Proton pump inhibitors, adverse events and increased risk of mortality.

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.