Proton-Pump Inhibitors and Death — Association or Causation?

Recent observational studies indicate associations between proton-pump inhibitors (PPIs) and numerous long-term side effects. In another such study, investigators used a large Veterans Affairs database to identify patients beginning therapy with an H2 receptor antagonist (H2RA) or a PPI and followed them for a median of 6 years.

Compared with H2RA users, PPI users were more likely to die during the observation period (hazard ratio, 1.25). Comparisons between PPI users and nonusers, and between PPI users and nonusers of either PPIs or H2RAs, yielded similarly increased risk for death with PPI use. This increased risk was also seen in patients without gastrointestinal diseases. Propensity matching on multiple comorbidities and covariates produ…