MONDAY, Jan. 31, 2005 (HealthDayNews) -- A major Canadian study solidifies evidence that the now-withdrawn arthritis drug Vioxx increases the risk of heart attack, and shows that higher doses are associated with a greater risk.
No similar increase in risk was found for Celebrex, another member of the cox-2 inhibitor family of drugs to which Vioxx belongs, said the report by researchers at McGill University in Montreal.
"This is consistent with what most of the other studies have found," said study author Dr. James A. Brophy, an associate professor of medicine at McGill. "But it included many more cases than other studies, so we were able to have more precision. And other studies have not demonstrated dose-dependency."
The findings appear in the Feb. 1 online edition of the Annals of Internal Medicine.
The study included 113,927 older residents of Quebec who took painkillers between January 1999 and June 2002. The incidence of heart attacks increased 21 percent among those who took low doses of Vioxx and by 73 percent in those who took high doses -- more than 25 milligrams a day, the study found.
Taking aspirin decreased the risk for people who took lower doses of Vioxx but not for those who took the higher doses, according to the study.
"The importance of the new study is that it separates Vioxx from other cox-2 inhibitors," said Dr. Todd Schlifstein, an assistant professor of rehabilitation medicine at New York University School of Medicine. He called it "an impressive study because of its vast size and the number of years over which it was done."
The fact that aspirin did not moderate the increased risk of high-dose Vioxx is "a pretty impressive sign that there is an increase in risk," he said.
Vioxx and other cox-2 inhibitors became popular because they decrease the incidence of gastrointestinal bleeding and stomach ulcers in people regularly taking painkillers such as aspirin and other nonsteroidal anti-inflammatory drugs. They were marketed aggressively, so that annual sales of Vioxx mounted to $2.5 billion before Merck & Co., the manufacturer, withdrew the drug from the market last September when reports of increased heart attack risk emerged.
The drug was being greatly overprescribed, said a study reported last week in the Archives of Internal Medicine by Dr. C. Caleb Alexander, an instructor in medicine, and his colleagues at the University of Chicago.
The study found that 12 percent of patients at low risk of gastrointestinal problems were prescribed cox-2 drugs in 1999, and that the number rose to 40 percent in 2001 before declining slightly in 2002.
"The bottom line of our study was that we found a considerable proportion of cox-2 users had little or nothing to gain from the safety benefits of the drugs," Alexander said. "This new study is important in light of our study because it suggests that many individuals were exposed to increased cardiovascular risk unnecessarily."
Yet another study, led by Dr. David Graham, associate director for science at the U.S. Food and Drug Administration's Office of Drug Safety, estimated that Vioxx may have caused up to 140,000 excess cases of serious coronary heart disease. That report was published online Jan. 24 issue of The Lancet.
And within the last three days, there have been these other news developments involving cox-2 inhibitors:
- On Friday, the Securities and Exchange Commission said its informal investigation of Merck's withdrawal of Vioxx was being upgraded to "formal," meaning the SEC could issue subpoenas to company executives.
- On Saturday, The New York Times reported that Kaiser Permanente, the nation's largest managed care group, had told its pharmacies to stop dispensing Pfizer Inc.'s arthritis painkiller Bextra. Pfizer acknowledged last fall that studies showed Bextra posed an increased risk of heart attack and stroke among patients who have had coronary artery bypass surgery.
- On Monday, the consumer advocacy group Public Citizen accused Pfizer of trying to hide a study that suggested Celebrex boosted heart risks. The group renewed a request made last week that the U.S. Food and Drug Administration order Bextra and Celebrex off the market.
More information
The U.S. Food and Drug Administration has more about Vioxx.
