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BMJ Open. 2017 Jul 4;7(6):e015735. doi: 10.1136/bmjopen-2016-015735.

Risk of death among users of Proton Pump Inhibitors: a longitudinal observational cohort study of United States veterans.

Xie Y1, Bowe B1, Li T1,2, Xian H1,3, Yan Y1,4, Al-Aly Z1,2,5,6.

Author information

1
Clinical Epidemiology Center, Research and Education Service, VA Saint Louis Health Care System, Saint Louis, Missouri, USA.
2
Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA.
3
Department of Biostatistics, College for Public Health and Social Justice, Saint Louis University, Saint Louis, Missouri, USA.
4
Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, Saint Louis, Missouri, USA.
5
Renal Section, Medicine Service, VA Saint Louis Health Care System, Saint Louis, Missouri, USA.
6
Institute for Public Health, Washington University in Saint Louis, Saint Louis, Missouri, USA.

Abstract

OBJECTIVE:

Proton pump inhibitors (PPIs) are widely used, and their use is associated with increased risk of adverse events. However, whether PPI use is associated with excess risk of death is unknown. We aimed to examine the association between PPI use and risk of all-cause mortality.

DESIGN:

Longitudinal observational cohort study.

SETTING:

US Department of Veterans Affairs.

PARTICIPANTS:

Primary cohort of new users of PPI or histamine H2 receptor antagonists (H2 blockers) (n=349 312); additional cohorts included PPI versus no PPI (n=3 288 092) and PPI versus no PPI and no H2 blockers (n=2 887 030).

MAIN OUTCOME MEASURES:

Risk of death.

RESULTS:

Over a median follow-up of 5.71 years (IQR 5.11-6.37), PPI use was associated with increased risk of death compared with H2 blockers use (HR 1.25, CI 1.23 to 1.28). Risk of death associated with PPI use was higher in analyses adjusted for high-dimensional propensity score (HR 1.16, CI 1.13 to 1.18), in two-stage residual inclusion estimation (HR 1.21, CI 1.16 to 1.26) and in 1:1 time-dependent propensity score-matched cohort (HR 1.34, CI 1.29 to 1.39). The risk of death was increased when considering PPI use versus no PPI (HR 1.15, CI 1.14 to 1.15), and PPI use versus no PPI and no H2 blockers (HR 1.23, CI 1.22 to 1.24). Risk of death associated with PPI use was increased among participants without gastrointestinal conditions: PPI versus H2 blockers (HR 1.24, CI 1.21 to 1.27), PPI use versus no PPI (HR 1.19, CI 1.18 to 1.20) and PPI use versus no PPI and no H2 blockers (HR 1.22, CI 1.21 to 1.23). Among new PPI users, there was a graded association between the duration of exposure and the risk of death.

CONCLUSIONS:

The results suggest excess risk of death among PPI users; risk is also increased among those without gastrointestinal conditions and with prolonged duration of use. Limiting PPI use and duration to instances where it is medically indicated may be warranted.

KEYWORDS:

Adverse events; CLINICAL PHARMACOLOGY; EPIDEMIOLOGY; Gastroduodenal disease; Health & safety; PUBLIC HEALTH

PMID:
28676480
PMCID:
PMC5642790
DOI:
10.1136/bmjopen-2016-015735
[Indexed for MEDLINE]
Free PMC Article

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