Proton pump inhibitors as part of comedication with antithrombotic drugs: are their indications justified?

The administration of proton pump inhibitors (PPIs) along with antithrombotic therapy indicated to reduce gastrointestinal bleeding is common practice. Evidence of reduced bleeding risk with this strategy is only available at the level of observational studies, with a reduction by approximately one-third being significant. However, with a relatively low rate of gastrointestinal bleeding, the absolute risk reduction is small, somewhere near 0.3 %. The observed value of NNT (number needed to treat) is around 250, i.e. for every 250 patients treated with PPIs, one bleeding episode (typically not a critical one) is prevented. On the other hand, there has been an increasing number of papers reporting a higher rate of cardiovascular events, renal failure, and neural involvement in the case of treatment with PPIs. In the population with a high cardiovascular risk, i.e. a typical population in which PPIs are added to antithrombotic therapy, the risk is significant. The value of NNH (number needed to harm) is around 50. There may be multiple reasons for increased cardiovascular morbidity and mortality, ranging from gastroesophageal involvement itself to comprehensive action of PPIs on numerous transporters or enzymes to negative action of PPIs related to drug-drug interactions.

Keywords: proton pump inhibitors, H₂ receptor blockers, adverse effects, cardiovascular mortality, myocardial infarction, renal failure.