Proton pump inhibitors – do we know them well and are they really that safe? – part 1

Proton pump inhibitors (PPIs) are one of the most commonly used drug groups. More than 10% of patients being chronically treated in the adult population. Often patients with a high risk of vascular or renal impairment. In addition to the unquestionable effect in the treatment and in the prophylaxis of gastroduodenal diseases, PPIs have been promoted in combination with antithrombotic therapy in order to reduce bleeding in the gastrointestinal tract. In both of these indications, this is a chronic treatment, often for several years. Drug regulatory agencies (EMAs or FDA) warn against chronic PPIs use, warning of a number of serious side effects. However, chronic administration of PPIs is a common practice. It is therefore time to evaluate the benefit and risk of this important drug group. First of all, it should be noted that PPIs operate not only at the level of the classical gastric proton pump (H+/K+ ATPase), but also block the activity of the sister vacuolar proton pump (V-H+-ATPase) in a number of other organs or organelles, namely lysosomes of all somatic cells. Similarly, PPIs block the activity of a number of transporters and metabolic enzymes. Action at this level is likely to surprise the gastroenterologist. There is no doubt about the benefits of PPIs in the indication of treatment and prevention of ulcerative or reflux disease. However, what are the evidence to reduce the risk of gastriontestinal bleeding in antithrombotic treatment? In this area we have data at the level of observational studies, the decrease in the risk of bleeding by about a third is significant. However, with a relatively low incidence of bleeding in the gastrointestinal tract, the absolute decrease in risk is small, hovering at 0.3%. The observed number need to treat is around 250, i.e. for every 250 PPIs treated, we will prevent one bleeding (usually not critical). On the other hand, there are increasingly work that finds a higher incidence of cardiovascular events, renal failure, bronchial asthma and nervous disabilities in chronic PPIs treatment. In a population at high cardiovascular risk, i.e. in a typical population where we add antithrombotic treatment to PPIs, the risk is significant. The number need to harm value is around 50. Thus, in the chronic use of PPIs, the risk outweighs the benefit.