PPI use associated with all-cause and cause-specific mortality


Background: PPI use has previously been associated with an increased risk of acute kidney injury, Clostridium difficile infection, osteoporosis, dementia, and all-cause mortality. An estimation of the level of mortality risk, as well as cause-specific mortality risk, may better inform decisions about prescribing PPIs.

Dr. Derek S. Kruse is a hospitalist at Vanderbilt University Medical Center, Nashville, Tenn.

Dr. Derek S. Kruse

Study design: Longitudinal observational cohort.

Setting: Department of Veterans Affairs.

Synopsis: Using a cohort of veterans newly prescribed acid suppression therapy in 2002-2004, 157,625 new PPI users were compared with 56,842 new H2 receptor–blocker users. Over the following 10 years, a specific cause of death was determined using national death index data. In that period, 37.3% of patients died, with PPI use associated with 45.2 excess deaths per 1,000 patients (95% confidence interval, 28.2-61.4). There were significant associations with the following specific causes of death: circulatory system diseases (17.5 excess deaths per 1,000 patients, 95% CI, 5.5-28.8), neoplasms (12.9; 95% CI, 1.2-24.3), genitourinary system diseases including chronic kidney disease (6.3; 95% CI, 1.6-7.0), and infectious/parasitic diseases (4.2; 95% CI, 3.2-9.2).

Limitations include the observational study design and potential for confounding variables not accounted for by the researchers. There is also a question of broader applicability given the VA patient population. Nevertheless, this study adds to growing evidence regarding risks associated with PPI use. Clinicians should consider prescribing PPIs only for indications and durations where it is known to offer benefit in order minimize risk of adverse events.

Bottom line: PPI use is associated with an excess risk of death, particularly death caused by cardiovascular disease, malignancy, genitourinary diseases, and infection.

CITATION: Xie Y et al. Estimates of all-cause mortality and cause specific mortality associated with proton pump inhibitors among US veterans: Cohort study. BMJ. 2019 May 29;365:l1580.

Dr. Kruse is a hospitalist at Vanderbilt University Medical Center, Nashville, Tenn.

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