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

• Published in: BMJ (Online) 2019-05, Vol.365, p.l1580-l1580
• Main Authors: Xie, Yan, Bowe, Benjamin, Yan, Yan, Xian, Hong, Li, Tingting, Al-Aly, Ziyad
• Format: Article
• Language: English
• Subjects: Acids; Aged; Cancer; Cancer therapies; Cardiovascular diseases; Cardiovascular Diseases - mortality; Cause of Death; Circulatory system; Cohort analysis; Cohort Studies; Data warehouses; Death; Female; Gastric cancer; Gastrointestinal Neoplasms - mortality; Humans; Kidney diseases; Laboratories; Longitudinal Studies; Male; Middle Aged; Mortality; Parasitic diseases; Peptic Ulcer - prevention & control; Prescription drugs; Proton pump inhibitors; Proton Pump Inhibitors - therapeutic use; Renal Insufficiency, Chronic - mortality; Risk Factors; United States - epidemiology; Veterans; Veterans Health - statistics & numerical data; Vigilance
• ISSN: 0959-8138; 1756-1833
• DOI: 10.1136/bmj.l1580

AbstractObjectiveTo estimate all cause mortality and cause specific mortality among patients taking proton pump inhibitors (PPIs).DesignLongitudinal observational cohort study.SettingUS Department of Veterans Affairs.ParticipantsNew users of PPIs (n=157 625) or H2 blockers (n=56 842).Main outcome measuresAll cause mortality and cause specific mortality associated with taking PPIs (values reported as number of attributable deaths per 1000 patients taking PPIs).ResultsThere 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).ConclusionsTaking 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.