Doctors who led three studies showing prescription painkillers called COX-2 inhibitors raise the risk of heart attacks and stroke said Tuesday the whole class of drugs was in danger of being pulled from the market.
One day before a Food and Drug Administration panel begins discussing the future of such drugs, the New England Journal of Medicine published details of three studies stopped early because patients taking the drugs were having more heart attacks, strokes and other adverse events than patients not taking them.
“I think we are at risk of losing the class of drugs,” said Dr. Robert Bresalier of the University of Texas M.D. Anderson Cancer Center, who was studying one of the drugs, Vioxx, known generically as rofecoxib, in a colon cancer trial.
Merck & Co. Inc. withdrew Vioxx in September after learning the results of Bresalier’s trial, which showed Vioxx almost doubled the risk of heart attacks, strokes and other major adverse events.
Bresalier told reporters his trial also showed Vioxx worked at least as well as aspirin to prevent colon cancer. That data will be published later this year, he said.
He and other experts said those benefits would need to be weighed against the potential risks. “I think the loss of some of these drugs will create a void,” he told reporters in a telephone briefing.
But Dr. Jeffrey Drazen, editor of the New England Journal of Medicine, said that since there were well-established alternatives to those drugs, “it is reasonable to ask whether the use of the drugs can now be justified.”
The drugs are sold mainly for long-term pain relief in arthritis and other conditions,
Tripling mortality
In a second report published by the journal, Dr. Scott Solomon and colleagues at Brigham and Women’s Hospital and Harvard Medical School found Pfizer Inc.’s Celebrex doubled or even tripled deaths from heart attack, stroke or heart failure, depending on the dose.
Their study involved more than 2,000 patients who were also taking the drug to see if it could prevent colon cancer.
In a third report, Dr. Nancy Nussmeier of the Texas Heart Institute at St. Luke’s Episcopal Hospital in Houston and colleagues detailed their study using a third agent, Pfizer’s Bextra, in heart surgery patients.
They found that 7.4 percent of those given the drugs had an adverse event — such as heart attacks, kidney failure, ulcers and complications of wound healing — compared with 4 percent of those given placebo alone.
The studies are among several others showing the drugs raise heart risks.
Ironically, COX-2 inhibitors, which have only been on the market for six years, were designed to be safer than aspirin and related drugs called non-steroidal anti-inflammatory drugs or NSAIDS.
NSAIDS affect two compounds made in the body called prostaglandins — COX-1 and COX-2. Those drugs can also cause severe gastrointestinal bleeding in some people and kill an estimated 16,000 Americans a year.
The COX-2 inhibitors were meant to affect the inflammatory prostaglandin, cyclooxygenase-2, while leaving alone COX-1 and thus, drug makers hoped, sparing the stomach.
But they do not work any better than NSAIDS to relieve arthritis pain in most people.
Bresalier said for many people, acetaminophen, best known under its brand name Tylenol, was a good and safe choice.
“There is no pharmacologic agent out there that doesn’t have great benefits or risks,” he said.
