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Merck's Vioxx Under Fire Again

Robert Steyer

A study published in the New England Journal of Medicine suggests that Vioxx heightens the risk of cardiovascular problems faster than Merck (MRK Quote) says it does.

The study, which contains several caveats, raises questions about Merck's assertion that cardiovascular risks were statistically significant only after patients took the arthritis drug for more than 18 months. Several critics have challenged Merck's conclusions about Vioxx, which was removed from the market in September 2004.

Vioxx therapy "was associated with an increased frequency of adverse cardiovascular events among patients with a median treatment of 7.4 months' duration," says the article, published Wednesday online by NEJM. The article uses data from a Merck-sponsored study that was halted after the company withdrew Vioxx.

The article was prepared by researchers at several British medical schools and a U.K. hospital. Their work was sponsored by Oxford University and an education grant from Merck.

When Merck withdrew Vioxx, it acted on results of another company-funded clinical trial, which assessed if Vioxx could reduce certain colon polyps. The trial was known by the acronym APPROVE. Merck said an independent safety monitoring board recommended stopping APPROVE due to higher risks of cardiovascular problems in patients who took Vioxx for more than 18 months.

Authors of the NEJM article used data from a study called VICTOR, which was checking if Vioxx could reduce the recurrence of colon cancer. Researchers point out that their work was hampered by "the small number of events available for analysis" and the 7.4-month median exposure to Vioxx.

"However, our findings suggest an increased risk" of dangerous cardiovascular side effects for Vioxx patients compared with placebo recipients, they say. There was no significant difference in heart-related deaths between the groups.

Researchers examined "cardiovascular thrombotic events" during the study period and for two years after VICTOR was halted. The median treatment before such events, including heart attack, stroke and blood clots, was 157 days for Vioxx patients and 195 days for placebo patients.

The relative risk of a dangerous side effect occurring during treatment, or within 14 days of treatment, was more than double for the Vioxx group. Relative risk compares the percentage of side effects among Vioxx patients with the side-effect percentage for placebo-takers.

The VICTOR trial was designed to test 7,000 patients. Half were to have received Vioxx or a placebo for 24 months, and half were to have received the Merck drug or a placebo for 60 months. When the test was halted, only 2,434 patients were enrolled, and only 4% had received Vioxx for more than two years.

Although the NEJM article was subject to a publication embargo, a Merck executive told analysts on July 23 that the findings were old news. "I think we indicated many times that this is but one study," said Graeme Bell, executive director of investor relations, responding to an analyst's question during Merck's second-quarter earnings presentation.

"You know the history in terms of [VICTOR] being stopped prematurely, and that such data, in and of itself, has been available" to people and their lawyers, Bell said. This data has been used by plaintiffs in many trials, he added.

"We feel that one data point in and of itself can draw no conclusion whatsoever," Bell said. "We remain steadfast based on the scientific evidence relating to" the results of the APPROVE trial.