own clinical trials showed the increased heart risks. On Thursday, Merck announced at the hearings that it would consider resuming sales of Vioxx if the advisers found the benefits outweighed the risks.
The panel's decisions, which have yet to include all the warnings under discussion, will be forwarded to the FDA for final action. The agency had promised, as the hearings got under way Wednesday, that it would act fairly promptly, and while it is not required to follow its advisers' recommendations, it usually does.
The panel's rapid actions followed a summation by committee chairman Dr. Alastair Wood, who made it clear Friday morning at the end of public testimony that there were significant safety issues posed by all the cox-2s.
"It's important to recognize that this is a far larger randomized safety signal than we have seen from any of the drugs that have been withdrawn for safety reasons," Wood told the assembled crowd.
"This is a much bigger safety problem than with the other drugs the FDA has withdrawn," Wood added. "And the only reason we have agonized so much is that this is a relatively common problem, and therefore much harder for us to be sure the signal is clear."
While acknowledging that patient testimony heard on Thursday was "both moving and important," Wood, of Vanderbilt University Medical School, added, "No one has been able to demonstrate specifically a better response amongst any of these drugs in individual patients in any randomized way."
All of this, he added, brings the panel of 32 scientists and doctors to the $64 million question: "What should we do?"
"The committee needs to act in a way that limits the hazard to patients," he said. "The public has a right to expect us to do that. When we leave here tonight, we need to have made really clear recommendations to the FDA, which will help them move forward."
Wood's remarks came right after representatives of drug companies made last-ditch presentations in defense of their products.
And they followed Merck's surprise announcement that it may put Vioxx back on the market, depending on the hearing outcome.
"If the advisory committee and the FDA conclude that the benefits of this class outweigh the risks in some patient populations, then we would have to consider the implications of these new data given the unique benefits Vioxx offers," the Merck & Co statement said, according to a CNN report.
The popularity of painkillers like Vioxx was very much in evidence during testimony from the public at the hearing. At least a dozen people took to the podium with personal stories of pain relief and asked the FDA advisers to keep the cox-2 inhibitors on the market.
Meanwhile, the European Medicines Agency, Europe's most powerful drug regulators, on Thursday mandated stronger warnings on cardiovascular risks for all the cox-2 painkillers, the Associated Press reported.
Early Thursday, FDA whistleblower Dr. David Graham had delivered damning testimony on Vioxx and the other cox-2s, whose original design was to reduce the risk of gastrointestinal danger.
"There's a one-in-50 chance that a male aged 65 to 74 will have a heart attack this year. Increase that fivefold with high doses [of Vioxx]," Graham told the FDA advisers.
"That's what happened with VIGOR [a 2000 manufacturer's trial comparing gastrointestinal effects of Vioxx and another painkiller, naproxen]. If you have millions of people taking high doses, you're going to get numbers that balloon out. Because of the high background rate of the underlying event, there are many more cases," he said.
The fact that randomized controlled trials such as VIGOR tend to include healthy people may have skewed the perception of risk, the FDA scientist added during two hours of testimony.
"People are harmed by rofecoxib [Vioxx]," Graham testified before a standing-room-only crowd.
In their testimony, both Graham and Dr. Richard Platt, of Harvard Medical School, tried to demystify the different types of studies available on nonsteroidal anti-inflammatory drugs (NSAIDs), the group of medications that includes cox-2s.
While Platt was matter-of-fact in his descriptions of how different studies are designed and how that might affect outcomes, Graham was more forthcoming on which specific studies he deemed good or bad.
Graham said he believed the negative cardiovascular effects of Vioxx were dose-dependent, meaning higher doses had a bigger effect, and that the risk kicked in immediately, within the first 30 days. Both issues have been subjects of debate.
Celebrex had no effect on the heart at doses of 200 milligrams or less, Graham added, but did have an increased risk at higher doses. Naproxen, which is a traditional NSAID, has no protective effect, he contended.
And, he added, the little information that exists on Bextra indicates no risk at small doses.
SOURCES: Feb. 18, 2005, U.S. Food and Drug Administration (FDA) advisory panel hearings; Richard Platt, M.D., Harvard Medical School, and David Graham, M.D., medical officer, Center for Drug Evaluation and Research, FDA, Washington, D.C.; CNN; Associated Press; Bloomberg
Copyright © 2005 ScoutNews, LLC. All rights reserved.
