NEW YORK (Reuters Health) - Merck’s withdrawn painkiller Vioxx may have continued to cause blood clots and perhaps deaths even after patients dropped it, U.S. researchers said Monday.
The drug was recalled by Merck in 2004 after a colon-polyp prevention study showed it increased the risk of heart disease and death in users. But over the five years it was on the market, researchers estimate it caused nearly 40,000 deaths.
The new findings, published in the Archives of Internal Medicine, are based on data made available by Merck during multibillion-dollar litigation against the company.
They show patients taking Vioxx (also called rofecoxib) doubled their chances of having blood clots or dying in the first half-year after discontinuing treatment, confirming earlier results that hinted the effects might last up to one year.
What happens after that is still an open question, said Dr. Joseph Ross of the Yale School of Medicine in New Haven, who worked on the study.
“At this point, there isn’t evidence to suggest that patients need to discuss with their physicians whether they are at increased risk after discontinuing Vioxx more than 6 years ago,” he said in an e-mail to Reuters Health.
His co-author Dr. Harlan Krumholz, also of Yale, said the study also stokes concerns about painkillers in the same class as Vioxx -- the so-called selective COX-2 inhibitors.
When scientists first discovered these drugs, the hope was they would lower the risk of ulcers among chronic users of non-steroidal anti-inflammatory drugs, or NSAIDS, such as people with rheumatoid arthritis.
But most COX-2 inhibitors -- a subset of the NSAID category -- ran into safety issues a few years after their approval, and now only Pfizer’s Celebrex (celecoxib) remains on the U.S. market. Other NSAIDs include low-dose naproxen, ibuprofen, ketoprofen and aspirin.
In the new study, the team looked at 617 patients who had stopped taking either Vioxx or a dummy pill following more than a year and a half of use.
After six months, on average, 22 patients on Vioxx reportedly developed blood clots and 23 died. Among those taking the placebo, the numbers were six and nine, respectively, at four months.
That translates into an overall rate of deaths or blood clots of 0.11 per year after a patient drops Vioxx -- twice as high as seen in the placebo group.
“It indicates a need for more research to understand better how these drugs confer risk,” Krumholz said in an e-mail, “and whether we need to know whether people have ever taken these types of medications when we assess risk.”
“For future drug evaluation and development we need to pay attention to effects that may manifest after the drug has been discontinued,” he added. “To me, these results from the Vioxx studies about what happened to people after they stopped taking the drug may even be more important than the studies that showed risk when they were on the drug.”
Both Krumholz and Ross have consulted for the plaintiffs in lawsuits against Merck. Their co-authors also report having received fees from several pharmaceutical companies.
Merck did not respond to a request for comment on the new findings.
Dr. John Baron of Dartmouth Medical School in Lebanon, New Hampshire, who oversaw the colon-polyp study for Merck, said most experts now believe the increased risks are a common trait among COX-2 inhibitors.
He said a new study testing all the drugs in the class is in the works.
“The most important analysis will be the combined analysis that will give more information regarding the individual drugs as well as presumed class estimates,” he told Reuters Health.
SOURCE: link.reuters.com/van89q Archives of Internal Medicine, online December 13, 2010.