Merck & Co. (MRK) Thursday pulled its arthritis drug Vioxx off the market because it increases the risk of heart attack and stroke, a move that sent its shares plunging, erasing $25 billion of its market value.

Merck said it is withdrawing the drug following data from a new three-year trial of Vioxx, designed to evaluate the effectiveness of the drug's standard 25 milligram dose in preventing recurrence of colorectal polyps. Such polyps often become cancerous.

"In this study, there was an increased relative risk for confirmed cardiovascular events, such as heart attack and stroke, beginning after 18 months of treatment in the patients taking Vioxx compared to those taking placebo," Merck said in a release.

Vioxx, used by two million people around the world, accounts for 10 percent of Merck's annual sales.

A recent study by the Food and Drug Administration (search) suggested patients taking Vioxx faced a 50 percent greater risk of heart attacks and sudden cardiac death than those taking Pfizer Inc.'s (PFE) rival Celebrex (search) treatment.

The withdrawal of the drug casts a cloud over an entire class of widely used arthritis and pain drugs known as COX-2 inhibitors (search). "This has implications for all members of this class," said Dr. Garret FitzGerald, chairman of the Department of Pharmacology at the University of Pennsylvania.

Merck said that in a colon cancer trial, patients who took Vioxx for three years faced twice the risk of cardiovascular events, such as heart attack and stroke, as patients taking a placebo.

"Patients who are currently taking Vioxx should contact their health care providers to discuss discontinuing use of Vioxx and possible alternative treatments," it said.

Concerns over the drug's side effects have been building in recent years after several studies showed risks attached to it. Other drugs in the same class, including Celebrex and Bextra and Novartis AG's Prexige, have so far not shown the same dangers.

"This is a very significant negative for Merck. Not only is this a nearly $3 billion drug, but it calls into question the future of one the key drugs in its pipeline, Arcoxia," said Scott Henry, an analyst at Oppenheimer & Co.

Arcoxia (search), which is similar to Vioxx, is sold outside the United States but has not yet been approved by the FDA because of concerns about heart and stroke risk. Some analysts had expected the agency to rule on Arcoxia by late October.

Merck is already struggling with slowing earnings growth and faces the loss of patent protection for its biggest-selling drug, cholesterol fighter Zocor, in 2006.

Despite the setback, Merck Chairman and Chief Executive Raymond Gilmartin said he had no intention of resigning.

Merck is already gearing up for lawsuits over Vioxx. "We have substantial defenses in these cases and will defend them vigorously," said Kenneth Frazier, Merck's general counsel.

Merck shares fell 25 percent on the New York Stock Exchange (search). Shares of Pfizer, which sells two rival arthritis drugs, edged higher.

Merck had expected Vioxx to help restore the company's earnings growth when the drug was launched in 1999, but its sales have been hurt by clinical trial data showing it increased the incidence of blood clots tied to strokes and heart attacks.

Meanwhile, sales of Pfizer Inc.'s similar drugs, Celebrex and Bextra (search), have steadily grown as doctors have turned to those drugs, which have not been linked to heart attack and stroke.