Patients in both primary and secondary cohorts were followed until 30 September 2013 or death.The study was approved by the Institutional Review Board of the VA Saint Louis Health Care System, Saint Louis, Missouri.We additionally built two secondary cohorts to examine the association of PPI use and risk of death in (a) PPI versus no PPI users and (b) PPI versus non-users of acid suppression therapy.
We used the Department of Veterans Affairs databases, including inpatient and outpatient medical SAS data sets (that include utilisation of data related to all inpatient and outpatient encounters within the VA system), to ascertain detailed patient demographic characteristics and comorbidity information based on inpatient and outpatient encounters.2 24 The VA Managerial Cost Accounting System Laboratory Results (a comprehensive database that includes VA-wide results for selected laboratory tests obtained in the clinical setting) provided information on outpatient and inpatient laboratory results.
The VA Corporate Data Warehouse Production Outpatient Pharmacy domain provided information on outpatient prescriptions.
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.
The VA Vital Status and Beneficiary Identification Records Locator Subsystem files provided demographic characteristics and death. Once cohort participants received PPI prescription, they were considered with the effect of PPI until the end of follow-up.
Medications that contain esomeprazole, lansoprazole, omeprazole, pantoprazole or rabeprazole were counted as PPI.
Using administrative data from the US Department of Veterans Affairs, we identified patients who received an outpatient H2 blockers or PPI prescription between 1 October 2006 and 30 September 2008 (n=1 762 908).
In order to select new users of acid suppression therapy (incident user design), we excluded 1 356 948 patients who received any outpatient H2 blockers or PPI prescriptions between 1 October 1998 and 30 September 2006.
Among new PPI users, there was a graded association between the duration of exposure and the risk of death.