Proton pump inhibitors, adverse events and increased risk of mortality

ABSTRACT

Introduction: Proton pump inhibitors (PPIs) are among the most commonly prescribed drugs worldwide. However, concerns are growing about the serious adverse events and mortality linked to their long-term use.

Areas covered: The authors review the main approved clinical indications and adverse events associated with PPIs, including, among others, pneumonia, Clostridium difficile infection, cardiovascular diseases, bone fractures, kidney diseases, and several nutrient deficiencies. Recent studies have reported that patients taking PPIs displayed increased mortality, linked to cardiovascular diseases, gastrointestinal malignancies, and chronic kidney diseases.

Expert opinion: PPIs represent an important advance in the medical treatment of acid-related diseases. PPIs have contributed to profound reductions in hospitalizations and mortality due to upper GI complications. However, concern is growing about the wide range of potentially serious adverse events and mortality linked to chronic PPI use. Nevertheless, the level of evidence on adverse events is low; it is based on observational studies, and most findings have not been confirmed in the limited number of clinical trials available. PPI overuse and off-label prescriptions must be eradicated, but long-term PPI use for clear indications must continue, until we have stronger evidence to support claims of serious adverse events and mortality.

KEYWORDS:

• Proton pump inhibitors
• complications
• safety
• mortality

Article highlights

• PPIs are very effective in the treatment of acid-related diseases, but they are being overused for non-approved clinical indications.

• A number of serious adverse events have been associated with chronic long-term PPI use.

• The most frequently reported PPI-related adverse events include pneumonia, Clostridium difficile and other enteric infections, liver encephalopathy, cardiovascular diseases, bone fractures, and several nutrient deficiencies.

• Recently, several studies reported an overall increase in mortality among patients taking PPIs, which was linked to cardiovascular diseases, gastrointestinal malignancies, and chronic kidney diseases.

• Unlike the beneficial effects of PPIs, the level of evidence is low for PPI-related adverse events; most evidence is based on observational studies; often the results are contradictory; and most results have not been confirmed in clinical trials.

• PPI overuse and prescriptions for non-approved indications must be eradicated, but long-term PPI use in patients with a clear indication must be maintained until we have stronger evidence to support the risk of potentially serious adverse events and increased mortality.

Acknowledgments

The authors acknowledge revision and edits of the manuscript by San Francisco Edit. This work was possible thanks to funds from Fondos Feder and DGA group B25_17R.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by the Instituto de Investigación Sanitaria Aragón and Centro de Investigación Biomédica en red en enfermedades hepáticas y digestivas (CIBERehd).