MONDAY, Nov. 13, 2006 (HealthDay News) -- Researchers on Monday reported results of the first published studies of Arcoxia, a cox-2 inhibitor drug that may be poised to replace Merck's disgraced blockbuster, Vioxx.
Rates of heart attack, stroke or death in patients with arthritis were the same regardless of whether they took Arcoxia (generic name etoricoxib) or the traditional non-steroidal anti-inflammatory drug diclofenac, the researchers said at an American Heart Association press conference in Chicago.
"Relative to the most widely used agent in the world, etoricoxib did not increase the risk of any thrombotic cardiovascular event over a three-year period," said Dr. Christopher Cannon, of Brigham and Women's Hospital in Boston and lead author of a paper appearing in the journal The Lancet.
But critics complain that the comparison is a skewed one, because diclofenac is known to raise heart risks. It would have been much better to have compared it to Aleve (naproxen), experts told the Associated Press.
The Lancet paper was being released early to coincide with a presentation Monday at the heart meeting. That presentation, in turn, coincides with a presentation at a meeting of the American College of Rheumatology, in Washington, D.C.
According to a news release issued by Merck on Friday, the company is seeking approval for two doses of the drug: 30 milligrams once daily and 60 mg once daily. The drug is already available in 62 countries.
These doses are lower than those seen in the trial (60 mg and 90 mg), noted Dr. Timothy Gardner, chairman of the AHA committee on scientific sessions program, and medical director of the Center for Heart and Vascular Health at Christiana Care Health Services in Wilmington, Del.
"This may be related to concern Merck has," Gardner added.
A statement released by the AHA said, "Current evidence indicates that selective cox-2 inhibitors have important adverse cardiovascular effects including increased risk for heart attack, stroke, heart failure and hypertension." The statement advised that only patients with no other appropriate alternatives should use cox-2s and, even then, the drugs should be used "in the lowest dose and for the shortest duration necessary."
The anti-inflammatories known as non-steroidal anti-inflammatory drugs (NSAIDs) have been a mainstay of treatment for arthritis but are complicated by the fact that they increase the risk for gastrointestinal bleeding.
Arthritis affects some 46 million people in the United States alone, Cannon said.
The newer cox-2 inhibitors such as Vioxx and Celebrex don't have the problem of GI bleeding but recently were found to increase the risk of cardiovascular events, including heart attack.
"Overall, this was about a 40 percent increase in cardiovascular events seen with similarity across different agents," Cannon said.
As a result, Vioxx and Bextra were pulled from the market in 2004 and 2005, respectively. Pfizer's Celebrex is the only cox-2 inhibitor left on the market.
The new paper contains pooled data from three other studies that, together, involved 34,701 people with osteoarthritis or rheumatoid arthritis. Participants, located in 46 countries, were randomly assigned to receive either Arcoxia (60 mg or 90 mg daily) or diclofenac (150 mg daily) for an average of 18 months.
The study was funded by Merck.
The rate of cardiovascular problems was similar for both treatment groups, as was the rate of life-threatening upper GI events. The overall rate of upper GI events, however, was lower in those taking etoricoxib.
The development of congestive heart failure was rare overall but more common in the 90 mg Arcoxia group. Hypertension was also higher in individuals taking both doses of this drug.
On the other hand, liver function abnormalities and other clinical GI events were more common in the diclofenac group.
Overall, a little more than half of each group discontinued their medications, citing side effects as the reason 20 percent of the time.
"We have an answer to one of two major questions, that an increase in cox-2 selectivity itself compared to a traditional agent does not increase the risk of cardiovascular events," Cannon said.
"We have to take this at face value and conclude that this particular drug does not have a high-risk profile," Gardner said.
But many other questions remain, including whether the anti-platelet effect of naproxen gives it a lower risk profile than the cox-2 agents, Cannon said.
The future of cox-2 inhibitors was just one big-business drama being played out at the AHA meeting, which, with some 25,000 attendees, is considered the Super Bowl of medical meetings.
This weekend, the AHA forbade Pfizer from making a presentation on its new cholesterol drug torcetrapib, which some say may be the next Lipitor. According to an article in the Newark Star-Ledger, Pfizer was scheduled to present data on Wednesday but was told not to because the company put out a press release ahead of the scheduled presentation. The drug apparently raises good cholesterol while lowering bad cholesterol but also raised blood pressure.
More information
For more on cox-2s, visit the U.S. Food and Drug Administration.
