- For critically ill patients, proton pump inhibitors (PPIs) and histamine-2 receptor blockers (H2RBs) were associated with similar mortality rates when prescribed to prevent stress ulcers.
- Editorial discusses limitations relating to:
- High crossover rates.
- Cluster-level data limited on, e.g., infections.
- Possible mortality signal lacks clear mechanism.
Why this matters
- Safety of PPIs vs H2RBs for critically ill has been unclear.
- PPIs have been linked to important harms.
- PPI vs H2RB:
- Mortality: 18.3% vs 17.5%; risk ratio (RR), 1.05 (95% CI, 1.00-1.10; P=.054).
- Clinically important upper gastrointestinal bleeding: 1.3% vs 1.8%; RR, 0.73 (95% CI, 0.57-0.92).
- Similar rates of Clostridioides difficile infection; ICU, hospital lengths of stay.
- International pragmatic randomized open-label registry-embedded cluster crossover PEPTIC trial (n=26,828).
- For critically ill patients receiving mechanical ventilation, 50 ICUs were randomly assigned to give PPI vs H2RB for gastrointestinal prophylaxis.
- After 6 months, ICUs switched to other drug.
- Clinicians could override randomization, switch patients to other drug.
- Outcome: 90-day in-hospital mortality.
- Funding: Commonwealth governments and/or nonprofits.
- Crossover rates:
- H2RB-to-PPI: 20.1%.
- PPI-to-H2RB: 4.1%.
- Potential indication bias “might have masked higher mortality from [PPIs] and attenuated the benefit of a [PPI] strategy on clinically important upper gastrointestinal bleeding,” editor argues.