Use of proton pump inhibitors (PPIs) is associated with excess deaths from chronic kidney disease (CKD) and cardiovascular disease (CVD), new findings suggest.

In a new study, taking PPIs was associated with an excess mortality of 4 and 15 per 1000 patients due to CKD and CVD, respectively, Ziyad Al-Aly, MD, of Veterans Affairs St Louis Health Care System, and colleagues reported in the BMJ. Even among a subgroup of patients without a gastrointestinal indication for acid suppression drugs—for whom benefits are uncertain—the investigators found excess mortality of 5, 23, and 3 per 1000 PPI users from CKD, CVD, and upper gastrointestinal cancer, respectively. History of these conditions did not influence results.

“The evidence that mortality due to cardiovascular disease, chronic kidney disease, and upper gastrointestinal cancer was not modified by the presence of baseline cardiovascular disease, chronic kidney disease, or upper gastrointestinal cancer, respectively, suggests the need for heightened vigilance among those with and—with equal importance—those at risk of these conditions,” Dr Al-Aly and colleagues wrote.

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For the study, the team analyzed a cohort of 214,467 United States veterans (mean age 65 years; 96% male; 87% white) initiating an acid suppression drug with more than a 90-day supply. Of these, 157,625 took PPIs and 56,842 histamine H2 receptor antagonists (H2 blockers). Rabeprazole 20 mg once a day, omeprazole 20 mg once a day, and rabeprazole 20 mg twice a day accounted for 59%, 22%, and 8% of all initial PPI prescriptions, respectively.

Overall, 45 excess deaths occurred per 1000 patients taking PPIs over 10 years of follow-up. The investigators attributed 17 excess deaths per 1000 PPI users to circulatory system diseases, 13 to neoplasms, 4 to infectious and parasitic diseases, and 6 to genitourinary system diseases. In analyses of specific causes of death, CKD and CVD were most prominent. PPI use was not associated with increased mortality due to peptic ulcer disease or other digestive system diseases.

Patients who used PPIs for longer periods were at greater risks for all-cause mortality and death from circulatory system diseases, neoplasms, and genitourinary system diseases.

The study authors noted that previous studies have associated PPIs with all-cause mortality as well as development of acute kidney injury, CKD, CVD, gastric cancer, and other conditions.

“The evidence from all available studies suggests that long term PPI use is associated with serious adverse events … PPIs should be used only when medically indicated and for the minimum duration necessary,” Dr Al-Aly’s team concluded.

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Xie Y, Bowe B, Yan Y, et al. Estimates of all cause mortality and cause specific mortality associated with proton pump inhibitors among US veterans: cohort study. BMJ 2019;365:1580. doi:10.1136/bmj.1580