Pfizer Reveals Study Linking Celebrex to Heart Risks

Feb. 1–WASHINGTON — Pfizer Inc. has revealed it completed a study four years ago that links its painkiller Celebrex to a “statistically significant” increase in heart problems, bolstering demands for speedier dissemination of negative trial results.

The recent disclosure, on an industry-sponsored website, appears to contradict recent statements by the company. It is the second study known to connect Celebrex to cardiovascular troubles. Though medical experts disagree on how to interpret the newly revealed trial, they agree on this: The information should have been publicized much sooner.

“What’s a bit disturbing is that this hasn’t been published before,” said Dr. Bruce Psaty, an epidemiologist and expert on cardiovascular health at the University of Washington in Seattle who has given congressional testimony critical of the drug industry. “That’s several years where it languished, unpublished. This just speaks to the need to have clinical trials registered and reported publicly in a prompt and complete way.”

US Senator Chuck Grassley, an Iowa Republican, this month plans to introduce legislation to prod companies to make clinical trial data public.

In December, the National Cancer Institute halted a Celebrex trial because high doses of the drug were linked to 3.4 times greater risk of cardiovascular problems. Though Pfizer’s own study ended in 1999, Pfizer called the results of the institute’s study “unexpected.”

A month later, Pfizer, the world’s biggest drug company, posted its 1999 study linking Celebrex to a list of heart risks onto the clinical trials site maintained by the Pharmaceutical Research and Manufacturers of America, the industry’s main trade group. Court Rosen, a spokesman for PhRMA, as the group is known, referred all questions on the study to Pfizer.

Pfizer said it provided the Celebrex study to the Food and Drug Administration in June 2001. The company did not return calls seeking comment on the timing of last month’s public disclosure.

Sid Wolfe, health research group director at Public Citizen, a Washington-based consumer advocacy group, said he stumbled upon the Celebrex study while looking on the PhRMA website for something else. On Monday, Public Citizen renewed its call for the FDA to immediately ban Celebrex and Pfizer’s other controversial painkiller, Bextra.

While the FDA said it will “review the petition carefully,” the nation’s largest health maintenance organization — guided by outside studies — has acted more decisively. Beginning today, 6.2 million Kaiser Permanente members in California no longer will receive new Bextra prescriptions.

Kaiser is urging doctors to avoid prescribing high doses of Celebrex “until information is available to reassure our physicians that the drug is safe,” said Dr. David Campen, head of Kaiser’s pharmacy operations.

The quiet release of the 1999 Celebrex study comes amid high-profile disclosure of heart problems with such popular painkillers as naproxen, Bextra, Celebrex, and Vioxx. The worries halted clinical trials, led to Vioxx being withdrawn from the market, and raised concerns among arthritis sufferers.

Amid the flurry of activity, European and American regulators are preparing for meetings this month to weigh the risks and benefits of the entire class of so-called cox-2 inhibiting painkillers, including Bextra, Celebrex, and Vioxx.

According to Pfizer’s fourth-quarter earnings report, worldwide sales of Celebrex exceeded $3.3 billion in 2004, with $1 billion in revenue in the fourth quarter. Celebrex revenue rose by 24 percent that quarter, after Vioxx was taken off the market and Pfizer heavily advertised Celebrex. Bextra sales reached nearly $1.3 billion last year, with a 57 percent jump in fourth-quarter revenue.

Pfizer faces scores of lawsuits from angry investors and patients alleging harm from Bextra and Celebrex as well as consumer fraud allegations that claim Pfizer’s advertising minimized health risks. In December, Pfizer agreed with the FDA’s request to stop advertising both products. In addition, the Department of Justice has sought documents from the company and a coalition of attorneys general are scrutinizing Pfizer’s marketing of Bextra and Celebrex.

Public Citizen analyzed the recently posted Celebrex trial and said it indicated people taking Celebrex as a potential Alzheimer’s disease treatment had a 3.6-fold increase in serious cardiovascular events and more than doubled risk of dying from heart problems.

In that study, people took 200 mg of Celebrex twice daily, with breakfast and dinner, for 52 weeks. The study wanted to determine whether the painkiller would ease the progression of Alzheimer’s disease and gauged the long-term safety of that high dose of Celebrex in elderly, debilitated people. The drug did not slow the progression of Alzheimer’s.

The FDA approved Celebrex to reduce pain and swelling for people with osteoarthritis and rheumatoid arthritis on Dec. 31, 1998.

In a statement yesterday, Pfizer acknowledged that people taking Celebrex suffered more cardiovascular problems than those taking a placebo. The company added, however, that patients taking its drug had more medical conditions than the placebo group, potentially confusing comparisons.

“Celebrex patients were up to four times more likely to have key cardiovascular risk factors, compared to patients who received placebo. These risk factors include hypertension, diabetes, aspirin use, and previous bypass surgery,” Pfizer said. “Because of this marked imbalance in the health of participating patients, definitive conclusions about cardiovascular risk cannot be drawn from this study.”

A cardiologist who was among the first to warn about the risk of cox-2 painkillers agreed that differences in key events — heart attack, stroke, and death — were not statistically significant in the Celebrex group.

“I don’t mean to say it isn’t a worry. It’s a signal of risk,” said Dr. Eric Topol, a Cleveland Clinic cardiologist. “The fact it wasn’t published all these years is not good.”

The University of Pennsylvania’s Dr. Garret A. FitzGerald, another early critic of cox-2 inhibitors, agreed.

“While these results were far from conclusive on their own at the end of 2000, they most certainly would have heightened scrutiny of this issue by investigators and practitioners had they been in the public domain,” FitzGerald said.

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