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. 2019 May 29:365:l1580.
doi: 10.1136/bmj.l1580.

Estimates of all cause mortality and cause specific mortality associated with proton pump inhibitors among US veterans: cohort study

Yan Xie  1   2 , Benjamin Bowe  1   3 , Yan Yan  1   4 , Hong Xian  1   3 , Tingting Li  1   5 , Ziyad Al-Aly  6   2   5   7   8
Affiliations

Estimates of all cause mortality and cause specific mortality associated with proton pump inhibitors among US veterans: cohort study

Yan Xie et al. BMJ. .

Abstract

Objective: To estimate all cause mortality and cause specific mortality among patients taking proton pump inhibitors (PPIs).

Design: Longitudinal observational cohort study.

Setting: US Department of Veterans Affairs.

Participants: New users of PPIs (n=157 625) or H2 blockers (n=56 842).

Main outcome measures: All cause mortality and cause specific mortality associated with taking PPIs (values reported as number of attributable deaths per 1000 patients taking PPIs).

Results: There were 45.20 excess deaths (95% confidence interval 28.20 to 61.40) per 1000 patients taking PPIs. Circulatory system diseases (number of attributable deaths per 1000 patients taking PPIs 17.47, 95% confidence interval 5.47 to 28.80), neoplasms (12.94, 1.24 to 24.28), infectious and parasitic diseases (4.20, 1.57 to 7.02), and genitourinary system diseases (6.25, 3.22 to 9.24) were associated with taking PPIs. There was a graded relation between cumulative duration of PPI exposure and the risk of all cause mortality and death due to circulatory system diseases, neoplasms, and genitourinary system diseases. Analyses of subcauses of death suggested that taking PPIs was associated with an excess mortality due to cardiovascular disease (15.48, 5.02 to 25.19) and chronic kidney disease (4.19, 1.56 to 6.58). Among patients without documented indication for acid suppression drugs (n=116 377), taking PPIs was associated with an excess mortality due to cardiovascular disease (22.91, 11.89 to 33.57), chronic kidney disease (4.74, 1.53 to 8.05), and upper gastrointestinal cancer (3.12, 0.91 to 5.44). Formal interaction analyses suggested that the risk of death due to these subcauses was not modified by a history of cardiovascular disease, chronic kidney disease, or upper gastrointestinal cancer. Taking PPIs was not associated with an excess burden of transportation related mortality and death due to peptic ulcer disease (as negative outcome controls).

Conclusions: Taking PPIs is associated with a small excess of cause specific mortality including death due to cardiovascular disease, chronic kidney disease, and upper gastrointestinal cancer. The burden was also observed in patients without an indication for PPI use. Heightened vigilance in the use of PPI may be warranted.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Figures

Fig 1
Fig 1
Flowchart for cohort building
Fig 2
Fig 2
Flowchart for analytic approach
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