PPIs are some of the most commonly prescribed drugs in the world but are also available for purchase over the counter.
A different type of antacid drug known as an H2 blocker was not associated with an increase in heart attack risk, however.
Proton pump inhibitors (PPIs) are frequently prescribed to treat a variety of conditions, including gastroesophageal reflux disease (GERD) and Helicobacter pylori infection. Names for these drugs - lansoprazole and omeprazole, for example - always feature the suffix "-prazole."
In 2009, they were the third most taken type of drug in the US, and the Food and Drug Administration (FDA) estimates 1 in 14 Americans have used them. Over time, however, experts have begun to question the safety of the drug.
Experts initially believed that use of PPIs was only risky for patients with coronary artery disease who were also using the antiplatelet drug clopidogrel, considering the risk to be caused by a drug-drug interaction. More recent studies, however, have indicated that the risk may extend further.
"Our earlier work identified that the PPIs can adversely affect the endothelium, the Teflon-like lining of the blood vessels," reports senior author Dr. John Cooke. "That observation led us to hypothesize that anyone taking PPIs may be at greater risk for heart attack."
For the study, published in PLOS ONE, researchers from Houston Methodist and Stanford University compared heart attack risk for patients using PPIs with patients using other forms of stomach medication.
Data were collected from 16 million clinical documents for around 2.9 million patients. These documents were obtained from two databases; the Stanford Translational Research Integrated Database Environment (STRIDE) and Practice Fusion, an electronic medical records company.
PPIs associated with increased heart attack risk, unlike H2 blockers
The researchers extracted information from these databases for any patients reported to have been prescribed PPIs or other similar drugs, such as H2 blockers, and then looked to see if these patients had also experienced a major cardiovascular event such as a heart attack.
H2 blockers such as cimetidine and ranitidine are another form of antacid. Unlike PPIs, they have yet to be associated with an increased risk of heart attack or cardiovascular disease.
"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," says lead author Nigam H. Shah, an assistant professor of biomedical informatics at Stanford, adding:
"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."
Due to uncertainty with the estimation process, the researchers report that the increase in risk of heart attack sits between 16-21%.
As the observational data used in the study is vulnerable to confounding in multiple ways, the researchers hope to conduct a more reliable large, prospective, randomized trial to confirm whether PPIs are harmful to a wider population of patients.
"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," concludes principal investigator Dr. Nicholas J. Leeper, a vascular medicine specialist at Stanford.