Vioxx's cardiovascular side effects led Merck & Co. to take it off the market last fall, and now Bextra is off the market for similar reasons. The remaining and most popular COX-2 drug, Celebrex, will have a stern new black-box warning on its label. Vioxx, Bextra and Celebrex selectively block the Cox-2 enzyme, which triggers pain and inflammation in the body.

Cox-2 inhibitors, which began to appear in 1999, were developed to avoid the stomach irritation often caused by the older, less selective "nonsteroidal anti-inflammatory drugs," or NSAIDs.

"The FDA has sort of swung from saying there's no problem to saying everything is a problem," said Garrett FitzGerald, a University of Pennsylvania cardiologist and pharmacologist.

The latest safety action "serves the FDA's purpose, because you've got all these politicians saying, 'Great, the FDA has changed and gotten tougher,' " FitzGerald said. "But for the practitioner, it creates confusion."

Catherine J. Arnold, a pharmaceutical market analyst with Credit Suisse-First Boston, said the FDA's decision "signals a more conservative stance... and stronger efforts to demonstrate a commitment to public safety."