Prescribing, deprescribing and potential adverse effects of proton pump inhibitors in older patients with multimorbidity: an observational study

Abstract

Background: Proton pump inhibitors (PPIs) contribute to polypharmacy and are associated with adverse effects. As prospective data on longitudinal patterns of PPI prescribing in older patients with multimorbidity are lacking, we sought to assess patterns of PPI prescribing and deprescribing, as well as the association of PPI use with hospital admissions over 1 year in this population.

Methods: We conducted a prospective, longitudinal cohort study using data from the Optimizing Therapy to Prevent Avoidable Hospital Admissions in Multimorbid Older Adults (OPERAM) trial, a randomized controlled trial testing an intervention to reduce inappropriate prescribing (2016-2018). This trial included adults aged 70 years and older with at least 3 chronic conditions and prescribed at least 5 chronic medications. We assessed prevalence of PPI use at time of hospital admission, and new prescriptions and deprescribing at discharge, and at 2 months and 1 year after discharge, by intervention group. We used a regression with competing risk for death to assess the association of PPI use with readmissions related to their potential adverse effects, and all-cause readmission.

Results: Overall, 1080 (57.4%) of 1879 patients (mean age 79 yr) had PPI prescriptions at admission, including 496 (45.9%) patients with a potentially inappropriate indication. At discharge, 133 (24.9%) of 534 patients in the intervention group and 92 (16.8%) of 546 patients in the control group who were using PPIs at admission had deprescribing. Among 680 patients who were not using PPIs at discharge, 47 (14.6%) of 321 patients in the intervention group and 40 (11.1%) of 359 patients in the control group had a PPI started within 2 months. Use of PPIs was associated with all-cause readmission (n = 770, subdistribution hazard ratio 1.31, 95% confidence interval 1.12-1.53).

Interpretation: Potentially inappropriate use of PPI, new PPI prescriptions and PPI deprescribing were frequent among older adults with multimorbidity and polypharmacy. These data suggest that persistent PPI use may be associated with clinically important adverse effects in this population.

Figure 1:

Longitudinal patterns of proton pump inhibitor (PPI) prescribing and deprescribing among patients in intervention group. (A) Patterns of PPI prescribing and deprescribing among patients using PPIs at admission, from admission to discharge. (B) Patterns of PPI prescribing and deprescribing among patients not using PPIs at admission, from admission to discharge. (C) Patterns of deprescribing among patients with PPI prescriptions at admission, and of prescribing among patients without prescriptions at admission, from discharge to 12 months after discharge. Note: Diagnoses were not available after discharge, except among patients with readmissions, so we could not ascertain the potential appropriateness of PPI prescribing at 2 months and 12 months after discharge.

Figure 2:

Longitudinal patterns of proton pump inhibitor (PPI) prescribing and deprescribing among patients in control group. (A) Patterns of PPI prescribing and deprescribing among patients using PPIs at admission, from admission to discharge. (B) Patterns of PPI prescribing and deprescribing among patients not using PPIs at admission, from admission to discharge. (C) Patterns of deprescribing among patients with PPI prescriptions at admission, and of prescribing among patients without prescriptions at admission, from discharge to 12 months after discharge. Note: Diagnoses were not available after discharge, except among patients with readmissions, so we could not ascertain the potential appropriateness of PPI prescribing at 2 months and 12 months after discharge.

Figure 3:

Predicted cumulative incidence of (A) all-cause readmissions, and (B) PPI-related readmissions, and competing risk of death, among patients with or without persistent use of PPIs. Note: CI = confidence interval, n = number of events, PPI = proton pump inhibitor, SHR = subdistribution hazard ratio. Results of competing-risk regression based on the method by Fine and Gray, with death as competing event, adjusted for age, Charlson Comorbidity Index, medication count, study site, admission ward, number of previous hospital admissions, anticoagulant use, intervention arm and discharge destination. Potential PPI-related readmissions included readmissions with pneumonia, fracture, nephritis or bacterial intestinal infection.