HALIFAX - Some Canadian doctors are wondering whether arthritis drugs in the same class as Vioxx, which caused nearly 28,000 heart attacks or deaths in the U.S. before it was pulled off the market in September, might carry some of the same risks.
- FROM SEPT. 30, 2004: Heart attack risk prompts recall of arthritis drug
The 28,000 figure emerged this week as the U.S. Food and Drug Administration released a new report about Vioxx.
In pulling it off worldwide markets more than a month ago, manufacturer Merck & Co. said its clinical trial had found the drug doubled the risk of heart attacks and strokes in patients who took it for more than 18 months, compared to those who took dummy pills.
Now questions are being asked about other drugs in the class known as COX-2 selective inhibitors � including Celebrex, Bextra and Mobicox.
Health Canada newsletter questions Celebrex
The problems with Vioxx were first documented shortly after Health Canada approved it in 1999. As early as the year 2000, Health Canada's adverse reaction newsletter raised the possibility the other top-selling COX-2 inhibitor, Celebrex, could also be harming people.
Then, during a Health Canada teleconference in January of 2002, an expert advisory committee concluded that doctors and patients should be warned of potential negative cardiovascular effects in all COX-2 drugs.
"The safety profile for Celebrex is well-established and is supported by extensive clinical studies in Canada and around the world," the drug's manufacturer, Pfizer Inc., said in a statement Thursday, reacting to news stories about its product.
"Millions of patients have been prescribed Celebrex since its first approval in 1998 and large-scale clinical studies of up to four years showed no increased cardiovascular safety risk."
But Dr. Jim Wright, a researcher with the British Columbia-based Therapeutics Initiative, an independent group that studies the safety and efficacy of drugs, has been warning about the risks of COX-2 inhibitors for years.
"I think there definitely is a very good chance there is a class effect," said Wright.
Database shows serious adverse reactions
Health Canada's adverse drug reaction database now shows virtually the same number of suspected serious adverse reactions have been reported for Celebrex as for Vioxx � more than 450 for each drug.
The database of unproven reports is used by Health Canada as an early warning system.
However, Pfizer's release pointed out that the database contains no information about the patients' underlying conditions, unlike carefully controlled clinical trials.
"Voluntary spontaneous event reporting to health authorities is not designed and cannot be used to determine cause and effect," the release said. "It is essential to remember that the information provided is uncontrolled and may be second-hand or incomplete."
Wright said a definitive answer about the impact of the drugs will lie in good research.
"The only way we'll know is if we do randomized trials," he said. "I've been pushing for trials of these drugs since they came on the market, and if they had done it, we'd have the answer."
Some researchers doubt class effect
Dr. Muhammed Mamdani, the head of drug research at the Institute for Clinical Evaluative Studies in Toronto, doesn't think there's a class-wide effect, although he has some concerns about the drug Bextra.
Still, Mamdani said Health Canada should settle the question by ordering drug companies to do long-term randomized controlled trials.
"The best types of studies should be commissioned by Health Canada to investigate this issue further," he said.
Health Canada says it's now reviewing COX-2s. For example, it has given Pfizer until later this month to come up with safety data on Celebrex.