Studies pose new questions on entire class of pain drugs

Two studies released Monday have turned up new evidence that all of the popular arthritis painkillers known as COX-2 inhibitors may put users at greater risk of heart attacks and strokes.

The first of the two papers published online by the journal Circulation found that patients who had had heart bypass surgery and were taking Pfizer Inc.’s Bextra and another experimental COX-2 inhibitor were three times more likely to have strokes and heart attacks than patients taking a placebo. The statistically significant tripling of the risk showed up when researchers combined the results of two earlier studies involving more than 2,000 people in a statistical technique called meta-analysis.

A second study found that when mice that are genetically prone to hardening of the arteries were treated with a COX-2 drug and an aspirin substitute, their condition worsened rather than improving, as researchers had anticipated.

Lead researcher Garret A. FitzGerald of the University of Pennsylvania said the two studies led him to conclude that the entire class of drugs poses a risk. He also said an upcoming clinical trial proposed by Pfizer, the maker of Celebrex, to test whether that drug may help patients with heart disease, should not go forward.

The latest bad news for makers and users of COX-2 drugs comes a month before the Food and Drug Administration is scheduled to hold an unusual three-day hearing, Feb. 16-18, of two advisory panels to consider safety issues that have arisen around the class of drugs.

Planning for the meeting began in the fall after Merck & Co. took its blockbuster COX-2 drug Vioxx off the market after a study it sponsored found heightened cardiovascular risk in volunteers taking the drug. Since then, federal officials have been formally reviewing the risks of using Celebrex in more than 40 federally sponsored studies into other potential uses of the drug. Both Celebrex and Bextra remain on the market, but in increasingly limited use.