Do proton pump inhibitors cause heart attacks?



There has been concern for several years about commonly prescribed antacid drugs called proton pump inhibitors (PPIs) and the heart.  PPIs are used to treat gastroesophageal reflux disease (GERD), peptic ulcer disease, and other acid-related diseases.  Common drugs in the PPI class are omeprazole (Prilosec), esomeprazole (Nexium), pantoprazole (Protonix), lansoprazole (Prevacid), and dexlansoprazole (Dexilant), among others.

Specifically, there is a potential interaction between certain PPIs and clopidogrel (Plavix), where the net result is that the effectiveness of clopidogrel may be lowered by coadministration with PPIs.  Clopidogrel is an antiplatelet drug that is often given to patients who receive cardiac stents, and it happens to be metabolized to its active form by the same liver enzyme that metabolizes most PPIs.  The drugs compete for the enzyme, and this can lower the effect of clopidogrel.  Theoretically, this can lead to adverse cardiac outcomes in patients with stents.  This in vitro effect was not found clinically meaningful in a recent randomized controlled trial, however the PPI-Plavix interaction is still a controversial topic and further details are beyond the scope of this article.

I bring up the PPI/clopidogrel issue because it becomes important in understanding a new study published this month in the journal PLoS ONE.  This study used a technique called “data-mining” to extract information from years of electronic medical records (EMRs) and included about 70 thousand patients in their primary analysis.  They describe the data-mining technique in the article, which seems to boil down to assigning a mathematical function to certain defined variables (patients taking PPIs) and an outcome (heart attack) to see if the two events are associated.

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