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The widely used drugs known as proton pump inhibitors, or P.P.I.’s — gastric reflux preventives like Prilosec and Prevacid — may increase the risk for heart attack, according to analysis of data involving almost three million people.

Previous studies have found that P.P.I.’s are associated with poor outcomes for people with heart disease, probably because of an interaction with clopidogrel, a drug commonly prescribed after a heart attack. This new study examines the heart attack risk in otherwise healthy people.

The researchers used data-mining, a mathematical method of looking at trends in large amounts of data, to analyze the use of the drugs over time. Evidence that they were increasing the risk for heart attack was clear as early as 2000.

“This is the kind of analysis now possible because electronic medical records are widely available,” said the lead author, Nigam H. Shah, an assistant professor of medicine at Stanford. “It’s a benefit of the electronic records system that people are always talking about.”

There was no association of heart attack with another class of drugs used to treat gastric reflux, H2 blockers like Zantac, Tagamet and Pepcid. The researchers suggest that P.P.I.’s promote inflammation and clots by interfering with the actions of protective enzymes.

A significant limitation of the study, in PLOS One, is that P.P.I. usage may be a marker of a sicker patient population, more subject to heart disease in any case.