Stent patients who take the blood thinner Plavix along with certain heartburn drugs may face a greater risk of heart attack, stroke and other dangerous events, according to a study released Tuesday.

Researchers found that patients who were taking Plavix with popular prescription heartburn drugs, including AstraZeneca PLC's Nexium, were significantly more likely to be hospitalized for a heart attack, stroke, chest pain or a coronary artery bypass operation than those who took Plavix alone.

The study followed more than 14,000 patients from 2005 to 2006 in a database kept by pharmacy benefits manager Medco Health Solutions Inc.

Nexium and other proton pump inhibitors, like Wyeth's Protonix, are used to treat chronic heartburn, in which stomach acids come back up the esophagus, causing pain and inflammation. Doctors frequently prescribe these drugs to patients on Plavix because the blood thinner has been linked to a higher risk of ulcers.

Plavix, or clopidogrel, is the second best-selling drug in the world, with global sales of $7.3 billion in 2007. It is marketed by Bristol-Myers Squibb Co. and Sanofi-Aventis SA.

Heartburn drugs were the fourth best-selling class of drugs last year, with sales of $25.6 billion, according to IMS Health.

Medco said 40 percent of patients in its study were taking the prescription heartburn medications. The company's chief medical officer, Robert Epstein, said that if over-the-counter medications like AstraZeneca's Prilosec were included, the percentage would likely be even higher.

Epstein said heartburn drugs could interfere with a liver enzyme needed to process Plavix, neutralizing its effects.

He stressed that patients should not stop taking Plavix or heartburn drugs, particularly if they have a history of stomach problems.

"But if you're a person who's otherwise healthy taking Plavix, you might want to consider calling your doctor and asking, 'Do I need really need this' or 'Do I need it every day?' " Epstein said in an interview. "There are ways to look at this question now that we wouldn't have thought about previously."

Bristol-Myers also urged patients to talk with their doctor before taking action and questioned Medco's approach.

"While we are still reviewing the data, in general, retrospective analyses — in contrast to randomized clinical trials — are more subject to confounding factors," said spokesman Ken Dominski.

Academics at the the American Heart Association's annual meeting in New Orleans, where the data was presented, had similar concerns.

Dr. Robert Harrington of Duke University said that without a rigorous study comparing patients with similar health profiles "you cannot assume that the groups are balanced" and the results are real rather than a fluke.

For example, he said, people taking proton pump inhibitors may also have other health problems that skew their risk for heart disease.

"I would not change practice based on these data," said Harrington, who led an American College of Cardiology panel that last month said it was reasonable for doctors to prescribe these two drugs together.

All patients in the Medco study had been implanted with a stent, or a wire-mesh tube used to prop open arteries after they have been cleared of plaque. The study tracked whether they had been hospitalized for the heart and circulatory problems within a year of the stent being implanted.

In patients who had not suffered a previous heart attack, 32.5 percent patients who took Plavix and a heartburn drug experienced one of the severe events within a year of their stent surgery. Those events were seen in just 21.2 percent of patients who took only Plavix.

In patients who had suffered a previous heart attack, 39.8 percent of patients experienced the severe events within a year. In patients who did not take the heartburn drugs, only 26.2 percent did.