Proton pump inhibitors and the risk of severe adverse events - A cardiovascular bombshell?

Abstract

Proton pump inhibitors are currently one of the most prescribed pharmacological classes in developed countries, given their effectiveness and safety profile, which has until now been considered favorable. However, in recent years, several papers have been published that associate prolonged use of these drugs with a wide range of adverse effects, posing doubts about their safety. Among the adverse effects described is an increased risk of cardiovascular events. This relationship was first described in subjects after acute coronary syndrome due to the interference of proton pump inhibitors in the cytochrome P450 2C19 and the conversion of clopidogrel to its active metabolite. More recent studies have also reported this relationship with the use of antiplatelet agents that do not depend on cytochrome P450 2C19 activation. The proposed mechanism is inhibition of dimethylarginine dimethylaminohydrolase, a physiological inhibitor of asymmetric dimethylarginine, which increases plasma concentrations of the latter enzyme, leading to lower levels of nitric oxide. By reviewing in this article the relationship between the use of proton pump inhibitors and increased risk of cardiovascular and cerebrovascular events, the authors aim to alert the medical community to the potentially harmful effects of these drugs, and recommend the setting of a moratorium on their prolonged use.

Keywords: Acidente vascular cerebral; Acute coronary syndrome; Inibidores da bomba de protões; Nitric oxide; Proton pump inhibitors; Stroke; Síndrome coronária aguda; Óxido nítrico.