Analysis: Merck knew Vioxx risk four years ago

By Linda Loyd
Knight Ridder Newspapers

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The analysis, by Peter Juni and colleagues at the University of Bern, looked at results from 18 Vioxx studies, all sponsored by Merck, that showed that 41 of about 11,000 Vioxx users by late 2000 had suffered heart attacks, twice the rate of those receiving a placebo or other painkillers.

The study, paid for by the Swiss National Science Foundation, analyzed 18 randomized controlled Vioxx trials and 11 related observational studies.

The results were published online by the British journal The Lancet. They were based on data obtained primarily from the Food and Drug Administration (FDA).

Stock price falls

When Merck withdrew Vioxx on Sept. 30, after a company-sponsored study found a doubling of the risk of heart attack and stroke in users after 18 months, Merck said the data was "unexpected."

Merck shares plunged this week after a media report Monday said documents showed the pharmaceutical giant hid or denied evidence for years that the arthritis drug caused heart problems.

Merck said in a press release yesterday that it has been "vigilant in monitoring and disclosing the cardiovascular safety of Vioxx" and "we absolutely disagree with any implication to the contrary."

The Swiss researchers concluded the heart-attack risk was as great in patients taking 12.5-milligram and 25-milligram doses as the 50-milligram Vioxx dose. "The increased risk appears not to be dose-dependent," Juni said.

Researchers said the increased rate of heart attacks occurred in patients who took Vioxx less than six months and in those who took it longer. "We don't have evidence to suggest the length of treatment influences increased risk," Juni said.

In a scathing editorial, Lancet editor Richard Horton faulted Merck for "astonishing failures" in monitoring the post-marketing safety of its drug. Horton also criticized the FDA for "lethal weaknesses" in regulatory oversight.
 
The Lancet had commended Merck a few weeks ago for "acting promptly" to withdraw Vioxx, but said yesterday "our praise was premature."

"With Vioxx, Merck and the FDA acted out of ruthless short-sighted and irresponsible self-interest," the editorial says. "It's hard to see how Merck's chief executive officer, Raymond Gilmartin, can retain the confidence of the public, his company's most important constituency."

Analysis disputed

In its response, Merck said that data used in the Lancet analysis "are not new and are essentially consistent with the results from the combined analyses of randomized controlled clinical trials that Merck published in 2001."

What's more, Merck said, the Lancet's analysis is "not as comprehensive as our combined analyses because it fails to include several studies, including two large placebo-controlled studies that are publicly available and were summarized in the U.S. prescribing information for Vioxx."

Prudential Equity Group analyst Tim Anderson said that the Lancet's report "plays into the hands of plaintiffs' attorneys" and "has the ability to bolster their case against the company." However, Anderson said lawyers suing Merck must prove the company was negligent and knew about the Vioxx risks, and that the drug played a role in causing heart attacks or strokes.

Proving causation — that Vioxx caused people's heart problems — will be "much harder to achieve," Anderson said. "We do not think at this time, at least, that the company's ultimate liability will sum to fen-phenlike proportions," referring to the $16.6 billion Wyeth has set aside to pay for liability from its recalled diet drugs.

Background on Merck's stock losses this week was provided by Seattle Times archives.