{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T15:47:37Z","timestamp":1794584857569,"version":"4.9.1"},"reference-count":98,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,31]],"date-time":"2025-08-31T00:00:00Z","timestamp":1756598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Proton pump inhibitors (PPIs) are among the most prescribed drugs worldwide owing to their proven efficacy in symptom control and mucosal healing for acid-related disorders including gastroesophageal reflux disease (GORD), peptic ulcer disease, Helicobacter pylori eradication, functional dyspepsia, and gastroprotection in high-risk patients. However, long-term use beyond approved indications is increasingly common and has raised safety concerns. Observational studies link chronic PPI use to a myriad of adverse outcomes such as enteric infections (e.g., Clostridioides difficile), nutrient deficiencies (magnesium, vitamin B12), osteoporotic fractures, chronic kidney disease, dementia, and gastric and colorectal cancer. While causality is not always established, these associations warrant cautious risk\u2013benefit assessment in patients receiving prolonged therapy. Current guidelines advocate periodic review of ongoing PPI use and emphasise deprescribing where appropriate. Strategies include dose reduction, on-demand or intermittent use, and switching to H2-receptor antagonists, particularly in patients with non-erosive reflux disease or functional dyspepsia. Tools from the National Institute for Health and Clinical Excellence, American College of Gastroenterology, and the Canadian Deprescribing Network assist clinicians in identifying candidates for tapering or discontinuation. This narrative review focuses on the concept of \u201cPPI stewardship\u201d by providing an evidence-based overview of PPI indications, risks, and deprescribing strategies to promote appropriate, safer, and patient-centred use of acid-suppressive therapy.<\/jats:p>","DOI":"10.3390\/medicina61091569","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T08:28:15Z","timestamp":1756715295000},"page":"1569","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Proton Pump Inhibitors (PPIs)\u2014An Evidence-Based Review of Indications, Efficacy, Harms, and Deprescribing"],"prefix":"10.3390","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9527-1685","authenticated-orcid":false,"given":"Monica","family":"Andrawes","sequence":"first","affiliation":[{"name":"Royal Cornwall Hospital NHS Trust, Truro TR1 3LJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wessam","family":"Andrawes","sequence":"additional","affiliation":[{"name":"Royal Cornwall Hospital NHS Trust, Truro TR1 3LJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4836-7971","authenticated-orcid":false,"given":"Abhishek","family":"Das","sequence":"additional","affiliation":[{"name":"Royal Cornwall Hospital NHS Trust, Truro TR1 3LJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1273-9561","authenticated-orcid":false,"given":"Keith","family":"Siau","sequence":"additional","affiliation":[{"name":"Royal Cornwall Hospital NHS Trust, Truro TR1 3LJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Scarpignato, C., Gatta, L., Zullo, A., Blandizzi, C., SIF-AIGO-FIMMG Group, Italian Society of Pharmacology, The Italian Association of Hospital Gastroenterologists, and The Italian Federation of General Practitioners (2016). Effective and safe proton pump inhibitor therapy in acid-related diseases\u2014A position paper addressing benefits and potential harms of acid suppression. BMC Med., 14.","DOI":"10.1186\/s12916-016-0718-z"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1053\/j.gastro.2017.01.031","article-title":"The risks and benefits of long-term use of proton pump inhibitors: Expert review and best practice advice from the American gastroenterological association","volume":"152","author":"Freedberg","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_3","unstructured":"(2014). NICE Clinical Guideline CG184. Gastro-oesophageal Reflux Disease and Dyspepsia in Adults: Investigation and Management, National Institute for Health and Care Excellence (UK)."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1111\/j.1365-2036.2006.02798.x","article-title":"Review article: The role of acid suppression in patients with non-erosive reflux disease or functional heartburn","volume":"23","author":"DeVault","year":"2006","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1136\/bmj.39406.449456.BE","article-title":"Overprescribing proton pump inhibitors","volume":"336","author":"Forgacs","year":"2008","journal-title":"BMJ"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e041529","DOI":"10.1136\/bmjopen-2020-041529","article-title":"Trends in acid suppressant drug prescriptions in primary care in the UK: A population-based cross-sectional study","volume":"10","author":"Abrahami","year":"2020","journal-title":"BMJ Open"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1002\/pds.5676","article-title":"Trends in use of proton pump inhibitors among adults in the United States from 1999 to 2018","volume":"32","author":"Bergin","year":"2023","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Torres-Bondia, F., de Batlle, J., Galv\u00e1n, L., Buti, M., Barb\u00e9, F., and Pi\u00f1ol-Ripoll, G. (2022). Evolution of the consumption trend of proton pump inhibitors in the Lleida Health Region between 2002 and 2015. BMC Public Health, 22.","DOI":"10.1186\/s12889-022-13217-6"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e072793","DOI":"10.1136\/bmjopen-2023-072793","article-title":"Evolution of proton pump inhibitor prescribing from 2017 to 2021 at 14 secondary and tertiary hospitals in China: A multicentre cross-sectional study","volume":"13","author":"Zeng","year":"2023","journal-title":"BMJ Open"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Yamamichi, N., Shimamoto, T., Takahashi, Y., Takahashi, M., Takeuchi, C., Wada, R., Fujishiro, M., and Zarnegar, R. (2022). Trends in proton pump inhibitor use, reflux esophagitis, and various upper gastrointestinal symptoms from 2010 to 2019 in Japan. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0270252"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"BJGPO.2024.0059","DOI":"10.3399\/BJGPO.2024.0059","article-title":"Prescribing practices for proton pump inhibitors among primary care physicians in England: An evaluation","volume":"9","author":"Plehhova","year":"2025","journal-title":"BJGP Open"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"21","DOI":"10.3961\/jpmph.24.357","article-title":"Utilization of acid suppressants after withdrawal of ranitidine in Korea: An interrupted time series analysis","volume":"58","author":"Choi","year":"2025","journal-title":"J. Prev. Med. Public Health"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1007\/s12664-023-01428-7","article-title":"Guidelines on optimizing the use of proton pump inhibitors: PPI stewardship","volume":"42","author":"Dutta","year":"2023","journal-title":"Indian J. Gastroenterol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e5","DOI":"10.1136\/gutjnl-2024-332154","article-title":"Inappropriate use of proton pump inhibitors in clinical practice globally: A systematic review and meta-analysis","volume":"74","author":"Dutta","year":"2024","journal-title":"Gut"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1002\/pds.4043","article-title":"Proton pump inhibitor prescribing patterns in the UK: A primary care database study","volume":"25","author":"Othman","year":"2016","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"ref_16","unstructured":"U.S. Food and Drug Administration (2025, August 20). Drug Safety and Availability, Available online: https:\/\/www.fda.gov\/drugs\/drug-safety-and-availability."},{"key":"ref_17","unstructured":"(2025, August 20). Homepage. European Medicines Agency (EMA). Available online: https:\/\/www.ema.europa.eu."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"By the 2019 American Geriatrics Society Beers Criteria\u00ae Update Expert Panel (2019). American Geriatrics Society 2019 updated AGS Beers Criteria\u00ae for Potentially Inappropriate Medication Use in Older Adults. J. Am. Geriatr. Soc., 67, 674\u2013694.","DOI":"10.1111\/jgs.15767"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1093\/ageing\/afu145","article-title":"STOPP\/START criteria for potentially inap-propriate prescribing in older people: Version 2","volume":"44","author":"Omahony","year":"2015","journal-title":"Age Ageing"},{"key":"ref_20","unstructured":"(2025, August 20). Choosing Wisely: An initiative of the ABIM Foundation. Available online: https:\/\/www.choosingwisely.org."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"27","DOI":"10.14309\/ajg.0000000000001538","article-title":"ACG clinical guideline for the diagnosis and management of gastroesophageal reflux disease","volume":"117","author":"Katz","year":"2022","journal-title":"Am. J. Gastroenterol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1053\/j.gastro.2021.12.247","article-title":"AGA Clinical Practice Update on De-Prescribing of Proton Pump Inhibitors: Expert Review Targownik","volume":"162","author":"Targownik","year":"2022","journal-title":"Gastroenterology"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Peyton-Navarrete, A., Nguyen, M.H.C., and FakhriRavari, A. (2025). Prescribing responsibly: Navigating the Tides of deprescribing in proton pump inhibitor stewardship. Pharmacoepidemiology, 4.","DOI":"10.20944\/preprints202506.0438.v1"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1186\/s13063-016-1267-7","article-title":"TOPPITS: Trial Of Proton Pump Inhibitors in Throat Symptoms. Study protocol for a randomised controlled trial","volume":"17","author":"Watson","year":"2016","journal-title":"Trials"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1136\/bmj.38232.680567.EB","article-title":"The effectiveness of five strategies for the prevention of gastrointestinal toxicity induced by non-steroidal anti-inflammatory drugs: Systematic review","volume":"329","author":"Hooper","year":"2004","journal-title":"BMJ"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1053\/j.gastro.2014.06.007","article-title":"Risk of Upper Gastrointestinal Bleeding From Different Drug Combinations","volume":"147","author":"Masclee","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/j.1365-2036.2007.03541.x","article-title":"Meta-analysis: Gastrointestinal bleeding due to interaction between selective serotonin uptake inhibitors and non-steroidal anti-inflammatory drugs","volume":"27","author":"Loke","year":"2008","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_28","first-page":"728","article-title":"Practice Parameters Committee of the American College of Gastroenterolo-gy.Guidelines for prevention of NSAID-related ulcer complications","volume":"104","author":"Lanza","year":"2009","journal-title":"Am. J. Gastroenterol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e123","DOI":"10.1161\/CIR.0000000000000404","article-title":"2016 ACC\/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: A report of the American college of cardiology\/American heart association task force on clinical practice guidelines: An update of the 2011 ACCF\/AHA\/SCAI guideline for percutaneous coronary intervention, 2011 ACCF\/AHA guideline for coronary artery bypass graft surgery, 2012 ACC\/AHA\/ACP\/AATS\/PCNA\/SCAI\/STS guideline for the diagnosis and management of patients with stable ischemic heart disease, 2013 ACCF\/AHA guideline for the management of ST-elevation myocardial infarction, 2014 AHA\/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes, and 2014 ACC\/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery","volume":"134","author":"Levine","year":"2016","journal-title":"Circulation"},{"key":"ref_30","first-page":"447","article-title":"2020 international consensus on the management of antithrombotic therapy in patients at risk of gastrointestinal bleeding","volume":"172","author":"Abraham","year":"2020","journal-title":"Ann. Intern. Med."},{"key":"ref_31","first-page":"625","article-title":"Position paper of the Italian Society of Cardiology and AIGO on gastro-protection in patients on antiplatelet therapy","volume":"20","author":"Caterina","year":"2019","journal-title":"G. Ital. Cardiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1093\/eurheartj\/ehx393","article-title":"2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation","volume":"39","author":"Ibanez","year":"2018","journal-title":"Eur Heart J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"375","DOI":"10.4330\/wjc.v15.i8.375","article-title":"Proton pump inhibitors and gastroprotection in patients treated with antithrombotic drugs: A cardiologic point of view","volume":"15","author":"Abrignani","year":"2023","journal-title":"World J. Cardiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"a1","DOI":"10.1055\/s-0034-1393172","article-title":"Diagnosis and management of nonvariceal upper gastrointestinal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline","volume":"47","author":"Gralnek","year":"2015","journal-title":"Endoscopy"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1136\/gutjnl-2016-312288","article-title":"Management of Helicobacter pylori infection\u2014The Maastricht V\/Florence consensus report","volume":"66","author":"Malfertheiner","year":"2017","journal-title":"Gut"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1001\/jama.2018.17242","article-title":"Association of oral anticoagulants and proton pump inhibitor cotherapy with hospitalization for upper gastrointestinal tract bleeding","volume":"320","author":"Ray","year":"2018","journal-title":"JAMA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4676","DOI":"10.1111\/bcp.15478","article-title":"Protective effect of proton-pump inhibitor against gastrointestinal bleeding in patients receiving oral anticoagulants: A systematic review and meta-analysis","volume":"88","author":"Ahn","year":"2022","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1093\/europace\/euab065","article-title":"2021 European heart rhythm association practical guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation","volume":"23","author":"Steffel","year":"2021","journal-title":"Europace"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4693","DOI":"10.1182\/bloodadvances.2020001830","article-title":"American Society of Hematology 2020 Guidelines for Management of Venous Thromboembolism: Treatment of Deep Vein Thrombosis and Pulmonary Embolism","volume":"4","author":"Ortel","year":"2020","journal-title":"Blood Adv."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1053\/j.gastro.2015.05.002","article-title":"Prevention of Dabigatran-Related Gastrointestinal Bleeding with Gastroprotective Agents: A Population-Based Study","volume":"149","author":"Chan","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_41","unstructured":"Lanas, A., and Ferrandez, A. (2013). Inappropriate prevention of NSAID-induced gastrointestinal events among long-term users in the UK primary care setting. Gastroenterol. Res. Pract."},{"key":"ref_42","first-page":"3","article-title":"Review article: The geographic differences in NSAID-induced ulcer rates--does it matter","volume":"13","author":"Schoenfeld","year":"1999","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"101","DOI":"10.7326\/0003-4819-152-2-201001190-00009","article-title":"for the International Consensus Upper Gastrointestinal Bleeding Conference Group* International Consensus Recommendations on the Management of Patients With Nonvariceal Upper Gastrointestinal Bleeding","volume":"152","author":"Barkun","year":"2010","journal-title":"Ann. Intern. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"805","DOI":"10.7326\/M19-1795","article-title":"Management of Nonvariceal Upper Gastrointestinal Bleeding: Guideline Recommendations from the International Consensus Group","volume":"171","author":"Barkun","year":"2019","journal-title":"Ann. Intern. Med."},{"key":"ref_45","unstructured":"(2022). NICE Guideline NG226. Osteoarthritis in Over 16s: Diagnosis and Management, NICE."},{"key":"ref_46","unstructured":"NICE (2025, August 20). Rheumatoid Arthritis in Adults: Management. Available online: https:\/\/www.nice.org.uk\/guidance\/ng100."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1136\/annrheumdis-2016-210715","article-title":"EULAR recommendations for the management of rheumatoid arthritis with synthetic and bio-logical disease-modifying antirheumatic drugs: 2016 update","volume":"76","author":"Yousefi","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e004587","DOI":"10.1136\/bmjopen-2013-004587","article-title":"Corticosteroids and risk of gastrointestinal bleeding: A systematic review and meta-analysis","volume":"4","author":"Narum","year":"2014","journal-title":"BMJ Open"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4067","DOI":"10.3748\/wjg.v11.i26.4067","article-title":"Head-to-head comparison of H2-receptor antagonists and proton pump inhibitors in the treatment of erosive esophagitis: A meta-analysis","volume":"11","author":"Wang","year":"2005","journal-title":"World J. Gastroenterol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"17562848241241224","DOI":"10.1177\/17562848241241223","article-title":"P-CAB versus PPI in the eradication of Helicobacter pylori: A systematic review and network meta-analysis","volume":"17","author":"Jiang","year":"2024","journal-title":"Therap. Adv. Gastroenterol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.lfs.2018.12.058","article-title":"Proton pump inhibitors therapy and risk of bone diseases: An update meta-analysis","volume":"218","author":"Liu","year":"2019","journal-title":"Life Sci."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Wu, C.-C., Liao, M.-H., Kung, W.-M., and Wang, Y.-C. (2023). Proton pump inhibitors and risk of chronic kidney disease: Evidence from observational studies. J. Clin. Med., 12.","DOI":"10.3390\/jcm12062262"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1001\/jamainternmed.2015.7193","article-title":"Proton pump inhibitor use and the risk of chronic kidney disease","volume":"176","author":"Lazarus","year":"2016","journal-title":"JAMA Intern. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"106488","DOI":"10.1016\/j.jinf.2025.106488","article-title":"Proton pump inhibitors and the risk of Clostridioides difficile infection: A systematic review and dose-response meta-analysis","volume":"90","author":"Finke","year":"2025","journal-title":"J. Infect."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.3109\/0886022X.2015.1057800","article-title":"Proton pump inhibitors linked to hypomagnesemia: A systematic review and meta-analysis of observational studies","volume":"37","author":"Cheungpasitporn","year":"2015","journal-title":"Ren. Fail."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Lambert, A.A., Lam, J.O., Paik, J.J., Ugarte-Gil, C., Drummond, M.B., and Crowell, T.A. (2015). Risk of community-acquired pneumonia with outpatient proton-pump inhibitor therapy: A systematic review and meta-analysis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0128004"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2435","DOI":"10.1001\/jama.2013.280490","article-title":"Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency","volume":"310","author":"Lam","year":"2013","journal-title":"JAMA"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.1007\/s10620-011-1589-y","article-title":"Association between proton pump inhibitor use and anemia: A retrospective cohort study","volume":"56","author":"Sarzynski","year":"2011","journal-title":"Dig. Dis. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1001\/archinternmed.2010.89","article-title":"Iatrogenic gastric acid suppression and the risk of nosocomial Clostridium difficile infection","volume":"170","author":"Howell","year":"2010","journal-title":"Arch. Intern. Med."},{"key":"ref_60","first-page":"e87383","article-title":"Proton pump inhibitor use and risk of Clostridioides difficile infection: An umbrella review of 11 meta-analyses","volume":"17","author":"Nalabothula","year":"2025","journal-title":"Cureus"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1007\/s00296-013-2709-0","article-title":"Bone density in proton pump inhibitors users: A prospective study","volume":"33","author":"Ozdil","year":"2013","journal-title":"Rheumatol. Int."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1001\/archinternmed.2010.94","article-title":"Proton pump inhibitor use, hip fracture, and change in bone mineral density in postmenopausal women: Results from the Women\u2019s Health Initiative","volume":"170","author":"Gray","year":"2010","journal-title":"Arch. Intern. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1053\/j.gastro.2017.04.047","article-title":"Complications of proton pump inhibitor therapy","volume":"153","author":"Vaezi","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1038\/ajg.2012.200","article-title":"The relationship between proton pump inhibitor use and longitudinal change in bone mineral density: A population-based study [corrected] from the Canadian Multicentre Osteoporosis Study (CaMos)","volume":"107","author":"Targownik","year":"2012","journal-title":"Am. J. Gastroenterol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/ajg.2016.481","article-title":"Long-term proton pump inhibitor use is not associated with changes in bone strength and structure","volume":"112","author":"Targownik","year":"2017","journal-title":"Am. J. Gastroenterol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1136\/gutjnl-2015-310376","article-title":"Proton pump inhibitors affect the gut microbiome","volume":"65","author":"Imhann","year":"2016","journal-title":"Gut"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1111\/jgh.14040","article-title":"Oral microbiome alterations of healthy volunteers with proton pump inhibitor","volume":"33","author":"Mishiro","year":"2018","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s00535-017-1371-9","article-title":"Meta-analysis: Proton pump inhibitors moderately increase the risk of small intestinal bacterial overgrowth","volume":"53","author":"Su","year":"2018","journal-title":"J. Gastroenterol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.cgh.2012.12.011","article-title":"Proton pump inhibitor use and the risk of small intestinal bacterial overgrowth: A meta-analysis","volume":"11","author":"Lo","year":"2013","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1053\/j.gastro.2023.05.052","article-title":"Association of proton pump inhibitor use with incident dementia and cognitive decline in older adults: A prospective cohort study","volume":"165","author":"Mehta","year":"2023","journal-title":"Gastroenterology"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Xie, K., Li, J., Tang, C., Huang, Z., and Chen, M. (2024). Association between proton pump inhibitors and dementia risk: A Mendelian randomization study. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-79821-1"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1001\/jamaneurol.2015.4791","article-title":"Association of proton pump inhibitors with risk of dementia","volume":"73","author":"Gomm","year":"2016","journal-title":"JAMA Neurol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e14422","DOI":"10.1097\/MD.0000000000014422","article-title":"Proton pump inhibitor use and risk of dementia: Systematic review and meta-analysis","volume":"98","author":"Li","year":"2019","journal-title":"Medicine"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1136\/gutjnl-2017-314605","article-title":"Long-term proton pump inhibitors and risk of gastric cancer development after treatment for Helicobacter pylori: A population-based study","volume":"67","author":"Cheung","year":"2018","journal-title":"Gut"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1056\/NEJMoa1007964","article-title":"Clopidogrel with or without omeprazole in coronary artery disease","volume":"363","author":"Bhatt","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1111\/joim.12698","article-title":"Long-term use of proton pump inhibitors, dose\u2013response relationship and associated risk of ischemic stroke and myocardial infarction","volume":"283","author":"Sehested","year":"2018","journal-title":"J. Intern. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/s13019-024-03161-4","article-title":"Risk of stroke associated with proton pump inhibitor use among individuals with and without pre-existing cardiovascular diseases: A systematic review and meta-analysis","volume":"20","author":"Shabil","year":"2025","journal-title":"J. Cardiothorac. Surg."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Rossi, A., Perrella, L., Scotti, S., Olmastroni, E., Galimberti, F., Ardoino, I., Orlando, V., Menditto, E., Franchi, C., and Casula, M. (2024). Approaches to deprescribing proton pump inhibitors in clinical practice: A systematic review. J. Clin. Med., 13.","DOI":"10.3390\/jcm13206283"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1177\/87551225231166531","article-title":"Vonoprazan: A new potassium-competitive acid blocker","volume":"39","author":"Onge","year":"2023","journal-title":"J. Pharm. Technol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"334","DOI":"10.5056\/jnm18029","article-title":"Potent potassium-competitive acid blockers: A New Era for the treatment of acid-related diseases","volume":"24","author":"Oshima","year":"2018","journal-title":"J. Neurogastroenterol. Motil."},{"key":"ref_81","first-page":"354","article-title":"Deprescribing proton pump inhibitors: Evidence-based clinical practice guideline","volume":"63","author":"Farrell","year":"2017","journal-title":"Can. Fam. Physician"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.pharmthera.2016.08.001","article-title":"Potassium-competitive acid blockers: Advanced therapeutic option for acid-related diseases","volume":"168","author":"Inatomi","year":"2016","journal-title":"Pharmacol. Ther."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/apt.17510","article-title":"A translational pharmacokinetic\/pharmacodynamic approach supports optimal vonoprazan dosing for erosive oesophagitis and Helicobacter pylori infection","volume":"58","author":"Scarpignato","year":"2023","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_84","first-page":"65","article-title":"Treatment and chemoprevention of NSAID-associated gastrointestinal complications","volume":"5","author":"Frech","year":"2009","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_85","unstructured":"Kudaravalli, P., Patel, P., and John, S. (2025). Sucralfate. StatPearls, StatPearls Publishing."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e27923","DOI":"10.1097\/MD.0000000000027923","article-title":"The efficacy and safety of different bismuth agents in Helicobacter pylori first-line eradication: A multicenter, randomized, controlled clinical trial","volume":"100","author":"Cao","year":"2021","journal-title":"Medicine"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e19520","DOI":"10.1097\/MD.0000000000019520","article-title":"Efficacy of vonoprazan for initial and maintenance therapy in reflux esophagitis, nonerosive esophagitis, and proton pump inhibitor-resistant gastroesophageal reflux disease","volume":"99","author":"Gotoh","year":"2020","journal-title":"Medicine"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Dong, Y., Xu, H., Zhang, Z., Zhou, Z., and Zhang, Q. (2023). Comparative efficiency and safety of potassium competitive acid blockers versus Lansoprazole in peptic ulcer: A systematic review and meta-analysis. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1304552"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"4811","DOI":"10.3748\/wjg.v18.i35.4811","article-title":"Quality of ulcer healing in gastrointestinal tract: Its pathophysiology and clinical relevance","volume":"18","author":"Arakawa","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/s40264-014-0144-0","article-title":"Pharmacokinetic drug interaction profiles of proton pump inhibitors: An update","volume":"37","author":"Wedemeyer","year":"2014","journal-title":"Drug Saf."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1053\/j.gastro.2009.03.058","article-title":"Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy","volume":"137","author":"Reimer","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Alonso, N., Zappia, C.D., Cabrera, M., Davio, C.A., Shayo, C., Monczor, F., and Fern\u00e3\u00a1Ndez, N.C. (2015). Physiological implications of biased signaling at histamine H2 receptors. Front. pharmacology, 6.","DOI":"10.3389\/fphar.2015.00045"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1007\/s00464-014-3431-z","article-title":"EAES recommendations for the management of gastroesophageal reflux disease","volume":"28","author":"Fuchs","year":"2014","journal-title":"Surg. Endosc."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/S0140-6736(16)32404-7","article-title":"Peptic ulcer disease","volume":"390","author":"Lanas","year":"2017","journal-title":"Lancet"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/S0140-6736(09)61246-0","article-title":"Famotidine for the prevention of peptic ulcers and oe-sophagitis in patients taking low-dose aspirin (FAMOUS): A phase III, randomised, double-blind, placebo-controlled trial","volume":"374","author":"Taha","year":"2009","journal-title":"Lancet"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Scarpignato, C., Lanas, A., Blandizzi, C., Lems, W.F., Hermann, M., and Hunt, R.H. (2015). Safe prescribing of non-steroidal anti-inflammatory drugs in patients with osteoarthritis--an expert consensus addressing benefits as well as gastrointestinal and cardiovascular risks. BMC Med., 13.","DOI":"10.1186\/s12916-015-0285-8"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1038\/s41395-018-0132-6","article-title":"Correction: ACG Clinical Guideline: Treatment of Helicobacter pylori Infection","volume":"113","author":"Chey","year":"2018","journal-title":"Am. J. Gastroenterol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.japh.2019.08.012","article-title":"Successful deprescribing of unnecessary proton pump inhibitors in a primary care clinic","volume":"60","author":"Odenthal","year":"2020","journal-title":"J. Am. Pharm. Assoc. 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