Merck & Co. said on Thursday withdrew its arthritis drug Vioxx globally after a colon cancer trial confirmed long-standing concerns the drug raises the risk of heart attack and stroke.

Merck’s shares plunged in pre-market trading after the announcement.

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

Vioxx had sales last year of $2.55 billion. They have been flat in recent years amid ongoing safety concerns.

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.

“It’s a major blow for Merck,” said Sena Lund, an analyst at Cathay Financial. “It was one of their five key drivers for future growth.”

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, have steadily grown as doctors have turned to those drugs, which have not been linked to heart attack and stroke.