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

doi:10.1056/EVIDoa2400134

Meta-Analysis

. 2024 Jul;3(7):EVIDoa2400134.

doi: 10.1056/EVIDoa2400134. Epub 2024 Jun 14.

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

Ying Wang¹, Sameer Parpia², Long Ge³, Diane Heels-Ansdell¹, Honghao Lai³, Meisam Abdar Esfahani¹, Bei Pan⁴, Waleed Alhazzani^{1

2}, Stefan Schandelmaier^{5

6

7}, Francois Lauzier^{8

9}, Yaseen Arabi¹⁰, Jeffrey Barletta¹¹, Adam Deane¹², Simon Finfer^{13

14

15}, David Williamson^{16

17}, Salmaan Kanji^{18

19}, Morten H Møller^{20

21}, Anders Perner^{20

21}, Mette Krag^{21

22}, Paul J Young^{23

24}, Joanna C Dionne^{1

25

26}, Naomi Hammond^{27

28}, Zhikang Ye¹, Quazi Ibrahim¹, Deborah Cook^{1

29}

Affiliations

¹ Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada.
² Department of Oncology, McMaster University, Hamilton, ON, Canada.
³ Evidence-based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou, China.
⁴ Center of Evidence-Based Medicine, School of Basic Medical Science, Lanzhou University, Lanzhou, China.
⁵ Division of Clinical Epidemiology, University Hospital and University of Basel, Basel, Switzerland.
⁶ School of Public Health, University College Cork, Cork, Ireland.
⁷ MTA-PTE Lendület "Momentum" Evidence in Medicine Research Group, Medical School, University of Pécs, Pécs, Hungary.
⁸ Population Health and Optimal Health Practice Research Unit (Trauma-Emergency-Critical Care Medicine), CHU de Québec-Université Laval Research Centre, Québec City, QC, Canada.
⁹ Department of Medicine, Department of Anesthesiology and Critical Care, Université Laval, Québec, QC, Canada.
¹⁰ Intensive Care Department, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.
¹¹ Department of Pharmacy Practice, College of Pharmacy, Midwestern University, Glendale, AZ.
¹² Department of Critical Care, Melbourne Medical School, University of Melbourne, Melbourne, VIC, Australia.
¹³ The George Institute for Global Health, Sydney, NSW, Australia.
¹⁴ University of New South Wales, Sydney, NSW, Australia.
¹⁵ School of Public Health, Imperial College London, London, UK.
¹⁶ Pharmacy Department, Université de Montréal, Montréal, QC, Canada.
¹⁷ Pharmacy Department and Research Centre, CIUSSS-NIM Hôpital du Sacré-Cœur de Montréal, Montréal, QC, Canada.
¹⁸ Division of Critical Care, Department of Medicine, University of Ottawa, Ottawa, ON, Canada.
¹⁹ Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
²⁰ Department of Intensive Care, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
²¹ Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
²² Department of Anaesthesia, Centre of Head and Orthopaedics, Rigshospitalet, Copenhagen, Denmark.
²³ Medical Research Institute of New Zealand, Wellington, New Zealand.
²⁴ Intensive Care Unit, Wellington Hospital, Wellington, New Zealand.
²⁵ Divisions of Critical Care Medicine and Gastroenterology, McMaster University, Hamilton, ON, Canada.
²⁶ Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada.
²⁷ Critical Care Program, The George Institute for Global Health and UNSW Sydney, NSW, Australia.
²⁸ Malcolm Fisher Department of Intensive Care, Royal North Shore Hospital, Sydney, NSW, Australia.
²⁹ Department of Medicine, McMaster University, Hamilton, ON, Canada.

PMID: 38874580
DOI: 10.1056/EVIDoa2400134

Meta-Analysis

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

Ying Wang et al. NEJM Evid. 2024 Jul.

. 2024 Jul;3(7):EVIDoa2400134.

doi: 10.1056/EVIDoa2400134. Epub 2024 Jun 14.

Authors

Affiliations

¹ Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada.
² Department of Oncology, McMaster University, Hamilton, ON, Canada.
³ Evidence-based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou, China.
⁴ Center of Evidence-Based Medicine, School of Basic Medical Science, Lanzhou University, Lanzhou, China.
⁵ Division of Clinical Epidemiology, University Hospital and University of Basel, Basel, Switzerland.
⁶ School of Public Health, University College Cork, Cork, Ireland.
⁷ MTA-PTE Lendület "Momentum" Evidence in Medicine Research Group, Medical School, University of Pécs, Pécs, Hungary.
⁸ Population Health and Optimal Health Practice Research Unit (Trauma-Emergency-Critical Care Medicine), CHU de Québec-Université Laval Research Centre, Québec City, QC, Canada.
⁹ Department of Medicine, Department of Anesthesiology and Critical Care, Université Laval, Québec, QC, Canada.
¹⁰ Intensive Care Department, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.
¹¹ Department of Pharmacy Practice, College of Pharmacy, Midwestern University, Glendale, AZ.
¹² Department of Critical Care, Melbourne Medical School, University of Melbourne, Melbourne, VIC, Australia.
¹³ The George Institute for Global Health, Sydney, NSW, Australia.
¹⁴ University of New South Wales, Sydney, NSW, Australia.
¹⁵ School of Public Health, Imperial College London, London, UK.
¹⁶ Pharmacy Department, Université de Montréal, Montréal, QC, Canada.
¹⁷ Pharmacy Department and Research Centre, CIUSSS-NIM Hôpital du Sacré-Cœur de Montréal, Montréal, QC, Canada.
¹⁸ Division of Critical Care, Department of Medicine, University of Ottawa, Ottawa, ON, Canada.
¹⁹ Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
²⁰ Department of Intensive Care, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
²¹ Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
²² Department of Anaesthesia, Centre of Head and Orthopaedics, Rigshospitalet, Copenhagen, Denmark.
²³ Medical Research Institute of New Zealand, Wellington, New Zealand.
²⁴ Intensive Care Unit, Wellington Hospital, Wellington, New Zealand.
²⁵ Divisions of Critical Care Medicine and Gastroenterology, McMaster University, Hamilton, ON, Canada.
²⁶ Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada.
²⁷ Critical Care Program, The George Institute for Global Health and UNSW Sydney, NSW, Australia.
²⁸ Malcolm Fisher Department of Intensive Care, Royal North Shore Hospital, Sydney, NSW, Australia.
²⁹ Department of Medicine, McMaster University, Hamilton, ON, Canada.

PMID: 38874580
DOI: 10.1056/EVIDoa2400134

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

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

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