Defining Appropriate Use of Proton-Pump Inhibitors Among Medical Inpatients

Abstract

Background: Proton-pump inhibitors (PPIs) are commonly used among medical inpatients, both for prophylaxis against upper gastrointestinal bleeding (UGIB) and continuation of outpatient use. While PPIs reduce the risk of UGIB, they also appear to increase the risk of hospital-acquired pneumonia (HAP) and Clostridium difficile infection (CDI). Depending upon the underlying risks of these conditions and the changes in those risks with PPIs, use of proton-pump inhibitors may lead to a net benefit or net harm among medical inpatients.

Objective: We aimed to determine the net impact of PPIs on hospital mortality among medical inpatients.

Design: A microsimulation model, using literature-derived estimates of the risks of UGIB, HAP, and CDI among medical inpatients, along with the changes in risk associated with PPI use for each of these outcomes. The primary outcome was change in inpatient mortality.

Participants: Simulated general medical inpatients outside the intensive care unit (ICU).

Main measure: Change in overall mortality during hospitalization.

Key results: New initiation of PPI therapy led to an increase in hospital mortality in about 90% of simulated patients. Continuation of outpatient PPI therapy on admission led to net increase in hospital mortality in 79% of simulated patients. Results were robust to both one-way and multivariate sensitivity analyses, with net harm occurring in at least two-thirds of patients in all scenarios.

Conclusions: For the majority of medical inpatients outside the ICU, use of PPIs likely leads to a net increase in hospital mortality. Even in patients at particularly high risk of UGIB, only those at the very lowest risk of HCAP and CDI should be considered for prophylactic PPI use. Continuation of outpatient PPIs may also increase expected hospital mortality. Apart from patients with active UGIB, use of PPIs in hospitalized patients should be discouraged.

Keywords: hospital medicine; medical decision making; modeling; simulation.

Figure 1

Density plot of change in expected mortality with newly-initiated PPI, assuming increased risk of CDI with acid suppression (black) and assuming no increased risk of CDI (gray). The mean impact of PPI initiation on expected mortality is indicated by dashed vertical lines. Patients to the left of zero receive a net benefit, while patients to the right of zero are harmed.

Figure 2

Density plot of change in expected mortality with continuation of chronic PPI on admission, assuming increased risk of CDI with acid suppression (black) and assuming no increased risk of CDI (gray). The mean impact of PPI continuation on expected mortality is indicated by dashed vertical lines.