Effective and safe proton pump inhibitor therapy in acid-related diseases – A position paper addressing benefits and potential harms of acid suppression
Open accessAbstract
BACKGROUND: The introduction of proton pump inhibitors (PPIs) into clinical practice has revolutionized the management of acid-related diseases. Studies in primary care and emergency settings suggest that PPIs are frequently prescribed for inappropriate indications or for indications where their use offers little benefit. Inappropriate PPI use is a matter of great concern, especially in the elderly, who are often affected by multiple comorbidities and are taking multiple medications, and are thus at an increased risk of long-term PPI-related adverse outcomes as well as drug-to-drug interactions. Herein, we aim to review the current literature on PPI use and develop a position paper addressing the benefits and potential harms of acid suppression with the purpose of providing evidence-based guidelines on the appropriate use of these medications. METHODS: The topics, identified by a Scientific Committee, were assigned to experts selected by three Italian Scientific Societies, who independently performed a systematic search of the relevant literature using Medline/PubMed, Embase, and the Cochrane databases. Search outputs were distilled, paying more attention to systematic reviews and meta-analyses (where available) representing the best evidence. The draft prepared on each topic was circulated amongst all the members of the Scientific Committee. Each expert then provided her/his input to the writing, suggesting changes and the inclusion of new material and/or additional relevant references. The global recommendations were then thoroughly discussed in a specific meeting, refined with regard to both content and wording, and approved to obtain a summary of current evidence. RESULTS: Twenty-five years after their introduction into clinical practice, PPIs remain the mainstay of the treatment of acid-related diseases, where their use in gastroesophageal reflux disease, eosinophilic esophagitis, Helicobacter pylori infection, peptic ulcer disease and bleeding as well as, and Zollinger-Ellison syndrome is appropriate. Prevention of gastroduodenal mucosal lesions (and symptoms) in patients taking non-steroidal anti-inflammatory drugs (NSAIDs) or antiplatelet therapies and carrying gastrointestinal risk factors also represents an appropriate indication. On the contrary, steroid use does not need any gastroprotection, unless combined with NSAID therapy. In dyspeptic patients with persisting symptoms, despite successful H. pylori eradication, short-term PPI treatment could be attempted. Finally, addition of PPIs to pancreatic enzyme replacement therapy in patients with refractory steatorrhea may be worthwhile. CONCLUSIONS: Overall, PPIs are irreplaceable drugs in the management of acid-related diseases. However, PPI treatment, as any kind of drug therapy, is not without risk of adverse effects. The overall benefits of therapy and improvement in quality of life significantly outweigh potential harms in most patients, but those without clear clinical indication are only exposed to the risks of PPI prescription. Adhering with evidence-based guidelines represents the only rational approach to effective and safe PPI therapy. Please see related Commentary: doi: 10.1186/s12916-016-0724-1 .
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PPIs have unfavorable effects on gastric functions and host defensive mechanisms, causing delayed gastric emptying, decreased gastric mucus viscosity, increased bacterial load and increased bacterial translocation.
“PPIs have unfavorable effects on gastric functions and host defensive mechanisms, causing delayed gastric emptying, decreased gastric mucus viscosity, increased bacterial load and increased bacterial translocation[55-57].”
From Proton pump inhibitors and dysbiosis: current knowledge and aspects to be clarified (2019) · cites this paper as [55]
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References 507 · Cited by 469
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- [72]Edwards SJ Lind T Lundell L Systematic review of proton pump inhibitors for the maintenance of healed reflux oesophagitis J Outc Resear. 2002 6 1 14
- [78]Yuan Y Dattani ND Scarpignato C Hunt RH Use of antisecretory medication (ARM) after antireflux surgery (ARS) for patients with gastroesophageal reflux disease (GERD): a systematic review of non-randomized studies Gut. 2010 59 Suppl 1 A116 7
- [219]Scarpignato C, Pelosini I, Contini S. What is the effect of acid suppression with proton pump inhibitors on esophageal and gastric motility? In: Giuli R et al. Editor. The Duodenogastroesophageal Reflux – From the Duodenum to the Trachea: 125 Questions, 125 Answers. John Libbey Eurotext; 2006. pp. 262–71.
- [464]Scarpignato C, Bertelé A. Effect of proton pump inhibitors on gut microbiota. Biotascope. 2016. In press.
- Authors
- for the SIF-AIGO-FIMMG Group, Scarpignato, C., on behalf of the Italian Society of Pharmacology, T. I. A. O. H. G., Gatta, L., Zullo, A., & Blandizzi, C.
- Affiliations
- University of Parma (IT)
- University of Pisa (IT)
- Corresponding author
- Scarpignato, Carmelo
- Venue
- BMC Medicine
- Published
- 2016-11-09
- Volume
- 14
- Issue
- 1
- Pages
- 179-179
- ISSN
- 1741-7015 (ISSN-L)
- PMC
- PMC5101793
- OpenAlex
- W2554833894
- Cited by
- 469
- References
- 507
- Citations by year
- 2026: 37 · 2025: 48 · 2024: 52 · 2023: 66 · 2022: 52 · 2021: 41 · 2020: 50 · 2019: 29 · 2018: 55 · 2017: 38 · 2016: 1
- FWCI
- 44.88
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- BMC Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion, cc-by)
- Funders
- Ottawa Hospital Research Institute
- McMaster University
- Université de Nantes
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK102981)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastroesophageal reflux and treatments
- Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
- Health Sciences › Medicine › Surgery › Helicobacter pylori-related gastroenterology studies
- Keywords
- proton pump inhibitors, acid-related diseases, acid suppression, inappropriate prescribing, drug interactions, gastroesophageal reflux disease, eosinophilic esophagitis, Helicobacter pylori infection, peptic ulcer, Zollinger-Ellison syndrome, NSAID-induced gastropathy, antiplatelet therapy, dyspepsia, pancreatic enzyme replacement therapy, steatorrhea, elderly patients
- MeSH terms
- Aged, Gastrointestinal Diseases, Humans, Evidence-Based Medicine, Proton Pump Inhibitors
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