More evidence & warnings on PPI use

Medicines

By Mardi Chapman

6 Jun 2019

Long known to be associated with the risk of serious adverse events, proton pump inhibitors (PPIs) have now been shown to increase the risk of all cause mortality, and specifically deaths due to cardiovascular disease and chronic kidney disease.

The findings reinforce messages to consumers and clinicians that the drugs should only be used when medically indicated and for the minimum duration necessary.

The longitudinal cohort study of US veterans followed 157,625 new users of PPIs and 56,842 new users of H2 blockers for a median duration of 10 years.

Veterans were mostly white males with an average age of 65 years.

The study found there were 45.20 excess deaths per 1,000 PPI users.

Causes of death that showed significant excess mortality were circulatory system diseases, neoplasms, genitourinary system diseases and infectious or parasitic diseases (17.47, 12.94, 6.25, 4.20 attributable deaths per 1,000 PPI users respectively).

The study found a graded relation between duration of drug exposure and risks of death due to circulatory system diseases, neoplasms and genitourinary system diseases but not due to infectious or parasitic diseases.

When causes of deaths were mapped to known adverse events from PPIs, sub causes of excess deaths were observed from cardiovascular disease and chronic kidney disease (15.48 and 4.19 attributable deaths per 1,000 PPI users respectively).

The relationships between PPIs and cardiovascular or chronic kidney disease were not modified by the presence of related comorbidities at baseline.

The study found PPI use was not associated with increased mortality due to digestive system diseases but in patients without a documented indication for acid suppression drugs, PPI use was associated with risk of death from upper gastrointestinal cancer.

“Our findings suggest that although PPI use might be associated with many serious adverse events, excess mortality was only mapped to a few specific causes including cardiovascular disease, chronic kidney disease, and upper gastrointestinal cancer.”

“Notably, excess burden was present in those without underlying documented indications for PPI use, that is, patients who may not benefit from PPI exposure.”

The researchers said their results should not preclude prescription and use of PPIs where medically indicated.

“…nevertheless, the findings emphasize the need to promote awareness of potential adverse events of long term PPI use, for better pharmacovigilance, and the need to limit prescription of PPIs to patients where the benefits outweigh potential risks.”

They said deprescribing strategies to reduce unnecessary or un-indicated use of PPIs were warranted. Over-the-counter use of PPIs should generally not exceed 14 days.

 

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