PPI Use May Increase Risk for Mortality from Upper GI Cancer, Other Conditions

Individuals who take proton pump inhibitors (PPIs) or histamine H2 receptor antagonists (H2 blockers) may have an increased risk for cause-specific mortality due to upper gastrointestinal (GI) cancer, cardiovascular disease (CVD), and chronic kidney disease, according to findings from a new study.

Previous research has shown excess risk of all-cause mortality among individuals who take PPIs. Yet, the cause specific mortality attributed to PPI use has remained unknown.

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For this study, the researchers reviewed data from 214,467 veterans in the US Department of Veterans Affairs database who were new users of acid suppression drugs. Participant selection took place between July 1, 2002, and June 30, 2004. A total of 157,625 individuals were taking PPIs and 56,842 were taking H2 blockers.

Individuals took PPIs for conditions such as circulatory system diseases, neoplasms, infectious and parasitic diseases, and genitourinary system diseases.

Results showed 45.20 excess deaths per 1000 individuals taking PPIs. The rate of attributable deaths per 1000 patients, associated with PPI use, was 17.47 for circulatory system diseases, 12.94 for neoplasms, 4.20 for infectious and parasitic diseases, and 6.25 for genitourinary system diseases.

In analyses of subcauses of mortality, PPI use was associated with excess mortality due to CVD and chronic kidney disease; the rate of attributable deaths per 1000 patients was 15.48 for CVD and 4.19 for kidney disease.

Among 116,377 individuals without a documented indication for acid suppression therapy, PPI use was associated with excess mortality due to upper GI cancer, CVD, and chronic kidney disease, with rates of attributable deaths per 1000 patients of 3.12, 22.91, and 4.74, respectively.

PPI use was not associated with an excess burden of transportation-related mortality or mortality to peptic ulcer disease.

“Heightened vigilance in the use of PPI may be warranted,” the researchers concluded.

—Melinda Stevens

Reference:

Xie Y, Bowe B, Yan Y, Xian H, Li T, Al-Aly Z. Estimates of all cause mortality and cause specific mortality associated with proton pump inhibitors among US veterans: cohort study [published online May 30, 2019]. BMJ. doi:10.1136/bmj.l1580.