Proton-Pump Inhibitors to Prevent Gastrointestinal Bleeding - An Updated Meta-Analysis.

Wang, Ying and Parpia, Sameer and Ge, Long and Heels-Ansdell, Diane and Lai, Honghao and Esfahani, Meisam Abdar and Pan, Bei and Alhazzani, Waleed and Schandelmaier, Stefan and Lauzier, Francois and Arabi, Yaseen and Barletta, Jeffrey and Deane, Adam and Finfer, Simon and Williamson, David and Kanji, Salmaan and Møller, Morten H and Perner, Anders and Krag, Mette and Young, Paul J and Dionne, Joanna C and Hammond, Naomi and Ye, Zhikang and Ibrahim, Quazi and Cook, Deborah (2024) Proton-Pump Inhibitors to Prevent Gastrointestinal Bleeding - An Updated Meta-Analysis. NEJM EVIDENCE, 3 (7). EVIDoa2400134. ISSN 2766-5526

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Abstract

BACKGROUND The goal of this systematic review was to examine the efficacy and safety of proton-pump inhibitors for stress ulcer prophylaxis in critically ill patients. METHODS We included randomized trials comparing proton-pump inhibitors versus placebo or no prophylaxis in critically ill adults, performed meta-analyses, and assessed certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations approach. To explore the effect of proton-pump inhibitors on mortality based on disease severity, a subgroup analysis was conducted combining within-trial subgroup data from the two largest trials and assessed credibility using the Instrument for Assessing the Credibility of Effect Modification Analyses. RESULTS Twelve trials that enrolled 9533 patients were included. Proton-pump inhibitors were associated with a reduced incidence of clinically important upper gastrointestinal bleeding (relative risk [RR], 0.51 [95% confidence interval (CI), 0.34 to 0.76]; high certainty evidence). Proton-pump inhibitors may have little or no effect on mortality (RR, 0.99 [95% CI, 0.93 to 1.05]; low certainty). Within-trial subgroup analysis with intermediate credibility suggested that the effect of proton-pump inhibitors on mortality may differ based on disease severity. Subgroup results raise the possibility that proton-pump inhibitors may decrease 90-day mortality in less severely ill patients (RR, 0.89; 95% CI, 0.80 to 0.98) and may increase mortality in more severely ill patients (RR, 1.08; 95% CI, 0.96 to 1.20]. Proton-pump inhibitors may have no effect on pneumonia and little or no effect on infection (low certainty). CONCLUSIONS High certainty evidence supports the association of proton-pump inhibitors with decreased upper gastrointestinal bleeding. Proton-pump inhibitors may have little or no effect on mortality, although a decrease in mortality in less severely ill patients and an increase in mortality in more severely ill patients remain possible. (PROSPERO number CRD42023461695.).

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