Long-term acid inhibition: benefits and harms.

Proton pump inhibitors (PPIs) are the drugs of choice in the therapy of acid-related disorders. PPIs are as a class remarkably safe. Serious adverse events such as acute interstitial nephritis are extremely rare. Some reports in recent years have placed some concern on the long-term use of PPIs. Long-term therapy with PPIs can cause hypochlorhydria, hypergastrinemia and has interactions on hepatic cytochrome P450 enzymes which might increase the risk of infectious complications, nutritional deficiencies and drug-drug interactions. The vast majority of data came from retrospective case-control or cohort studies which are prone to confounders. At the moment we cannot conclude that long-term PPI use causes anemia, osteoporosis and bone fractures, increases the risk for pulmonary or enteric infections, has an effect on GUT mucosa, polyp or tumor formation, or that PPI use increases the risk of cardiovascular events in patients on PPIs and clopidogrel. We need prospective randomized trials to be able to definitely answer the questions raised in epidemiologic studies. Maintenance therapy with PPIs should be started only if strict indications for that therapy are fulfilled.