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Study Finds Heart Disease Among Thousands of Patients Taking Vioxx

Posted on: Tuesday, 25 January 2005, 00:00 CST

Jan. 25--CHICAGO -- Two months after federal drug officials sought to delay release of a study linking the painkiller Vioxx to heart attack, the results were published Monday by the British medical journal Lancet, suggesting the drug may be connected to tens of thousands of deaths.

Further fueling the controversy surrounding drug safety in the United States, the American journal Archives of Internal Medicine joined a growing chorus of experts calling for a major overhaul of the way the U.S. Food and Drug Administration approves and monitors new drugs.

"The FDA has become a little bit too beholden to the drug companies and is either unwilling, afraid or unable to get them to do the safety studies that need to get done once there's a signal that there may be a problem," said Dr. Jerry Avorn of Harvard, who co-authored an editorial in Tuesday's issue of the Archives.

The Lancet study, conducted by FDA scientist David Graham, estimates that as many as 140,000 Americans may have developed serious heart disease as a result of taking Vioxx. The disease is fatal to about 44 percent of patients, he noted.

Graham, associate director for science in the FDA's Office of Drug Safety, said his supervisors tried to suppress his findings in November, shortly before he was to testify about Vioxx before a congressional committee. Although parts of his study already have been made public, acceptance by a peer-reviewed journal validates the findings after the FDA questioned Graham's methods.

The FDA finally granted approval for Graham to submit his analysis for publication Jan. 3 after coming under pressure from several congressmen. The study was based on a review of 1.4 million patient records at the California health maintenance organization Kaiser Permanente.

Vioxx's manufacturer, Merck & Co., withdrew the FDA-approved drug from the market in late September after a study showed it significantly increased the risk of heart attacks when compared to a placebo.

But a Merck spokesman on Monday disputed Graham's findings. "An estimate of harm from Vioxx is speculation," said Christopher Loder. "Determination of whether Vioxx was responsible for any patients' (heart attack) or stroke can only be made on a case-by-case basis."

Since the withdrawal of Vioxx, debate over the agency's effectiveness in monitoring drug safety has continued unabated, leading many critics to call for significant reforms.

"The FDA had responsibility for regulating this drug, and they didn't do what they should have," Graham said Monday in a telephone interview. "I believe the FDA ... views industry as its client and not the public, and that what happened with Vioxx is an example of that."

With the exception of a labeling change in 2002 that referred to potential heart risk, Graham said, "the FDA allowed Vioxx to be marketed extensively without effectively dealing with the risk or informing consumers."

The latest findings come as a Senate committee investigates whether the FDA failed to adequately protect the public by allowing Vioxx to be marketed widely in view of its potential dangers. The Institute of Medicine, a division of the National Academy of Sciences, is studying whether the FDA's process for approving new drugs and monitoring their safety afterward is basically flawed. A number of congressional leaders are introducing or planning bills designed to strengthen the regulatory process.

The FDA has set a three-day public meeting for Feb. 16-18 to discuss the overall "benefit-to-risk" assessment of other Cox-2 inhibitors in the same drug class as Vioxx, including the Pfizer drugs Celebrex and Bextra, as well as non-steroidal anti-inflammatory medications such as Aleve and Naprosyn.

Some critics say the agency should act now to pull the Cox-2 inhibitors. On Monday the consumer watchdog group Public Citizen formally petitioned the FDA to immediately pull Celebrex and Bextra from the market.

"If a drug offers no unique benefit compared to other drugs for treating the same problem (in this case arthritis and pain) but subjects patients to unique risk, it must be removed from the market," a 12-page petition from Public Citizen says.

The FDA wouldn't comment Monday on the petition; it also would not discuss the journal reports and editorial in view of the pending review by the Institute of Medicine.

The Archives editorial accompanied several studies about Vioxx and other Cox-2 inhibitors, including one in which an international team of scientists found that Vioxx appears to pose a risk to the heart by raising blood pressure.

The study, which involved patients from seven countries with type 2 diabetes, hypertension and osteoarthritis, showed that Vioxx significantly increased blood pressure compared with Celebrex, another Cox-2 drug, and the anti-inflammatory drug naproxen.

Another Archives study found that mass marketing of Vioxx to the public has led to doctors prescribing it to many people who would benefit equally from older, cheaper medications.

Drugs such as Aleve and Advil are as effective at relieving pain as Vioxx but carry a greater risk of stomach bleeding. But many patients are not at risk for bleeding problems and can safely use the other drugs, said Dr. G. Caleb Alexander of the University of Chicago, who co-authored the article with Stanford University's Dr. Randall S. Stafford.

They found, however, that in 2001 7.6 million patients, or 40 percent of those at very low risk of bleeding, were prescribed Vioxx. In 2000 Vioxx was the most heavily advertised direct-to-consumer drug with expenditures of $161 million.

"There at two primary concerns with the overuse of this medicine in patients that don't stand to benefit," Alexander said. "The first is the potential adverse health consequences associated with the use of this class of medicines and the second is the cost of the medicines. These medicines on average cost 10 to 15 times that of things like ibuprofen and naproxen."

By Ronald Kotulak and Judith Graham. Chicago Tribune correspondent Bruce Japsen contributed to this report.

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MRK,

Source: Chicago Tribune

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