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Proton Pump Inhibitors Do Not Increase MI Risk

Information sourced from NEJM Journal Watch:

Proton-Pump Inhibitors Do Not Increase the Risk for Myocardial Infarction

Findings suggest that previous positive associations observed between PPIs and MI were the result of residual confounding.

Proton-pump inhibitors (PPIs) have been associated with a host of adverse effects in observational database studies. Unfortunately, information in the lay press has motivated some patients and physicians to avoid appropriate PPI use for fear of these adverse events.

To investigate the reported association of PPI use with myocardial infarction (MI), researchers evaluated data from commercial health insurance and Medicare claim databases from 2001 to 2014. Patients were followed from the first PPI or histamine-2 receptor antagonist (H2RA) prescription. The primary outcome was hospitalization for an MI. Researchers used a propensity-matching method to reduce measured confounding.

Among 5 million new users of PPIs or H2RAs identified, the 12-month weighted risk for MI was approximately 2 per 1000 and 8 per 1000 patients in commercially insured and Medicare populations, respectively. There were no differences in MI risk between PPI and H2RA use in either the commercial or Medicare groups. The findings were similar in multiple sensitivity analyses.


While this study has the limitation of using administrative databases, it also has advantages of using an active comparator (H2RAs) and controlling for measured confounding using propensity score–based methods. This analysis demonstrates that more-rigorous analysis of adverse effects reported from observational studies often shows that the initial association is the result of residual confounding. While PPIs should only be used for appropriate indications in the lowest effective dose, the alarm caused by reporting in the lay press of many associated side effects should not deter patients and physicians from using them appropriately.

David J. Bjorkman, MD, MSPH (HSA), SM (Epid.) reviewing Landi SN et al. Gastroenterology 2017 Nov 6.

Note to readers: At the time we reviewed this paper, its publisher noted that it was not in final form and that subsequent changes might be made.


Landi SN et al. No increase in risk of acute myocardial infarction in privately insured adults prescribed proton pump inhibitors vs histamine-2 receptor antagonists (2002–2014). Gastroenterology 2017 Nov 6; [e-pub].

NEJM Journal Watch is produced by NEJM Group, a division of the Massachusetts Medical Society. Copyright ©2017 Massachusetts Medical Society. All rights reserved.

The above message comes from NEJM Journal Watch, who is solely responsible for its content.

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