Association Between Proton-Pump Inhibitors and Mortality

In observational studies, proton-pump inhibitors (PPIs) have been associated with various clinical disorders, but many of those associations are controversial because bias and confounding were possible. In this longitudinal observational study of U.S. veterans (mean age, 65), researchers estimated excess risks for all-cause and cause-specific death conferred by PPIs (with histamine [H₂]-blockers as the active comparator).

Participants were 158,000 new users of PPIs and 57,000 new users of H₂-blockers. Complex statistical analysis was employed to minimize confounding. During a median follow-up of 10 years, about 45.5 excess deaths occurred per 1000 PPI users (18, 13, 6, and 4 excess deaths attributed to circulatory system diseases, neoplasms,…