Paul Reynolds, BCCCP, PharmD
Assistant Professor
University of Colorado Skaggs School of Pharmacy
Denver, CO, United States
Disclosure information not submitted.
Lauren Wells, PharmD
PharmD
University of Colorado Hospital, United States
Disclosure information not submitted.
Marissa Powell, PharmD
PharmD
University of Colorado Hospital, United States
Disclosure information not submitted.
Robert MacLaren, MPH, PharmD
University of Colorado Skaggs School of Pharmacy
Aurora, CO
Disclosure information not submitted.
Title: Risks and Benefits of Proton Pump Inhibitor Therapy for Stress Ulcer Prophylaxis: A Meta-Analysis
Introduction: Recent studies have shown trends towards an increased mortality, but a reduction in bleeding with proton pump inhibitor use for stress ulcer prophylaxis in the critically ill patient.
Study
Objective: The purpose of this study is to systematically evaluate the risks and benefits of proton pump inhibitor (PPI) use for stress ulcer prophylaxis in the critically ill patient.
Methods: Systematic review and meta-analysis of randomized trials and cohort studies with trial sequential analysis (TSA). Key secondary outcomes included pneumonia (PNA) and Clostridioides difficile associated diarrhea (CDAD).
Results: A total of 68,912 critically ill adults receiving PPIs vs. any comparator were included in this study. PPI use was associated with a trend towards an increased risk of mortality (16.7% PPI vs 15.3% comparator; RR 1.06 95% CI 0.99-1.14; P=0.10) which was significant across randomized studies (19.4% PPI vs 18.7% comparator; RR 1.05 95% CI 1.0-1.09; P=0.04) but not cohort studies (14.2% PPI vs 12.2% comparator; RR 1.04 95% CI 0.87-1.26; P=0.66). Studies with higher baseline severity of illness revealed the greatest mortality risk with PPI use (32.1% PPI vs 29.4% comparator; RR 1.09 95% CI 1.04-1.14; P< 0.001). Mortality TSA results did not show significance but the fragility index was 287. PPI use reduced clinically important bleeding in randomized studies (1.4% PPI vs 2.1% any comparator; RR 0.67 95% CI 0.5-0.9; P=0.009) but not in cohort studies (2.8% PPI vs 1.4% comparator; RR 1.52 95% CI 0.9-2.55; P=0.11) or when compared with histamine-2 receptor antagonists (P=0.09). PPI use increased risk of PNA across all studies (19.9% PPI vs 17.7% comparator; RR 1.16 95% CI 1.03-1.3; P=0.01) but was not associated with an increase in the risk of CDAD.
Conclusion: This meta-analysis demonstrated an associated mortality risk with PPI use, especially in patients with higher severity of illness.