Do the Benefits of PPIs Outweigh Risks?


Although proton pump inhibitors are widely used, they are not without risks.

Proton pump inhibitors (PPIs) have been among the most prescribed medications for decades, and they have also been available OTC since 2003.

Although PPIs are widely used, they are not without risks. According to the American College of Gastroenterology's guidelines for gastroesophageal reflux disease (GERD), potential risks associated with PPIs include:

  • Osteoporosis due to reduction in gastric acid and decreased release of ionized calcium from calcium salts and protein-bound calcium.
  • Clostridium difficile infection due to increased gastric pH levels and growth of gut microflora.
  • Community-acquired pneumonia with short-term usage.

In 2009, the FDA issued warnings about the potential for adverse cardiovascular events among clopidogrel users taking PPIs.

One year later, it warned about the potential for wrist, hip, and spine fractures among PPI users.

In June 2015, PLOS One published the results of a large data-mining study that linked PPIs to an elevated risk of heart attack. These results have led many patients to consider discontinuing PPI therapy.

In the eyes of many health care professionals, PPIs are overprescribed. While not every patient who receives a PPI is using it for the correct indication, the American Gastroenterological Association (AGA) stated that this study shouldn’t spur changes in practice.

The AGA recommends reminding patients that all treatments have risks and benefits and that PPIs should be used at the lowest effective dose. The study showed a modest absolute increased risk in that only 1 of 4000 patients treated with PPIs would have a heart attack.

In 2011, noted gastroenterologist Colin W. Howden, MD, AGAF, discussed the risks of long-term PPI therapy on the AGA website. Dr. Howden acknowledged that he discontinued PPI therapy far more often than he initiated it because many of his patients were started on a PPI inappropriately.

Nevertheless, he felt “strongly that the benefits of PPI therapy for appropriate clinical indications greatly outweigh any risks for most patients.” Based on the AGA's heart attack risk statement, patients should continue therapy until they receive individual advice from their prescriber.

To paraphrase Dr. Howden, when a PPI is genuinely indicated, it’s best to “keep calm and carry on.”


1. Katz P, Gerson L, et al. Guidelines for the Diagnosis and Management of Gastroesophageal Reflux Disease. Am J Gastroenterol. 2013; Vol 108:308-328.

2. Some heartburn drugs may boost risk of heart attack, study finds. Stanford Medicine website. Accessed July 2015.

3. Shah NH, LePendu P, Bauer-Mehren A, Ghebremariam YT, Iyer SV, et al. (2015) Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population. PLOS One 10(6): e0124653.

4. Interpretation of Study on PPI-Heart Attack Risk. American Gastroenterological Association website. Accessed July 2015.

5. Long-Term PPI Therapy Risks: “Keep Calm and Carry On”. American Gastroenterological Association website. Accessed July 2015.

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