Adults who use proton pump inhibitors (PPIs) are 16% to 21% more likely to experience a heart attack than are people who do not use PPIs, according to a study published online in PLoS ONE. 

Lead author Nigam H. Shah, MBBS, PhD, and colleagues used a novel data-mining approach to examine 16 million clinical documents from 2.9 million patients. Focusing on patients given PPIs primarily for gastroesophageal reflux disease (GERD) and who had no prior history of heart disease, the researchers found a 1.16-fold increased association with myocardial infarction. 

A survival analysis in a prospective cohort found a twofold increase in association with cardiovascular mortality. Use of H2 receptor antagonists was not associated with an increased risk for myocardial infarction. 

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In 2013, Dr. Shah reported that PPIs may adversely affect vascular function by elevating levels of plasma asymmetric dimethylarginine, which has been associated with increased risk for cardiovascular disease (Circulation;128[8]:845-853). 

“This led us to use powerful ‘big-data’ approaches to try to determine whether PPIs might in fact be associated with risk in ‘all comers,'” said Nicholas J. Leeper, MD, the PLoS ONE study’s principal investigator. “Our report raises concerns that these drugs—which are available over the counter and are among the most commonly prescribed drugs in the world—may not be as safe as we previously assumed.”