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The risks of PPI therapy

Abstract

PPIs have become one of the most commonly used medications worldwide, as they are the treatment of choice for several acid-related gastrointestinal disorders. However, concerns have been raised about PPI therapy, including the risk of pneumonia, bone fractures and enteric infections, and a possible interaction with clopidogrel that could increase the risk of cardiovascular events. Observational studies have shown very modest associations between PPI therapy and these risks, although the association between PPI treatment and the risk of enteric infections seems to be stronger than the association with other risk factors. However, given the inherent limitations of observational studies, these associations could be attributable to bias and/or confounding factors. In addition, evidence from randomized, controlled trials does not support a clinically significant effect of PPI therapy on the risk of cardiovascular events in patients taking clopidogrel or the risk of pneumonia. Nevertheless, it is impossible to exclude the possibility that some of these associations might be causal or indeed that PPI therapy has an as yet unknown long-term adverse effect. As with any therapy, therefore, it is advisable to prescribe PPIs only to patients for whom these drugs have been proven beneficial.

Key Points

  • PPI therapy is associated with a risk of pneumonia, bone fracture and infective diarrhea; in patients taking clopidogrel, PPI therapy is associated with an increased risk of cardiovascular events

  • Many, if not all, of these associations are very modest, and, given the nature of observational studies, are probably attributable to confounding factors

  • The findings of randomized, controlled trials do not support a clinically important role of PPI therapy in reducing the effects of clopidogrel or in causing pneumonia

  • Although the possibility of adverse events attributable to PPI therapy cannot be excluded, it is important that PPIs are only given to patients who might benefit from them

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Figure 1: The duration of acid suppression intake is associated with the risk of pneumonia.18
Figure 2: An observational study has compared comorbidities in patients who were prescribed PPI therapy with those not given these drugs while evaluating the risk of pneumonia.16
Figure 3: An observational study has compared comorbidities in patients prescribed PPI therapy with the comorbidities of those not given these drugs while evaluating the risk of interaction with clopidogrel.79

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Both authors contributed equally to all aspects of this article.

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Correspondence to Paul Moayyedi.

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P. Moayyedi has acted as a consultant for AstraZeneca, Axcan Pharma and Johnson & Johnson, and has received a research grant and speaking honoraria from Abbott, AstraZeneca, Johnson & Johnson and Nycomed. His chair is partially funded by an unrestricted donation given to McMaster University by AstraZeneca. G. I. Leontiadis has acted as a consultant for AstraZeneca and Axcan Pharma, and has received a research grant from AstraZeneca and speaking honoraria from AstraZeneca, Sanofi-Aventis and GlaxoSmithKline.

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Moayyedi, P., Leontiadis, G. The risks of PPI therapy. Nat Rev Gastroenterol Hepatol 9, 132–139 (2012). https://doi.org/10.1038/nrgastro.2011.272

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