Comparative Effectiveness of Proton Pump Inhibitors vs Histamine Type 2 Receptor Blockers for Preventing Clinically Important Gastrointestinal Bleeding During Intensive Care: A Population-Based Study

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Proton pump inhibitors (PPIs) and histamine type 2 receptor blockers (H2Bs) are used for stress ulcer prophylaxis. Although the PPIs have greater potency for acid suppression, their relative effectiveness for preventing clinically important GI bleeding (CIGIB) has not been established. The goal of this study was to determine whether prophylactic PPIs were associated with lower risk of CIGIB than H2Bs among critically ill adults.


This retrospective cohort study included adults with critical illness from January 1, 2008, to June 30, 2012, who had at least one stress ulcer risk factor and received a PPI or H2B for ≥ 3 days. Cox proportional hazards regression propensity score matching and instrumental variable analyses were used to control for selection bias and confounding by unmeasured factors. The Acute Physiology and Chronic Health Evaluation Score version IV score was used to adjust for differences of acuity. The main outcome and exposure was CIGIB.


Among 70,093 patients at risk, 49,576 (70.7%) received prophylaxis for at least 3 days, and 424 patients (0.6%) met the definition for experiencing CIGIB. The hazard for CIGIB was two times greater for PPI users compared with H2B users (adjusted hazard ratio, 1.82 [95% CI, 1.19-2.78]; hazard ratio, 2.37 [95% CI, 1.61-3.5]). Sensitivity analyses failed to detect any plausible scenario in which PPIs were superior to H2Bs for the prevention of CIGIB.


H2Bs were robustly and consistently associated with significantly lower CIGIB risk compared with PPIs in this population.

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