Proton pump inhibitors (PPIs) are used by many millions of people every day to treat heartburn and gastroesophageal reflux disease (GERD). However, according to a study in PLoS One, they could increase the risk of a heart attack by up to a fifth.
There have been concerns about clinical outcomes in patients who use both clopidogrel and PPIs and who have had an acute coronary syndrome episode. To find out more about this connection, and about the risk in people who are otherwise healthy, researchers from Houston Methodist Research Institute and Stanford University looked at more than 16 million documents from the anonymized medical records of 2.9 million people in STRIDE (Stanford Translational Research Integrated Database Environment) and in the database of the electronic medical records company Practice Fusion. This research follows on from preclinical studies published in 2013 in Circulation.
“Our earlier work identified that the PPIs can adversely affect the endothelium, the Teflon-like lining of the blood vessels,” says John Cooke of Houston Methodist Research Institute. “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.”
Mining this data showed a 16-21% increased risk of heart attack (myocardial infarction; MI) in people with GERD taking PPIs, compared with those who don’t, irrespective of clopidogrel use. There was no link with H2 blockers.
“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 Nigam H Shah, Stanford University. “Our results demonstrate that PPIs appear to be associated with elevated risk of heart attack in the general population.”
In 2009, PPIs were the third-most taken type of drug in the US, available both on prescription and over-the-counter, and are believed to account for $13 billion in annual global sales. They are prescribed for a wide range of disorders, including GERD, ulcers, Zollinger-Ellison syndrome, and Barrett’s esophagus. As a next step, researchers hope to conduct a large, prospective, randomized trial to determine whether PPIs are harmful to a broader population of patients.