[What is the REAL long-term risk of proton pump inhibitors?]

Proton pump inhibitors (PPIs) are among the most prescribed drugs in the world. While their efficacy in acute management is indisputable, it has long been suggested that PPI therapy is safe in the long term. In recent years, there has been growing and justified concern about the long-term risks of PPIs. The majority of reported side effects are based on observational studies with a low level of evidence. Concerning digestive risks, PPIs seem to increase the risk of Salmonella and Campylobacter infections. However, the link between PPIs and Clostridium difficile infection is not established. Long-term PPIs may be responsible for an increased risk of gastric cancer according to several recent studies. With regard to extra-digestive risks, PPIs are associated with a moderate increase in the risk of chronic renal failure via an interstitial nephritis mechanism. PPIs also provide martial deficiency and may be associated with vitamin B12 and magnesium deficiency in some patients. Other adverse reactions have been suggested without any causal relationship being established (i.e., dementia or bone fractures, cardiovascular risk). In this review we will discuss the different long-term adverse effects of PPIs and their level of evidence.