Last week, Merck abruptly recalled Vioxx, an arthritis treatment and one of the company’s top-selling drugs, after an internal study showed that patients taking the drug were more likely to suffer a cardiac event than those taking a placebo.
The Journal’s report, citing a study by the Food and Drug Administration, said that from Vioxx’s approval in 1999 through 2003, an estimated 27,785 heart attacks and sudden cardiac deaths would have been avoided if Celebrex, a competing drug made by Pfizer Inc., had been used instead of Vioxx.
The article said the figures were projections based on findings from an analysis of a database of patients of Kaiser Permanente, a large health-maintenance organization.
No comment was immediately available from the FDA or Merck.
Analysts said Merck is now confronting the possibility of multiple lawsuits in connection with the recall.
The FDA study has not been released to the public, but a copy has been requested by Senate Finance Committee Chairman Charles Grassley, R-Iowa, who is investigating how the FDA handles safety concerns, the Journal said.
The study drew on data from about 1.4 million Kaiser patients, who had taken one of the painkillers called nonsteroidal anti-inflammatory drugs, or NSAIDs. That included 40,405 patients who had taken Celebrex and 26,748 who had taken Vioxx, the Journal said.
A Merck spokesman told the Journal that the company could not comment on the full study, “as we have not yet had the opportunity to review it."
relievers may cause problems
At the same time, scientists and European regulators are now questioning the safety of other pain relievers like Vioxx, saying these medications also might raise the risk of heart attack and stroke.
On Wednesday, the European Medicines Agency in London announced it would review drugs similar to Vioxx. And researchers writing in the New England Journal of Medicine voiced their concerns as well with such drugs as Pfizer’s popular Celebrex.
The medical journal published two reports on the issue Wednesday on the Internet, ahead of their planned publication, because of their public health importance.
Studies done five years ago when Celebrex and Vioxx were approved suggest that 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 who led the studies, which were designed by him but funded by the drug companies.
“I believe this is a class effect,” meaning that the problem also applies to Celebrex and Pfizer’s newer, similar drug, Bextra, which remain on the market.
He called on the FDA to change its advice to patients and doctors to reflect the new safety concerns. In a separate report also released by the medical journal, Dr. Eric Topol of the Cleveland Clinic chastises the FDA for not requiring Merck to do studies investigating heart problems with Vioxx when hints of them first appeared years ago.
Pfizer’s medical director, Dr. Gail Cawkwell, insisted that its drugs are safe.
“The data for Celebrex is robust and exceeds, in the length of patients in studies and in the size of studies, the data Vioxx has,” she said.
stomach, risk the heart?
She called FitzGerald’s 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.
FDA officials did not immediately return phone calls seeking comment.
When Merck voluntarily withdrew Vioxx, FDA officials said heart problems were unique to that drug and that the mechanism underlying them 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.
The studies will be published in the Oct. 21 print edition of the medical journal.