Higher Risk of Heart Attack Linked to Popular Heartburn Drugs

A common type of heartburn drug taken by more than 100 million people annually is linked to a higher risk of heart attacks, new research says.

According to a large new study by Houston Methodist and Stanford University scientists, adult users of proton pump inhibitor medications (PPIs) have a 16 to 21 percent higher likelihood of experiencing a heart attack than people who don’t use the common antacid drugs.

“Our earlier work identified that the PPIs can adversely affect the endothelium, the Teflon-like lining of the blood vessels,” said senior author John Cooke, M.D., Ph.D. “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.”

Physicians prescribe PPIs for treatment of a wide range of disorders, including infection by the ulcer-causing bacterium Helicobacter pylori, gastro-esophageal reflux disease (GERD), Zollinger-Ellison syndrome, and Barrett’s esophagus.

Also available for purchase over the counter in many countries, inclusing the U.S., PPIs come in a range of slightly altered chemical forms, always ending with the suffix “-prazole,” for example, omeprazole or lansoprazole.

Brandname examples of PPIs are Prilosec, Nexium, and PrevAcid.

A different type of antacid drug, H2 blockers, are not believed to be associated with increased risk of heart attack or cardiovascular disease. Examples of the drug are cimetidine and ranitidine, brandnames of H2 blockers include Zantac and Tagamet.

The findings, reported in a PLOS ONE paper, echo a 2013 report in which scientists showed how PPIs may cause long-term cardiovascular disease at a molecular level and increase a patient’s heart attack risk.

Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population
Nigam H. Shah, Paea LePendu, Anna Bauer-Mehren, Yohannes T. Ghebremariam, Srinivasan V. Iyer, Jake Marcus, Kevin T. Nead, John P. Cooke, Nicholas J. Leeper
PLOS ONE 10 Jun 2015 10.1371/journal.pone.0124653

Abstract:

“Background and Aims

Proton pump inhibitors (PPIs) have been associated with adverse clinical outcomes amongst clopidogrel users after an acute coronary syndrome. Recent pre-clinical results suggest that this risk might extend to subjects without any prior history of cardiovascular disease. We explore this potential risk in the general population via data-mining approaches.

Methods

Using a novel approach for mining clinical data for pharmacovigilance, we queried over 16 million clinical documents on 2.9 million individuals to examine whether PPI usage was associated with cardiovascular risk in the general population.

Results

In multiple data sources, we found gastroesophageal reflux disease (GERD) patients exposed to PPIs to have a 1.16 fold increased association (95% CI 1.09–1.24) with myocardial infarction (MI). Survival analysis in a prospective cohort found a two-fold (HR = 2.00; 95% CI 1.07–3.78; P = 0.031) increase in association with cardiovascular mortality. We found that this association exists regardless of clopidogrel use. We also found that H2 blockers, an alternate treatment for GERD, were not associated with increased cardiovascular risk; had they been in place, such pharmacovigilance algorithms could have flagged this risk as early as the year 2000.

Conclusions

Consistent with our pre-clinical findings that PPIs may adversely impact vascular function, our data-mining study supports the association of PPI exposure with risk for MI in the general population. These data provide an example of how a combination of experimental studies and data-mining approaches can be applied to prioritize drug safety signals for further investigation.”

Illustration: Spooky Pooka, Wellcome Images