Cardiologist questions safety of Vioxx-like painkillers

Without clearer evidence of the safety of painkillers similar to Vioxx, doctors should avoid prescribing them for patients at risk of heart disease, according to an editorial by a prominent cardiologist posted on the Internet yesterday by the New England Journal of Medicine.

Vioxx was withdrawn from the market last Thursday after a definitive study showed the drug doubled the risk of heart attack and stroke when taken daily for more than 18 months. Other studies, as far back as 2001, had suggested possible heart problems with the drug.

But there have been no definitive studies of the potential heart risk of taking the similar drugs Celebrex and Bextra, and doctors disagree about whether patients should take those drugs. Pfizer Inc., which makes Celebrex and Bextra, maintains that both drugs are safe if taken at the doses approved by the US Food and Drug Administration. The widely prescribed drugs are known as Cox-2 inhibitors, and some evidence suggests they are less harsh on the stomach than cheaper pain relievers such as aspirin and ibuprofen.

The debate about the drugs' safety is raging as doctors seek alternatives for 2 million patients worldwide who were taking Vioxx. Patients have flooded doctors' offices to get new prescriptions. The drugs are commonly taken for relief of chronic pain from arthritis.

The FDA is reviewing data on the Cox-2 inhibitors, but has given no indication of whether or when it will provide additional guidance for doctors and patients. The FDA did not respond to requests for comment yesterday.

In the absence of that advice, Dr. Garret A. FitzGerald, a professor of cardiovascular medicine at the University of Pennsylvania School of Medicine, says doctors should be cautious. FitzGerald, who has studied Cox-2 inhibitors, said there are enough hints of heart risks with these drugs that manufacturers should have to prove anew that their drugs are safe. He said he believes the drugs all suppress a hormone-like substance in the body that protects against heart disease.

The withdrawal of Vioxx ''shifts the burden of proof," he said. ''It is extremely likely," he said, that the heart risks are common to all Cox-2 inhibitors.

But Dr. Lee Simon, a rheumatologist at Beth Israel Deaconess Medical Center, who studied the Cox-2 inhibitors while working at the FDA from 2002 to 2003 and has consulted for Pfizer, said he did not see any evidence suggesting that all the Cox-2 inhibitors cause cardiovascular problems.

''Given the data, I'm uncomfortable painting the brush across the board," he said. The drugs appear to work slightly differently and to cause different side effects, he said, with Vioxx and Bextra causing hypertension and swelling at high doses, for example, but not Celebrex.

Both Simon and FitzGerald, however, agreed that a study of Bextra in patients undergoing coronary bypass surgery did show a higher incidence of heart attacks and strokes. And Simon noted that a new Cox-2 inhibitor, not yet approved in the United States, carries a warning about cardiovascular risks when it is marketed abroad. ''There's no question we need more data" about cardiovascular risks, Simon said.

All of the drugs have been marketed as gentler on the stomach than aspirin or ibuprofen. But evidence is conflicting there as well. Both doctors suggested that their colleagues should reevaluate whether patients need a Cox-2 inhibitor because of previous problems with stomach bleeding or ulcers.

One alternative is to prescribe ibuprofen or naproxen along with a drug to protect the stomach.

Yesterday, an official at Pfizer said the company was conducting a five-year study similar to the one that led Merck & Co. to pull Vioxx off the market last week. The study is testing whether Celebrex prevents recurrence of colorectal polyps. The results will not be available for another three years, said Dr. Mitch Gandelman, vice president of Pfizer's worldwide medical group, but he said doctors monitoring the patients in the study had so far seen no significant heart problems.

''We stand behind the drugs," he said. ''And we will continue to monitor the cardiovascular safety of our products."