Proton pump inhibitor (PPI) use is associated with excess risk of death, according to data published in the BMJ Open. The risk of death is increased among those without gastrointestinal conditions and with prolonged use.
Yan Xie, Clinical Epidemiology Center, VA St Louis Health Care System, St Louis, Missouri, and colleagues conducted a longitudinal observational cohort study to determine the association between PPI use and risk of all-cause mortality in a cohort of new users of a PPI or histamine H2 receptor agonists from the US Department of Veteran Affairs (n=349,312). The study included an additional cohort of PPI use vs no PPI use (n=3,288,092) and a cohort of PPI use vs no PPI and no H2 blockers (n=2,887,030).
The results showed that PPI use was linked to increased mortality risk compared with H2 blocker use (hazard ratio [HR], 1.25) after a median follow-up period of 5.71 years.
Mortality risk associated with PPI use was higher in analyses adjusted for high-dimensional propensity score (HR, 1.16). The risk was also higher in two-stage residual inclusion estimation (HR, 1.21) and in 1:1 time-dependent propensity score-matched cohort (HR, 1.34). The investigators also found that mortality risk was higher for PPI use vs no PPI use (HR, 1.15) and for PPI use vs no PPI and H2 blockers (HR, 1.23).
In addition, mortality risk associated with PPI use was higher in participants without gastrointestinal conditions in the PPI vs H2 blocker cohort (HR, 1.24), the PPI use vs no PPI use cohort (HR, 1.19), and the PPI use vs no PPI and H2 blockers cohort (HR, 1.22). The researchers also observed a graded association between duration of exposure and risk of death among new PPI users.
“The consistency of study findings in our report and the growing body of evidence in the literature showing a host of adverse events associated with PPI use are compelling, and because of the high prevalence of PPI use, it may have public health implications,” the study authors concluded. “Exercising pharmacovigilance and limiting PPI use to instances and durations where it is medically indicated may be warranted.”
- Xie Y, Bowe B, Li T, Xian H, Yan Y, Al-Aly Z. Risk of death among users of proton pump inhibitors: a longitudinal observational cohort study of United States veterans. BMJ Open. 2017. doi:10.1136/bmjopen-2016-015735