Yesterday'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 designed not 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 on Sept. 23 to stop the trial because the drug appeared to be increasing the risk of heart attacks and strokes. Patients taking the drug for more than 18 months appeared to face about double the risk of major cardiovascular events, primarily heart attacks and strokes, compared with those taking a dummy pill.
Merck's arthritis drug Vioxx generated $2.5 billion in worldwide sales last year.
(Daniel Hulshizer -- AP)
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More Heart News
The acting director of the FDA's Center for Drug Evaluation and Research, Steven K. 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 to the incidents being reported.
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 yesterday.
Eric J. Topol, the 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." Topol was a co-author of the study that first suggested a possible hazard from rofecoxib, the generic name of Vioxx.
Although Topol said he is not sure whether his earlier analysis was enough to warrant yanking Vioxx off the market in 2001, "it was enough to address this and get the right answer. We shouldn't have to wait to get it from a study of patients with colon polyps."
That view was shared by Jerry Avorn, a physician at Harvard Medical School who is an expert on the use and marketing of prescription drugs.
"When this question came up initially, the standard response from the FDA was to hope the company would do its own study to resolve it," he said. "The FDA has not been brave enough in demanding that companies perform safety studies of this kind."
Yesterday's announcement threw into a quandary patients who were taking the drug. 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, a rheumatologist at George Washington University who serves as the 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."
Researchers have a general idea of how Vioxx may be raising the heart attack risk, although the details are not known.
The event that triggers heart attacks and most strokes is the formation of a blood clot in an artery. Clotting is controlled by a delicate seesaw of compounds that have opposing effects. Two of the more important ones are prostacyclin, which inhibits clotting, and thromboxane, which promotes it.
Prostacyclin is made primarily in cells lining the inner wall of blood vessels by an enzyme called COX-2. Blocking COX-2, which Vioxx does in its effort to stop inflammation in joints and other tissue, may have the effect of tipping the balance in favor of clot-promoting thromboxane, experts believe.
What is unclear is whether all COX-2 inhibitors have this effect -- in either a mild or more severe form -- or whether it is unique to Vioxx.
Staff writers David Brown and Rob Stein contributed to this report.