Popular heartburn drugs such as Nexium don't keep the blood thinner Plavix from working effectively, according to a new study, and don't put patients who take the pills at a higher risk for heart attack.

The study, to be published in the British medical journal The Lancet on Tuesday, contrasts earlier research showing patients who combined a heartburn pill like Nexium or Prilosec with Plavix have a 50% higher risk of a heart attack, compared with people taking Plavix alone.

Plavix, co-marketed by Sanofi-Aventis SA (SNY) and Bristol-Myers Squibb Co. (BMY), is the world's second most commonly prescribed drug, with worldwide sales of about $9 billion. The drug is commonly prescribed to patients with artery-opening stents or those who have had a heart attack or stroke to prevent their blood from clotting and causing another heart event.

About half of the patients taking Plavix also take Nexium, Prilosec or a similar drugs that prevent stomach bleeding and ulcers, frequent side effects with Plavix. Nexium and Prilosec belong to a class of drugs called proton-pumps inhibitors, or PPIs.

The Lancet study compared the rate of strokes and heart attacks in more than 2,000 patients who took Plavix and a PPI with those who took Plavix alone, and found the PPIs didn't interfere with Plavix. The authors of the study say the research shows patients shouldn't avoid taking popular heartburn drugs along with Plavix.

Still, the study notes, a thorough clinical trial is necessary to definitively understand how PPIs may affect Plavix.

In May, a group of cardiologists warned doctors to limit the use of PPIs with Plavix after a nearly 17,000-person study by Medco Health Solutions Inc. (MHS) and the Indiana University School of Medicine showed the heartburn pills interfered with Plavix's ability to stop blood clots.

Earlier this year, the U.S. Food and Drug Administration asked Plavix marketers Bristol-Myers and Sanofi to update the drug's label to warn of risks with the drug when used in combinations with PPIs.

Although it's unclear exactly why The Lancet study comes to a different conclusion than the Medco review, it may have to do with the overall health of the patients studied, said Dr. Robert Epstein, an author of the Medco study. Epstein said The Lancet study involved healthier patients who weren't in a "real-world setting."

The Lancet study relied on data from two clinical trials sponsored by Eli Lilly & Co. (LLY) and Daiichi Sankyo Co. (4568.TO), makers of a competitor to Plavix, where patients who were considered too unhealthy to study were excluded. The Medco study reviewed data from 16,690 patients over a year who needed cardiac intervention such as a stent.

An example of the difference in patients studied involves the percentage of cardiovascular events such as a heart attack or stoke in each of the populations. About 12% of patients reviewed in The Lancet study had a heart attack, stroke or other cardiovascular event, compared with 21% in the Medco review, suggesting The Lancet study involved healthier patients. Neither study design is considered as powerful as a clinical trial, where patients are enrolled specifically to answer a specific question - in this case, whether PPIs interfere with Plavix.

The Lancet review also found that PPIs didn't interfere with Prasugrel's ability to stop blood from clotting. Prasugrel, co-marketed by Daichii and Eli Lilly, was approved by the FDA earlier this year as a competitor to Plavix.

-By Jared A. Favole, Dow Jones Newswires; 202-862-9207; jared.favole@ dowjones.com