Adults who use proton pump inhibitors such as Prevacid, Nexium and Prilosec are between 16 and 21 percent more likely to experience a heart attack than people who don’t use the commonly prescribed antacid drugs, according to a massive new study by Houston Methodist and Stanford University scientists.

An examination of 16 million clinical documents representing 2.9 million patients also showed that patients who use a different type of antacid drug called an H2 blocker have no increased heart attack risk. The findings, reported in PLOS ONE, follow a Circulation report in 2013 in which scientists showed how — at a molecular level — PPIs might cause long-term cardiovascular disease and increase a patient’s heart attack risk.

"Our earlier work identified that the PPIs can adversely affect the endothelium, the Teflon-like lining of the blood vessels," said John Cooke, M.D., Ph.D., a senior author of the PLOS ONE report. "That observation led us to hypothesize that anyone taking PPIs may be at greater risk for heart attack. Accordingly, in two large populations of patients, we asked what happened to people that were on PPIs versus other medications for the stomach."

In the present study, the researchers found a clear and significant association between exposure to PPIs and the occurrences of heart attack.

"By looking at data from people who were given PPI drugs primarily for acid reflux and had no prior history of heart disease, our data-mining pipeline signals an association with a higher rate of heart attacks," said the PLOS ONE report’s lead author, Nigam H. Shah, Nigam H. Shah, M.B.B.S., Ph.D., an assistant professor of biomedical informatics at Stanford, where the work was done. "Our results demonstrate that PPIs appear to be associated with elevated risk of heart attack in the general population, and H2 blockers show no such association." H2 Blockers are drugs such as Tagament, Pepcid and Zantac.

The estimated increase of heart attack risk with the use of PPIs ranges from 16 to 21 percent, because of uncertainty in the estimation process, Shah said.

In the future, the researchers say they hope to conduct a large, prospective, randomized trial to determine whether PPIs are harmful to a broader population of patients.

Previously, PPIs have been connected to increased instances of the bowel disease Clostridium difficile. PPIs have already linked with several other adverse events, including arrhythmias, seizures, clopidogrel resistance, osteoporotic fractures, cardiac birth defects, and decrease in magnesium levels resulting in an increased risk of leg spasms.