Proton Pump Inhibitors Versus Histamine-2 Receptor Antagonists Likely Increase Mortality in Critical Care: An Updated Meta-Analysis

Abstract

Background: Upper gastrointestinal bleeding is common among the critically ill. Recently, the Proton Pump Inhibitors (PPIs) vs. Histamine-2 Receptor Blockers for Ulcer Prophylaxis Therapy in the Intensive Care Unit (PEPTIC) trial suggested PPIs might increase mortality. We performed an updated meta-analysis to further inform discussion.

Methods: We leveraged 2 recent systematic reviews to identify randomized controlled trials directly comparing PPIs and H-2 Receptor Antagonists (H2RAs) for stress ulcer prophylaxis in critically ill patients and reporting mortality. We extracted mortality data from each study and meta-analyzed them with the PEPTIC trial using a random effects model.

Results: Of 28,559 total patients, 14,436 (50.5%) were allocated to PPI and 14,123 to H2RAs (49.5%). Compared to H2RAs, the pooled relative risk for mortality was 1.05 (95% confidence interval 1.00-1.10) with an estimated risk difference for mortality of 9 additional deaths per 1000 patients exposed to PPI (95% confidence interval 0-18); heterogeneity was low (I² = 0%; P = 0.826).

Conclusions: Stress ulcer prophylaxis with PPIs likely increases mortality compared to H2RAs. Whether stress ulcer prophylaxis is beneficial in critical care remains open to further study.

Keywords: Critical care; Histamine-2 receptor antagonists; Mortality; Proton pump inhibitors; Stress ulcer prophylaxis.