2002 Vioxx Study Submitted to FDA Showed Possible Heart Risks

A 2002 study indicated that older patients taking Merck's COX-2 inhibitor Vioxx might be at higher risk for developing cardiovascular problems, but an FDA analysis of the study's data found no correlation, the Chicago Tribune reports. The studies were designed to determine whether Vioxx could reduce the cognitive decline associated with Alzheimer's disease.

In March 2002, preliminary data showed that 29 patients taking Vioxx in the study had died, compared to 15 in the placebo group. FDA examined the preliminary results in a 2002 memo and a December 2004 update of the Alzheimer's studies. According to the 2004 report, 41 patients taking Vioxx had died during the trial, compared with 23 in the placebo group. FDA scientist Lourdes Villalba, an author of the study, said there was no one trend that was apparent in the patient deaths, except that patients taking Vioxx had more fatal cardiovascular events. FDA reports "documented a notable increase in deaths among Alzheimer's patients taking Vioxx," the Tribune reports.

In a March 2002 report, FDA suggested that "fluid retention, edema and hypertension may play a role in the different cardiovascular safety profile" of Vioxx, but the information was omitted in testimony by Merck CEO Raymond Gilmartin in November 2004. He also testified that "there was no difference in cardiovascular events rates in these two (Alzheimer's) trials." Vioxx was later voluntarily withdrawn from the market last Sept. 30 after a different study showed an increased risk of heart attack and stroke.

Gurkirpal Singh, director of the postmarketing drug surveillance program at Stanford University, said that the studies have not been disclosed previously and that he was surprised when he saw them on an FDA Web site. "You would think physicians would want to know Merck had evidence indicating that patients taking Vioxx in two clinical studies were twice as likely to die as those taking placebo. It's a very important finding," he said.

Singh said patients in the Alzheimer's trial taking Vioxx may have had higher mortality rates because the medication increased rates of hypertension, fluid retention around the heart and congestive heart failure but not rates of heart attack and stroke. Singh said, "They were dying before they got a heart attack or stroke." Dr. Curt Furberg, a member of the FDA panel that will examine the safety of COX-2 inhibitors next week, said the "studies show a substantial increase in mortality associated with Vioxx. This should have been a very strong signal to Merck that they had real problems with this drug" (Graham, Chicago Tribune, 2/10).