The blockbuster arthritis drug Vioxx was taken off the market Thursday by Merck & Co. after a study confirmed simmering concerns that it significantly raised the risk of heart attack and stroke. More than 2-million people take Vioxx worldwide, making this the largest voluntary drug recall in history.
Merck said it received new information last week showing that people who used the drug for more than 18 months had nearly twice as many serious cardiovascular problems as those on a placebo. By Tuesday, the company had told the Food and Drug Administration it planned to withdraw the drug.
"We believe it would have been possible to continue to market Vioxx with labeling that would incorporate these new data," said Merck president Raymond Gilmartin. "However, given the availability of alternative therapies, and the questions raised by the data, we concluded that a voluntary withdrawal is the responsible course to take."
FDA officials said they would begin additional study of three other painkillers in the class called Cox-2 inhibitors, which were hailed as near-miracle drugs when they came on the market in the late 1990s. The officials said the other Cox-2 drugs have not been associated with the same dangers of stroke and heart attack, but acknowledged that no patients using them have been followed for 18 months, as was the case with Vioxx.
Although Vioxx was aggressively marketed after it won FDA approval in 1999 and has been used widely, with more than 84-million prescriptions written, serious health concerns were reported soon after it became available. The FDA required additional warnings to the drug's label in 2002, and several months ago received the abstract of another report describing heightened cardiac and stroke risks with Vioxx. FDA officials said they were studying those results when Merck contacted them earlier this week.
Patients who said they had been harmed by Vioxx had filed more than 200 lawsuits before Thursday's announcement. Many of the cases have been consolidated into two major lawsuits in Los Angeles and New Jersey.
Merck officials stressed that there were no more than the expected number of deaths among the patients taking Vioxx in the new study, and they knew of no deaths that should be attributed to the drug. But the company, long one of the industry's biggest and most respected, was clearly concerned about potential lawsuits.
"We have substantial defenses in these cases and will defend them vigorously," said Kenneth Frazier, Merck's general counsel.
Vioxx is the first prescription drug to be withdrawn since 2001, when the cholesterol-lowering drug Baycol was taken off the market.
Thursday's announcement rekindled the debate over whether the FDA has been sufficiently aggressive in monitoring drug safety. The clinical trial that found the increased danger of cardiovascular disease in patients taking the painkiller was not designed to assess the drug's safety, but to determine whether Vioxx protects against the recurrence of potentially cancerous intestinal polyps.
An independent panel monitoring the study advised the company Sept. 23 to stop the trial because the drug appeared to be increasing the risk for heart attacks and strokes. Patients taking the drug for more than 18 months appeared to face about double the risk for a major cardiovascular event, compared to those taking a dummy pill.
The acting director of the FDA's Center for Drug Evaluation and Research, Steven Galson, said the agency had been "closely monitoring" reports of serious side effects from Vioxx through its national adverse event reporting system. But he also said that because so many Americans suffer heart attacks and strokes, it has been difficult to pin down how Vioxx might be related.
Because the FDA and Merck had been aware for some time of the reports of heightened health risks with Vioxx, the agency came in for harsh criticism Thursday.
Eric Topol, head of cardiology and chief academic officer of the Cleveland Clinic, called it "the right decision about three years too late."
"This is the sort of thing that Merck should have studied earlier, but they were too busy refuting the warning signs," said Topol, a co-author of the study that first suggested a hazard from Vioxx.
Thursday's announcement threw patients who were taking the drug and their doctors into a quandary. Merck officials said about 1.3-million Americans were taking Vioxx at any given time over the past year.
"A lot of patients are upset," said Patience White, chief public health officer for the Arthritis Foundation. "I've had patients calling me all day saying, "What do I do? Do I really need to stop taking this drug?' I say, "Yes, you do,' and talk to them about other options."