BOSTON (AP) -- Plavix, a heart drug recommended by medical groups as an easy-on-the-stomach substitute for aspirin, instead showed a much higher risk of recurrent ulcers in a small but provocative study.

The study could upend the treatment guidelines for tens of thousands of Americans who must take anti-clotting drugs for their hearts but are prone to gastrointestinal problems.

"These are very surprising findings, because the conventional wisdom is that Plavix is a GI-safe medicine -- or I should say `has been' a GI-safe medicine," said Dr. Byron Cryer of the University of Texas Southwestern Medical School and Veterans Affairs hospital in Dallas.

He said he has stopped prescribing Plavix to his own patients who have a high risk of ulcers, but believes the drug is still OK for others. He said the U.S. guidelines for Plavix should be re-evaluated in light of the findings.

He wrote an editorial to accompany the study, published in Thursday's New England Journal of Medicine.

The findings, reached by Hong Kong researchers, come as a surprise because Plavix was gentle on the stomach in previous testing. However, the patients in earlier research had a normal ulcer risk overall. This study was the first one to look at patients who had already had an ulcer.

An estimated 50 million Americans take aspirin, the inexpensive old standby, to ward off heart attacks and strokes. But aspirin can cause bleeding, ulcers or other stomach problems in perhaps a third of users.

Plavix is recommended as an alternative by the American Heart Association and American College of Cardiology. It is aggressively marketed on TV by Sanofi-Aventis and Bristol-Myers Squibb. It was the 12th best-selling prescription drug in the United States in 2003, with $2.2 billion in sales, according to IMS Health, an industry consultant.

Sanofi-Aventis spokeswoman Leslie Hare disputed the latest findings. She said Plavix has been used by 41 million people around the world, and its safety and effectiveness have been well-established.

In the one-year Hong Kong study, 320 patients with healed ulcers were given either aspirin or Plavix. The aspirin patients also took an acid-blocking drug to help protect their stomachs.

In the Plavix group, bleeding ulcers came back in 13 patients, or 8 percent. Among those who took aspirin, only one had another ulcer, or less than 1 percent.

"I'm as surprised as you are," lead researcher Dr. Francis Chan said. He said the rate of recurring ulcers for those on Plavix was "totally unacceptable."

It is unclear why Plavix seems to aggravate ulcers. It may simply allow them to bleed more, since it interferes with blood clotting. But it may also deprive the wound of substances that promote healing, researchers said.

Dr. Sidney Smith, a former president of the American Heart Association who helped develop the U.S. Plavix guidelines, said the Hong Kong study is interesting, but not big enough or diverse enough.

"It'd be premature to say how this study might affect the guidelines," he said.

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