Vioxx: Downfall of a Superdrug
By: Source: AARP Bulletin Today Date Posted: 2004-10-05 13:38:00-04:00
The cover of Merck's 1999 annual report features a man of perhaps 60 sending a golf ball aloft, the club swung over his left shoulder. Beside him are the words "Vioxx: Our biggest, fastest and best launch ever." In Vioxx's first seven months, the report notes, U.S. doctors wrote 5 million prescriptions for the painkilling drug.
But what began as a success story ended last month as a cautionary tale when Merck, faced with new data from a study that found Vioxx users doubled their risk of heart attack and stroke, abruptly pulled the drug from the world market. Days later, the Wall Street Journal reported on an analysis—never made public—by a safety official at the U.S. Food and Drug Administration. The study, examining data on 1.4 million Kaiser Permanente members, drew this conclusion: More than 27,000 heart attacks and sudden cardiac deaths might have been prevented if American Vioxx users had instead taken Celebrex, a competing drug.
Tens of millions of people around the world have used Vioxx, which last year accounted for more than 10 percent of Merck's revenue. The drug was approved to treat arthritis and acute pain. "Our phones are ringing off the hook," Cheri Rockhold Schmit, pharmacist at Medicap Pharmacy in Ames, Iowa, said shortly after Merck's announcement. "They want to know can they stop taking it, should we call their doctor and get them switched to something else."
Doctors say it's safe to stop taking Vioxx abruptly. They point to several alternatives for treating pain and inflammation—many cheaper than Vioxx and most just as effective. These include the older and less pricey nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen.
Some experts urge patients to look at the Vioxx revelations as a cue to review with their physicians the benefits and risks of all these medicines. "What we're telling patients and our prescribers is that people should only take them if they really need them," says Eric L. Matteson, M.D., a rheumatologist at the Mayo Clinic in Rochester, Minn.
Vioxx was the second product, after Pfizer's Celebrex, in a relatively new subclass of NSAIDs known as COX-2 inhibitors to go on sale. Merck's aggressive promotional campaign quickly boosted Vioxx into the top 20 U.S. drugs. It has been among the drugs most heavily advertised to doctors and patients alike.
Though no more effective than other NSAIDs, the new drugs were widely heralded as less likely to cause gastrointestinal bleeding than traditional anti-inflammatories such as aspirin and ibuprofen. An early trial proved this advantage in Vioxx. But while Celebrex may also be gentler on the stomach, as many clinicians maintain, clinical trials have yet to establish this to the satisfaction of the FDA.
As for blood-clotting events like heart attack and stroke, earlier research had suggested that Vioxx poses a much greater risk than Celebrex. "Millions of people have been exposed [to Celebrex], and you're not seeing the same sorts of things [as with Vioxx]," says Arthur Kavanaugh, M.D., a rheumatologist at the University of California School of Medicine in San Diego.
Still, some aren't ready to conclude that heart attack and stroke risk is confined to Vioxx until other COX-2s, including several yet to come to market, have been studied for longer periods of time and in patients at high risk for heart disease. Two commentaries in the New England Journal of Medicine condemn the FDA for not ordering such studies and suggest that the mechanism in Vioxx that causes vascular problems could extend to other COX-2s.
Pfizer itself has announced a major study to further test Celebrex's cardiovascular safety.
Though the news about Vioxx surprised many patients, debate about its heart safety began among medical researchers not long after the drug hit the market. Cardiologists from the Cleveland Clinic published an analysis in 2001 showing that the clinical trial that demonstrated Vioxx's ability to lower chances of bleeding also revealed a fivefold increase in heart attacks among Vioxx versus naproxen users. Several observational studies reinforced the finding. But Merck argued that Vioxx only appeared to promote heart attacks because naproxen, in comparison, protected against them.
In 2001 the FDA required Merck to add a warning of possible heart effects to the Vioxx label and cited the company for minimizing cardiovascular risks in some of its promotions. Among these was a May 2001 press release headlined "Merck Confirms Favorable Cardiovascular Safety Profile of Vioxx." In its warning letter to Merck, the FDA called the claim "simply incomprehensible."
While the spotlight may be on Vioxx at the moment, Marie Griffin, M.D., professor of preventive medicine at Vanderbilt University Medical Center, says all pain-relieving drugs have known risks with prolonged use. "Not only can they still cause ulcers, but all these drugs, including the older NSAIDs, can cause high blood pressure," a fact she says is "underappreciated" by many physicians. And each drug's effectiveness varies with the individual.
"For people who aren't getting much benefit," she says, "why subject yourself to the side effects?"
Katharine Greider is a writer in New York City.
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