Effectiveness and Safety of Proton Pump Inhibitor Deprescribing in Hospitalized Adults: A Systematic Review
Keywords:
Proton Pump Inhibitors, deprescribing, hospitalization, medication review, gastrointestinal bleeding; transitions of careAbstract
Proton pump inhibitors (PPIs) for short-term indications are often ordered to stay on lists after discharge from the hospital and if ordered for an outpatient who was already taking a PPI, there may not be any push back to question the need for the PPI. The aim of this systematic review was to evaluate efficacy and safety of hospital-initiated PPI discontinuation or dose reduction or step down in adults. In the MedSafer trial, PPI deprescribing at discharge was conducted in 222/1056 intervention patients, and 127/1227 controls with a potentially inappropriate PPI (adjusted difference of 9.4 percentage points, 95% CI 2.5–16.4). The medication-targeted alerts were found to increase PPI discontinuation in the acute kidney injury trial within 24 hours (RR 1.26, 95% CI 1.10–1.45). Smaller implementation studies with different definitions of outcome and completeness of follow-up and post-discharge study persistence supported this feasibility. There is a lack of directly relevant information regarding serious bleeding, symptom burden and improvement to patient over the long term. Observational associations between continued PPI exposure and adverse outcomes did not establish benefits of withdrawal. Reviewing PPI treatment in hospital can reduce unnecessary PPI treatment, particularly when care is planned and where there was communication at all points of transfer. Because of indications-based reassessment and monitored withdrawal and the uncertainty of clinical safety and the completeness of report retrieval, we do not recommend a general approach of stopping PPIs in adults with any indications received for hospital admission.
References
1. Targownik LE, Fisher DA, Saini SD. AGA Clinical Practice Update on De-Prescribing of Proton Pump Inhibitors: Expert Review. Gastroenterology. 2022;162(4):1334-1342. https://doi.org/10.1053/j.gastro.2021.12.247
2. Farrell B, Pottie K, Thompson W, Boghossian T, Pizzola L, Rashid FJ, et al. Deprescribing proton pump inhibitors: Evidence-based clinical practice guideline. Can Fam Physician. 2017;63(5):354-364. https://pubmed.ncbi.nlm.nih.gov/28500192/
3. MacLaren R, Dionne JC, Granholm A, Alhazzani W, Szumita PM, Olsen K, et al. Society of Critical Care Medicine and American Society of Health-System Pharmacists Guideline for the Prevention of Stress-Related Gastrointestinal Bleeding in Critically Ill Adults. Crit Care Med. 2024;52(8):e421-e430. https://doi.org/10.1097/ccm.0000000000006330
4. Katz PO, Dunbar KB, Schnoll-Sussman FH, Greer KB, Yadlapati R, Spechler SJ. ACG Clinical Guideline for the Diagnosis and Management of Gastroesophageal Reflux Disease. Am J Gastroenterol. 2022;117(1):27-56. https://doi.org/10.14309/ajg.0000000000001538
5. Boghossian TA, Rashid FJ, Thompson W, Welch V, Moayyedi P, Rojas-Fernandez C, et al. Deprescribing versus continuation of chronic proton pump inhibitor use in adults. Cochrane Database Syst Rev. 2017;3:CD011969. https://doi.org/10.1002/14651858.cd011969.pub2
6. Rossi A, Perrella L, Scotti S, Olmastroni E, Galimberti F, Ardoino I, et al. Approaches to Deprescribing Proton Pump Inhibitors in Clinical Practice: A Systematic Review. J Clin Med. 2024;13(20):6283. https://doi.org/10.3390/jcm13206283
7. Orelio CC, Heus P, Kroese-van Dieren JJ, Spijker R, van Munster BC, Hooft L. Reducing Inappropriate Proton Pump Inhibitors Use for Stress Ulcer Prophylaxis in Hospitalized Patients: Systematic Review of De-Implementation Studies. J Gen Intern Med. 2021;36(7):2065-2073. https://doi.org/10.1007/s11606-020-06425-6
8. McDonald EG, Wu PE, Rashidi B, Wilson MG, Bortolussi-Courval É, Atique A, et al. The MedSafer Study-Electronic Decision Support for Deprescribing in Hospitalized Older Adults: A Cluster Randomized Clinical Trial. JAMA Intern Med. 2022;182(3):265-273. https://doi.org/10.1001/jamainternmed.2021.7429
9. Moryousef J, Bortolussi-Courval É, Podymow T, Lee TC, Trinh E, McDonald EG. Deprescribing Opportunities for Hospitalized Patients With End-Stage Kidney Disease on Hemodialysis: A Secondary Analysis of the MedSafer Cluster Randomized Controlled Trial. Can J Kidney Health Dis. 2022;9:20543581221098778. https://doi.org/10.1177/20543581221098778
10. McDonald EG, Wu PE, Rashidi B, Forster AJ, Huang A, Pilote L, et al. The MedSafer Study: A Controlled Trial of an Electronic Decision Support Tool for Deprescribing in Acute Care. J Am Geriatr Soc. 2019;67(9):1843-1850. https://doi.org/10.1111/jgs.16040
11. Wilson FP, Yamamoto Y, Martin M, Coronel-Moreno C, Li F, Cheng C, et al. A randomized clinical trial assessing the effect of automated medication-targeted alerts on acute kidney injury outcomes. Nat Commun. 2023;14(1):2826. https://doi.org/10.1038/s41467-023-38532-3
12. Aubert CE, Blum MR, Gastens V, Dalleur O, Vaillant F, Jennings E, et al. Prescribing, deprescribing and potential adverse effects of proton pump inhibitors in older patients with multimorbidity: an observational study. CMAJ Open. 2023;11(1):E170-E178. https://doi.org/10.9778/cmajo.20210240
13. Calvini G, Baiardi G, Mattioli F, Milano G, Calautti F, Zunino A, et al. Deprescribing Strategies: A Prospective Study on Proton Pump Inhibitors. J Clin Med. 2023;12(8):3029. https://doi.org/10.3390/jcm12083029
14. Baiardi G, Calvini G, Panarello S, Fioravanti C, Stella M, Martelli A, et al. Prescriptive Appropriateness: Inhospital Adherence to Proton Pump Inhibitors Deprescription Flow Chart. Pharmaceuticals (Basel). 2023;16(5):635. https://doi.org/10.3390/ph16050635
15. Dumlu HI, Sancar M, Ozdemir A, Okuyan B. Impact of a clinical pharmacist-led stewardship program for the appropriate use of acid suppression therapy in older hospitalized patients: a non-randomized controlled study. Int J Clin Pharm. 2022;44(4):914-921. https://doi.org/10.1007/s11096-022-01394-8
16. McDonald EG, Jones J, Green L, Jayaraman D, Lee TC. Reduction of inappropriate exit prescriptions for proton pump inhibitors: A before-after study using education paired with a web-based quality-improvement tool. J Hosp Med. 2015;10(5):281-286. https://doi.org/10.1002/jhm.2330
17. Luc MTK, Adi-Pranoto E, Lau D, Anpalahan M. Outcomes of de-prescribing proton pump inhibitors during acute admissions in a general medical unit: a pilot study. Intern Med J. 2023;53(6):1061-1064. https://doi.org/10.1111/imj.16123
18. Tan CJY, Lee SX, Ng TM. The impact of deprescribing interventions on oral proton pump inhibitor utilisation in a Singapore tertiary hospital: A quality improvement initiative. Ann Acad Med Singap. 2022;51(1):8-15. https://doi.org/10.47102/annals-acadmedsg.2021308
19. Xin C, Dong Z, Lin M, Li GH. The impact of pharmaceutical interventions on the rational use of proton pump inhibitors in a Chinese hospital. Patient Prefer Adherence. 2018;12:21-26. https://doi.org/10.2147/ppa.s150388
20. Masood U, Sharma A, Bhatti Z, Carroll J, Bhardwaj A, Sivalingam D, et al. A Successful Pharmacist-Based Quality Initiative to Reduce Inappropriate Stress Ulcer Prophylaxis Use in an Academic Medical Intensive Care Unit. Inquiry. 2018;55:0046958018759116. https://doi.org/10.1177/0046958018759116
21. Liput SA, Ryder LP, Jordan TA, Gerlach AT. Stress ulcer prophylaxis upon discharge from intensive care units in an academic medical center. Int J Acad Med. 2018;4(2):105–111. https://doi.org/10.4103/ijam.ijam_64_17
22. Marín-Gorricho R, Lozano C, Torres C, Ramalle-Gómara E, Hurtado-Gómez MF, Pérez-Zuazo R, et al. [Impact of pharmaceutical care in polymedicated patients admitted to a geriatric ward]. An Sist Sanit Navar. 2022;45(1):e0990. https://doi.org/10.23938/assn.0990
23. Barraquer Comes A, Roy Millán P. Proton Pump Inhibitor Deprescription Prospective Study in Patients Without Indication: Are There Differences in Proportion of Restarts According to Withdrawal Strategy? J Pharm Technol. 2023;39(5):224-230. https://doi.org/10.1177/87551225231195216
24. Mersfelder TL, Jacob C, Lam JK, Kavanaugh KJ, Molnar CM. Evaluation of a Pharmacist-Driven Protocol to Reduce Inappropriate Use of Acid-Suppressive Medications In the Non-ICU Setting. P T. 2019;44(8):471-473. https://pubmed.ncbi.nlm.nih.gov/31447534/
25. Wahking RA, Steele RL, Hanners RE, Lockwood SM, Davis KW. Outcomes From a Pharmacist - led Proton Pump Inhibitor Stewardship Program at a Single Institution. Hosp Pharm. 2018;53(1):59-67. https://doi.org/10.1177/0018578717747192
26. Palmowski L, von Busch A, Unterberg M, Bergmann L, Schmitz S, Schlüter A, et al. Timely Cessation of Proton Pump Inhibitors in Critically Ill Patients Impacts Morbidity and Mortality: A Propensity Score-Matched Cohort Study. Crit Care Med. 2024;52(2):190-199. https://doi.org/10.1097/ccm.0000000000006104
27. Bilek AJ, Levy Y, Kab H, Andreev P, Garfinkel D. Teaching physicians the GPGP method promotes deprescribing in both inpatient and outpatient settings. Ther Adv Drug Saf. 2019;10:2042098619895914. https://doi.org/10.1177/2042098619895914
28. Chen X, Hu X, Su Q, Zhu L, Tang Z, Tang C, et al. Medication stewardship by clinical pharmacists in acute ischemic stroke care: a retrospective analysis of drug-related problem reduction and cost-saving outcomes. Front Pharmacol. 2025;16:1608457. https://doi.org/10.3389/fphar.2025.1608457
29. Wang X, McIver DJ, Min H, Guo J, Li H. Evaluating a multifaceted stewardship intervention on proton pump inhibitor utilization: an interrupted time-series analysis of prescribing patterns in a northwest Chinese hospital. Front Pharmacol. 2026;17:1700146. https://doi.org/10.3389/fphar.2026.1700146
30. Naschitz JE, Leibovitz G, Yalonetski I. PPI Deprescribing in the Geriatric Hospital. Is It Worth a Trial? J Med Res Clin Rev. 2025;1(2):1-4. https://doi.org/10.67335/3070-6238.1008
31. Campbell M, McKenzie JE, Sowden A, Katikireddi SV, Brennan SE, Ellis S, et al. Synthesis without meta-analysis (SWiM) in systematic reviews: reporting guideline. BMJ. 2020;368:l6890. https://doi.org/10.1136/bmj.l6890
32. Reimer C, Søndergaard B, Hilsted L, Bytzer P. Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy. Gastroenterology. 2009;137(1):80-7, 87.e1. https://doi.org/10.1053/j.gastro.2009.03.058
33. Mekhail A, Young P, Mekhail AM, Tinawi G, Haran C, Clayton N, et al. Stress Ulcer Prophylaxis in Cardiac Surgery: A Retrospective Cohort Study to Analyze the Effects of SUP Cessation. J Intensive Care Med. 2023;38(10):917-921. https://doi.org/10.1177/08850666231171327
34. Cook D, Deane A, Lauzier F, Zytaruk N, Guyatt G, Saunders L, et al. Stress Ulcer Prophylaxis during Invasive Mechanical Ventilation. N Engl J Med. 2024;391(1):9-20. https://doi.org/10.1056/nejmoa2404245
35. Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898. https://doi.org/10.1136/bmj.l4898
36. Sterne JA, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919. https://doi.org/10.1136/bmj.i4919
37. Balshem H, Helfand M, Schünemann HJ, Oxman AD, Kunz R, Brozek J, et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011;64(4):401-406. https://doi.org/10.1016/j.jclinepi.2010.07.015
38. Wehmeyer MH, Horvatits T, Buchholz A, Krause L, Walter S, Zapf A, et al. Stop of proton-pump inhibitor treatment in patients with liver cirrhosis (STOPPIT): study protocol for a prospective, multicentre, controlled, randomized, double-blind trial. Trials. 2022;23(1):302. https://doi.org/10.1186/s13063-022-06232-w
Published
Issue
Section
License
Copyright (c) 2026 The Author(s)
This work is licensed under a Creative Commons Attribution 4.0 International License.
