Patients who take proton pump inhibitors (PPIs) may be at an increased risk for myocardial infarction (MI) and other cardiovascular outcomes, according to a data mining analysis.

However, there was no association between the use of H2 blockers and MI or cardiovascular risk. H2 blockers are alternatives to PPIs in treating gastroesophageal reflux disease.

“The current study suggests that the risk of PPIs may extend beyond previously studied high risk individuals,” wrote lead researcher Nigam H. Shah, MBBS, PhD, of the Stanford Center for Biomedical Informatics Research in Stanford, California, and colleagues. They published their findings online June 10 in PLOS One.

The researchers found that patients who received PPIs had a 1.16 fold increased association with cardiovascular risk compared with those who did not receive the drugs. They also conducted a prospective cohort survival analysis that found a doubling in risk for cardiovascular mortality associated with PPIs.

Shah et al mentioned the risk of MI is independent of clopidogrel use or age-related risks and is seen in the general population, not just in high-risk groups such as the elderly or patients with acute coronary syndrome.

They cited data that showed there are an estimated 113 million PPI prescriptions each year, and the drugs account for more than $13 billion in worldwide sales. In 2009, approximately 21 million people in the U.S. received a PPI prescription.

To evaluate the association between PPIs and cardiovascular risk, they examined a primary source from Stanford and a secondary source from Practice Fusion, Inc., which provided a free, web-based EHR system for clinicians. They also used a prospective source for the survival analysis.

In all, they searched more than 16 million clinical documents and collected data on 2.9 million patients.

The researchers evaluated the following PPIs: omeprazole, lansoprazole, pantoprazole, esomeprazole, rabeprazole and dexlansoprazole. They also evaluated H2 blockers, including cimetidine, famotidine, nizatidine and ranitidine.

They found that all PPIs were associated with increased cardiovascular risk in the general population, including young patients and patients who did not take antiplatelets. They wrote that the results suggested PPIs “may promote risk via an unknown mechanism that does not directly involve platelet aggregation.”

They cited a few potential study limitations. For instance, because they evaluated observational data, they said PPI usage might indicate patients are sicker than the general population and the findings may not be generalizable to other patients. They also did not examine over-the-counter PPIs and could not determine the dosage of PPIs that patients received.

“We recognize that these findings are hypothesis generating, and a prospective randomized study in the general population (inclusive of both lean and obese individuals) is required before changing clinical practice,” the researchers wrote. “However, the number of subjects needed to detect harm among PPI users for MI is considerable, projected to be about 4,000.”