Proton pump inhibitors vs. 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 (H2RAs) 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 two recent systematic reviews to identify randomized controlled trials directly comparing PPIs and 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 28559 total patients, 14436 (50.5%) were allocated to PPI and 14123 to H2RAs (49.5%). Compared to H2RAs, the pooled relative risk for mortality was 1.05 (95%CI 1.00 – 1.10) with an estimated risk difference for mortality of 9 additional deaths per 1000 patients exposed to PPI (95%CI 0 to 18); heterogeneity was low (I-squared 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.