The results of a recent Stanford University study show a link between heartburn treatments like Prilosec and an elevated risk of heart attack.

Researchers used novel data mining techniques to scour the medical records of 19 million visits between patients and physicians at Stanford, plus more records from a private database. The found that in patients who used proton pump inhibitors like Prilosec, there was a 16- to 21 percent increase in the incidence of heart attacks.

Notably, the study revealed an increase in heart attacks among PPI users who were younger, had no prior history of heart attacks, and were otherwise healthy.

This study addressed a hypothesis put forth in an earlier study, published in the journal Circulation in 2013. Scientists then theorized that PPIs initiated a chain of events in the body that led to a lower level of nitric oxide in blood vessel tissue. Findings from the Stanford study are consistent with that theory. The newer study found that the different rates of cardiovascular risk associated with different PPIs paralleled the degree to which each of those drugs reduced levels of nitric oxide.

Earlier studies had shown a higher incidence of heart attack for PPI patients who also took the antiplatelet drug clopidogrel, a treatment for blood clots. Based on those findings, some scientists had supposed that the link between PPIs and heart attack might have something to do with the drugs’ effect on platelets. However, the new study from Stanford was able to separate the effects of clopidogrel, revealing a relationship between PPIs and heart attack that is independent of clopidogrel use.

The researchers also compared the data for PPIs to corresponding data for another class of heartburn medications called H2 inhibitors. This class includes the drugs Axid, Zantac 75, Pepcid, Tagamet, and Mylanta AR. The researchers found no link between these types of drugs and heart attack, as they did with PPIs.

The Stanford researchers noted that using the same data mining technique years ago could have revealed this correlation as early as 2000.

The current FDA-approved label for Prilosec does not mention any risk of heart attack. It does say that some Prilosec patients have reported cardiovascular symptoms of “[c]hest pain or angina, tachycardia, bradycardia, palpitations, elevated blood pressure” and “peripheral edema.”

Prilosec (also known by its generic name omeprazole) and other PPIs work by reducing the acidity in the stomach to relieve symptoms of ordinary heartburn and gastroesophageal reflux disease.

As a PPI, Prilosec is one of the most widely used drugs in the world. In the U.S. alone, more than 21 million patients were prescribed a PPI during 2009. Since then, the FDA approved an over-the-counter version of Prilosec (sold as Prilosec OTC), making it even more readily available. Annual worldwide sales of PPIs have reached $14 billion.

The Stanford researchers expressed concern that such a widely used class of drugs may not be as safe as previously thought. But they also cautioned Prilosec patients not to cease their medication without first consulting their physician. The current science shows only a correlation and does not support a causal connection, they said.