Timely Cessation of Proton Pump Inhibitors in Critically Ill Patients Impacts Morbidity and Mortality: A Propensity Score-Matched Cohort Study*

Abstract

OBJECTIVE: Proton pump inhibitors (PPIs) are among the drugs most commonly used in critically ill patients. Although mainly applied temporarily for stress ulcer prophylaxis, their application is frequently not terminated. Potential adverse effects of PPI treatment could impact the outcome in case of unnecessary and, therefore, avoidable long-term continuation. We tested the hypotheses that nonindicated PPI therapy continued beyond hospital discharge is associated with increased morbidity, rehospitalization rate, and mortality. DESIGN: Nationwide retrospective cohort study considering critically ill patients treated on German ICUs between January, 2017, and December, 2018 with a 2-year follow-up. SETTING: A total of 591,207 patient datasets of a German healthcare insurer were screened. PATIENTS: We identified 11,576 ICU patients who received PPI therapy for the first time during their index ICU stay without having an indication for its continuation. INTERVENTIONS: The cohort was stratified into two groups: 1) patients without further PPI therapy and 2) patients with continuation of PPI therapy beyond 8 weeks after hospital discharge. MEASUREMENTS AND MAIN RESULTS: Frequency of predescribed adverse events associated with PPI therapy, 1-year rehospitalization rate, and 2-year mortality were determined. The proportion of patients with continued PPI therapy without an objectifiable indication was 41.7% (4,825 of 11,576 patients). These patients had a 27% greater risk of pneumonia (odds ratio [OR] 1.27; 95% CI, 1.15–1.39; p < 0.001) and a 17% greater risk of cardiovascular events (OR 1.17; 95% CI, 1.08–1.26; p < 0.001). Continued PPI therapy was associated with a 34% greater risk of rehospitalization (OR 1.34; 95% CI, 1.23–1.47) and a nearly 20% greater 2-year mortality risk (hazard ratio 1.17; 95% CI, 1.08–1.27; p = 0.006). CONCLUSIONS: These data demonstrate that an unnecessary continuation of PPI therapy after hospital discharge may significantly impact morbidity and mortality. To avoid potentially harmful overuse of a PPIs, intensivists should ensure timely cessation of a temporarily indicated PPI therapy.