AGA Clinical Practice Update on De-Prescribing of Proton Pump Inhibitors: Expert Review
2022; Elsevier BV; Volume: 162; Issue: 4 Linguagem: Inglês
10.1053/j.gastro.2021.12.247
ISSN1528-0012
AutoresLaura E. Targownik, Deborah A. Fisher, Sameer D. Saini,
Tópico(s)Helicobacter pylori-related gastroenterology studies
ResumoDescriptionProton pump inhibitors (PPIs) are among the most commonly used medications in the world. Developed for the treatment and prevention of acid-mediated upper gastrointestinal conditions, these agents are being used increasingly for indications where their benefits are less certain. PPI overprescription imposes an economic cost and contributes to polypharmacy. In addition, PPI use has been increasingly linked to a number of adverse events (PPI-associated adverse events [PAAEs]). Therefore, de-prescribing of PPIs is an important strategy to lower pill burden while reducing real costs and theoretical risks. The purpose of this clinical update was to provide Best Practice Advice (BPA) statements about how to approach PPI de-prescribing in ambulatory patients.MethodsOur guiding principle was that, although PPIs are generally safe, patients should not use any medication when there is not a reasonable expectation of benefit based on scientific evidence or prior treatment response. Prescribers are responsible for determining whether PPI use is absolutely or conditionally indicated and, when uncertainty exists, to incorporate patient perspectives into PPI decision making. We collaboratively outlined a high-level “process map” of the conceptual approach to de-prescribing PPIs in a clinical setting. We identified the following 3 key domains that required BPA guidance: documentation of PPI indication; identifying suitable candidates for consideration of de-prescribing; and optimizing successful de-prescribing. Co-authors drafted 1 or more potential BPAs, supported by literature review, for each domain. All co-authors reviewed, edited, and selected or rejected draft BPAs for inclusion in the final list submitted to the American Gastroenterological Association Governing Board. Because this was not a systematic review, we did not carry out a formal rating of the quality of evidence or strength of the presented considerations.Best Practice Advice StatementsBest Practice Advice 1All patients taking a PPI should have a regular review of the ongoing indications for use and documentation of that indication. This review should be the responsibility of the patient’s primary care provider.Best Practice Advice 2All patients without a definitive indication for chronic PPI should be considered for trial of de-prescribing.Best Practice Advice 3Most patients with an indication for chronic PPI use who take twice-daily dosing should be considered for step down to once-daily PPI.Best Practice Advice 4Patients with complicated gastroesophageal reflux disease, such as those with a history of severe erosive esophagitis, esophageal ulcer, or peptic stricture, should generally not be considered for PPI discontinuation.Best Practice Advice 5Patients with known Barrett’s esophagus, eosinophilic esophagitis, or idiopathic pulmonary fibrosis should generally not be considered for a trial of de-prescribing.Best Practice Advice 6PPI users should be assessed for upper gastrointestinal bleeding risk using an evidence-based strategy before de-prescribing.Best Practice Advice 7Patients at high risk for upper gastrointestinal bleeding should not be considered for PPI de-prescribing.Best Practice Advice 8Patients who discontinue long-term PPI therapy should be advised that they may develop transient upper gastrointestinal symptoms due to rebound acid hypersecretion.Best Practice Advice 9When de-prescribing PPIs, either dose tapering or abrupt discontinuation can be considered.Best Practice Advice 10The decision to discontinue PPIs should be based solely on the lack of an indication for PPI use, and not because of concern for PAAEs. The presence of a PAAE or a history of a PAAE in a current PPI user is not an independent indication for PPI withdrawal. Similarly, the presence of underlying risk factors for the development of an adverse event associated with PPI use should also not be an independent indication for PPI withdrawal. Proton pump inhibitors (PPIs) are among the most commonly used medications in the world. Developed for the treatment and prevention of acid-mediated upper gastrointestinal conditions, these agents are being used increasingly for indications where their benefits are less certain. PPI overprescription imposes an economic cost and contributes to polypharmacy. In addition, PPI use has been increasingly linked to a number of adverse events (PPI-associated adverse events [PAAEs]). Therefore, de-prescribing of PPIs is an important strategy to lower pill burden while reducing real costs and theoretical risks. The purpose of this clinical update was to provide Best Practice Advice (BPA) statements about how to approach PPI de-prescribing in ambulatory patients. Our guiding principle was that, although PPIs are generally safe, patients should not use any medication when there is not a reasonable expectation of benefit based on scientific evidence or prior treatment response. Prescribers are responsible for determining whether PPI use is absolutely or conditionally indicated and, when uncertainty exists, to incorporate patient perspectives into PPI decision making. We collaboratively outlined a high-level “process map” of the conceptual approach to de-prescribing PPIs in a clinical setting. We identified the following 3 key domains that required BPA guidance: documentation of PPI indication; identifying suitable candidates for consideration of de-prescribing; and optimizing successful de-prescribing. Co-authors drafted 1 or more potential BPAs, supported by literature review, for each domain. All co-authors reviewed, edited, and selected or rejected draft BPAs for inclusion in the final list submitted to the American Gastroenterological Association Governing Board. Because this was not a systematic review, we did not carry out a formal rating of the quality of evidence or strength of the presented considerations. Best Practice Advice Statements All patients taking a PPI should have a regular review of the ongoing indications for use and documentation of that indication. This review should be the responsibility of the patient’s primary care provider. All patients without a definitive indication for chronic PPI should be considered for trial of de-prescribing. Most patients with an indication for chronic PPI use who take twice-daily dosing should be considered for step down to once-daily PPI. Patients with complicated gastroesophageal reflux disease, such as those with a history of severe erosive esophagitis, esophageal ulcer, or peptic stricture, should generally not be considered for PPI discontinuation. Patients with known Barrett’s esophagus, eosinophilic esophagitis, or idiopathic pulmonary fibrosis should generally not be considered for a trial of de-prescribing. PPI users should be assessed for upper gastrointestinal bleeding risk using an evidence-based strategy before de-prescribing. Patients at high risk for upper gastrointestinal bleeding should not be considered for PPI de-prescribing. Patients who discontinue long-term PPI therapy should be advised that they may develop transient upper gastrointestinal symptoms due to rebound acid hypersecretion. When de-prescribing PPIs, either dose tapering or abrupt discontinuation can be considered. The decision to discontinue PPIs should be based solely on the lack of an indication for PPI use, and not because of concern for PAAEs. The presence of a PAAE or a history of a PAAE in a current PPI user is not an independent indication for PPI withdrawal. Similarly, the presence of underlying risk factors for the development of an adverse event associated with PPI use should also not be an independent indication for PPI withdrawal. Proton pump inhibitors (PPIs) are among the most commonly used medications in the United States, if not the world. Observational studies have demonstrated that PPI use has increased over time and that 7%–15% of patients use these medications at any time, with the prevalence increasing to 40% for patients 70 years or older.1Pottegard A. Broe A. Hallas J. et al.Use of proton-pump inhibitors among adults: a Danish nationwide drug utilization study.Therap Adv Gastroenterol. 2016; 9: 671-678Google Scholar, 2Daniels B. Pearson S.A. Buckley N.A. et al.Long-term use of proton-pump inhibitors: whole-of-population patterns in Australia 2013-2016.Therap Adv Gastroenterol. 2020; 131756284820913743Google Scholar, 3Bustillos H. Leer K. Kitten A. et al.A cross-sectional study of national outpatient gastric acid suppressant prescribing in the United States between 2009 and 2015.PLoS One. 2018; 13e0208461Google Scholar, 4Lassalle M. Le Tri T. Bardou M. et al.Use of proton pump inhibitors in adults in France: a nationwide drug utilization study.Eur J Clin Pharmacol. 2020; 76: 449-457Google Scholar Approximately one-quarter of all patients who receive a PPI will continue to use them for at least 1 year.5Othman F. Card T.R. Crooks C.J. Proton pump inhibitor prescribing patterns in the UK: a primary care database study.Pharmacoepidemiol Drug Saf. 2016; 25: 1079-1087Google Scholar Although PPIs are the treatment of choice for the management of acid-mediated upper gastrointestinal (GI) conditions, such as erosive esophagitis and peptic ulcer disease,6Chiba N. De Gara C.J. Wilkinson J.M. et al.Speed of healing and symptom relief in grade II to IV gastroesophageal reflux disease: a meta-analysis.Gastroenterology. 1997; 112: 1798-1810Google Scholar, 7Yeomans N.D. Tulassay Z. Juhasz L. et al.A comparison of omeprazole with ranitidine for ulcers associated with nonsteroidal antiinflammatory drugs. Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID-associated Ulcer Treatment (ASTRONAUT) Study Group.N Engl J Med. 1998; 338: 719-726Google Scholar, 8Hawkey C.J. Karrasch J.A. Szczepanski L. et al.Omeprazole compared with misoprostol for ulcers associated with nonsteroidal antiinflammatory drugs. Omeprazole versus Misoprostol for NSAID-induced Ulcer Management (OMNIUM) Study Group.N Engl J Med. 1998; 338: 727-734Google Scholar, 9Walan A. Bader J.P. Classen M. et al.Effect of omeprazole and ranitidine on ulcer healing and relapse rates in patients with benign gastric ulcer.N Engl J Med. 1989; 320: 69-75Google Scholar these agents are being used increasingly for less clear indications and for indeterminate durations. In a large observational study examining ambulatory visits of PPI users, nearly two-thirds had no clear indication for PPI use.10Rotman S.R. Bishop T.F. Proton pump inhibitor use in the U.S. ambulatory setting, 2002-2009.PLoS One. 2013; 8e56060Google Scholar In this context, multiple national gastroenterology organizations have called for limiting PPI use.11American Gastroenterological Association. Five things physicians and patients should question. Choosing Wisely.https://www.choosingwisely.org/wp-content/uploads/2015/02/AGA-Choosing-Wisely-List.pdfGoogle Scholar, 12American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults.J Am Geriatr Soc. 2015; 63: 2227-2246Google Scholar, 13Gastroenterology. Eleven things physicians and patients should question. Choosing Wisely Canada. Canadian Association of Gastroenterology, Canadian IBD Network for Research and Growth in Quality Improvement, Crohn’s and Colitis Canada.https://choosingwiselycanada.org/gastroenterology/Google Scholar In addition, PPIs have been available over-the-counter in the United States since 2003; therefore, physicians may not be involved in a patient’s decision to initiate therapy.14Sheikh I. Waghray A. Waghray N. et al.Consumer use of over-the-counter proton pump inhibitors in patients with gastroesophageal reflux disease.Am J Gastroenterol. 2014; 109: 789-794Google Scholar As PPI use has become more common, the emerging literature has identified several adverse effects potentially linked to these drugs,15Elias E. Targownik L.E. The clinician's guide to proton pump inhibitor related adverse events.Drugs. 2019; 79: 715-731Google Scholar,16Vaezi M.F. Yang Y.X. Howden C.W. Complications of proton pump inhibitor therapy.Gastroenterology. 2017; 153: 35-48Google Scholar from chronic kidney disease to fracture to dementia and, most recently, COVID-19.17Targownik L.E. Lix L.M. Metge C.J. et al.Use of proton pump inhibitors and risk of osteoporosis-related fractures.CMAJ. 2008; 179: 319-326Google Scholar, 18Gomm W. von Holt K. Thome F. et al.Association of proton pump inhibitors with risk of dementia: a pharmacoepidemiological claims data analysis.JAMA Neurol. 2016; 73: 410-416Google Scholar, 19Xie Y. Bowe B. Li T. et al.Risk of death among users of proton pump inhibitors: a longitudinal observational cohort study of United States veterans.BMJ Open. 2017; 7e015735Google Scholar, 20Klatte D.C.F. Gasparini A. Xu H. et al.Association between proton pump inhibitor use and risk of progression of chronic kidney disease.Gastroenterology. 2017; 153: 702-710Google Scholar, 21Almario C.V. Chey W.D. Spiegel B.M.R. Increased risk of COVID-19 among users of proton pump inhibitors.Am J Gastroenterol. 2020; 115: 1707-1715Google Scholar All studies to date reporting these specific associations have been observational and therefore cannot establish causality.22Ma C. Shaheen A.A. Congly S.E. et al.Interpreting reported risks associated with use of proton pump inhibitors: residual confounding in a 10-year analysis of national ambulatory data.Gastroenterology. 2020; 158: 780-782.e3Google Scholar In contrast, randomized controlled trials (RCTs) comparing PPIs with placebo have not shown a higher rate of any adverse event among PPI users.23Moayyedi P. Eikelboom J.W. Bosch J. et al.Safety of proton pump inhibitors based on a large, multi-year, randomized trial of patients receiving rivaroxaban or aspirin.Gastroenterology. 2019; 157: 682-691.e2Google Scholar Nonetheless, this body of literature has raised concerns among prescribers and patients about the long-term safety of PPIs. This concern may promote inappropriate discontinuation of PPIs when a strong indication for use exists.24Chan F.K. Wong V.W. Suen B.Y. et al.Combination of a cyclo-oxygenase-2 inhibitor and a proton-pump inhibitor for prevention of recurrent ulcer bleeding in patients at very high risk: a double-blind, randomised trial.Lancet. 2007; 369: 1621-1626Google Scholar In this context, we developed a set of Best Practice Advice (BPA) statements about how to approach PPI de-prescribing—“the clinically supervised process of stopping or reducing the dose of medications when they cause harm or no longer provide benefit”—in ambulatory patients.25Linsky A. Gellad W.F. Linder J.A. et al.Advancing the science of deprescribing: a novel comprehensive conceptual framework.J Am Geriatr Soc. 2019; 67: 2018-2022Google Scholar Best Practice Advice 1: All patients taking a PPI should have a regular review of the ongoing indications for use and documentation of that indication. This review should be the responsibility of the patient’s primary care provider (PCP). To determine whether a PPI’s potential benefits outweigh the potential harms, it is essential to know why the PPI was prescribed and the indications for continuing use. Without an ongoing indication or evidence of benefit for the prescribing indication, the PPI can only incur harm. These harms include pill burden, medication-related costs, and potential adverse effects related to long-term use. Therefore, clinicians should clearly document an acceptable indication for the drug and that the indication is ongoing. In the absence of an appropriate ongoing indication, the medication should be considered for de-prescribing. Currently, most PPIs are prescribed by PCPs.26Abrahami D. McDonald E.G. Schnitzer M. et al.Trends in acid suppressant drug prescriptions in primary care in the UK: a population-based cross-sectional study.BMJ Open. 2020; 10e041529Google Scholar Although gastroenterologists may be consulted, they do not generally provide long-term follow-up for patients using PPIs for common indications (eg, uncomplicated gastroesophageal reflux disease [GERD] and dyspepsia). PCPs are also likely the first physician point of contact for patients using over-the-counter PPIs. Therefore, we suggest that the PCP should be primarily responsible for reviewing the presence of ongoing indications for PPI use, and identifying candidates for de-prescribing. When a gastroenterologist is involved in the patient’s care, we encourage documentation, as applicable, of indications for prolonged PPI use and clinical end points that signify PPI discontinuation. In health care settings with the infrastructure to review medication use, misuse, or overuse more broadly, a pharmacist- or nurse-specialist–centered multidisciplinary approach may facilitate systematic identification of inappropriate PPI use and de-prescribing.27Farrell B. Conklin J. Dolovich L. et al.Deprescribing guidelines: an international symposium on development, implementation, research and health professional education.Res Social Adm Pharm. 2019; 15: 780-789Google Scholar Best Practice Advice 2: All patients without a definitive indication for chronic PPI should be considered for trial of de-prescribing. Definite and conditional indications for long-term and short-term PPI use are shown in Table 1. Multiple studies have found that patients often take PPIs in the absence of a continuing indication.28Ladd A.M. Panagopoulos G. Cohen J. et al.Potential costs of inappropriate use of proton pump inhibitors.Am J Med Sci. 2014; 347: 446-451Google Scholar, 29Heidelbaugh J.J. Kim A.H. Chang R. et al.Overutilization of proton-pump inhibitors: what the clinician needs to know.Therap Adv Gastroenterol. 2012; 5: 219-232Google Scholar, 30Heidelbaugh J.J. Goldberg K.L. Inadomi J.M. Magnitude and economic effect of overuse of antisecretory therapy in the ambulatory care setting.Am J Manag Care. 2010; 16: e228-e234Google Scholar, 31Glew C.M. Rentler R.J. Use of proton pump inhibitors and other acid suppressive medications in newly admitted nursing facility patients.J Am Med Dir Assoc. 2007; 8: 607-609Google Scholar The vast majority of trials demonstrating efficacy have tested durations of 4–12 weeks,32Sigterman K.E. van Pinxteren B. Bonis P.A. et al.Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease.Cochrane Database Syst Rev. 2013; 5: CD002095Google Scholar or no more than 6–12 months for maintenance therapy.33Donnellan C. Sharma N. Preston C. et al.Medical treatments for the maintenance therapy of reflux oesophagitis and endoscopic negative reflux disease.Cochrane Database Syst Rev. 2005; CD003245Google Scholar Chronic PPI use may be unintended. For example, a PPI initiated in the hospital for an acute indication (eg, stress ulcer prophylaxis) may be continued at discharge without the review of indication and ongoing need suggested in BPA 1.34Blackett J.W. Faye A.S. Phipps M. et al.Prevalence and risk factors for inappropriate continuation of proton pump inhibitors after discharge from the intensive care unit.Mayo Clin Proc. 2021; 96: 2550-2560Google Scholar In addition, PPIs are frequently initiated without a definite indication, notably for empiric treatment of laryngopharyngeal symptoms of cough, throat clearing, globus, and voice hoarseness. Because an RCT has definitively demonstrated that PPIs have no benefit in the empiric management of these symptoms,35O’Hara J. Stocken D.D. Watson G.C. et al.Use of proton pump inhibitors to treat persistent throat symptoms: multicentre, double blind, randomised, placebo controlled trial.BMJ. 2021; 372m4903Google Scholar these patients should be considered for de-prescribing.Table 1Indications for Proton Pump Inhibitor UseIndicationsDefinitely indicated for long-term use (>8 wk)Conditionally indicated for long-term useNot indicated for long-term useDefinitely indicated for acute/short-term use (≤8 wk)Conditionally indicated for acute/short-term useNot indicated for acute/short-term useBarrett’s esophagusClinically significant (LA Classification grade C/D) erosive esophagitisEsophageal strictures from GERD (ie, peptic strictures)Zollinger-Ellison syndromeEosinophilic esophagitisGastroprotection in users of ASA/nonsteroidal anti-inflammatory drug at high risk for GI bleedingPrevention of progression of idiopathic pulmonary fibrosisPPI-responsive endoscopy-negative reflux disease, with recurrence on PPI cessationPPI-responsive functional dyspepsia, with recurrence on PPI cessationPPI-responsive upper airway symptoms ascribed to laryngopharyngeal reflux, with recurrence on PPI cessationRefractory steatorrhea in chronic pancreatic insufficiency with enzyme replacementSecondary prevention of gastric and duodenal peptic ulcers with no concomitant antiplatelet drugsSymptoms of nonerosive reflux disease with no sustained response to high-dose PPI therapyFunctional dyspepsia with no sustained response to PPI therapySteroid therapy in the absence of ASA/nonsteroidal anti-inflammatory drug therapyPrevention of recurrent upper GI bleeding from causes other than:Peptic ulcer disease, including gastric and duodenal erosionsErosive esophagitisHelicobacter pylori eradicationStress ulcer prophylaxis for ICU patients with risk factorsUninvestigated GERD/dyspepsiaTreatment of NSAID-related gastric and duodenal peptic ulcersInitial or on-demand treatment of endoscopy-negative reflux diseaseInitial treatment of functional dyspepsiaUninvestigated dyspepsiaUlcer prevention after sclerotherapy or band ligation treatment of esophageal varicesPrevention of rebleeding from Mallory-Weiss tearsEmpiric treatment of laryngopharyngeal symptomatologyAcute undifferentiated abdominal painAcute nausea and vomiting not believed to be related to GERD/esophagitisAny isolated lower GI symptomatologyASA, aspirin; ICU, intensive care unit; LA, Los Angeles. Open table in a new tab ASA, aspirin; ICU, intensive care unit; LA, Los Angeles. Best Practice Advice 3: Most patients with an indication for chronic PPI use who take twice-daily dosing should be considered for step down to once-daily PPI. Double-dose PPIs (standard dose twice daily or a double-strength dose once daily) have not been studied in any RCT and are not US Food and Drug Administration–approved. Nonetheless, up to 15% of PPI users are on a higher-than-standard dose.36Targownik L.E. Metge C. Roos L. et al.The prevalence of and the clinical and demographic characteristics associated with high-intensity proton pump inhibitor use.Am J Gastroenterol. 2007; 102: 942-950Google Scholar Higher-dose PPIs increase the costs of care and have been more strongly associated with certain complications, including community-acquired pneumonia, hip fracture, and Clostridium difficile infection; although there is no direct evidence of a causal relationship between PPI use and these adverse events.37Dial S. Delaney J.A. Barkun A.N. et al.Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile-associated disease.JAMA. 2005; 294: 2989-2995Google Scholar, 38Laheij R.J. Sturkenboom M.C. Hassing R.J. et al.Risk of community-acquired pneumonia and use of gastric acid-suppressive drugs.JAMA. 2004; 292 (1955–1560)Google Scholar, 39Yang Y.X. Lewis J.D. Epstein S. et al.Long-term proton pump inhibitor therapy and risk of hip fracture.JAMA. 2006; 296: 2947-2953Google Scholar There is evidence to support the use of higher doses of oral PPIs over standard dosing in the acute setting to prevent rebleeding from peptic ulcer disease.40Chen C.C. Lee J.Y. Fang Y.J. et al.Randomised clinical trial: high-dose vs. standard-dose proton pump inhibitors for the prevention of recurrent haemorrhage after combined endoscopic haemostasis of bleeding peptic ulcers.Aliment Pharmacol Ther. 2012; 35: 894-903Google Scholar However, there is minimal evidence to support their use for the maintenance of healed esophagitis or prevention of complications of peptic ulcer disease. High-dose PPIs are often recommended in patients with suspected laryngopharyngeal reflux or Barrett’s esophagus.41Shaheen N.J. Falk G.W. Iyer P.G. et al.ACG Clinical Guideline: diagnosis and management of Barrett's esophagus.Am J Gastroenterol. 2016; 111 (quiz 51): 30-50Google Scholar,42Kahrilas P.J. Shaheen N.J. Vaezi M.F. et al.American Gastroenterological Association Medical Position Statement on the management of gastroesophageal reflux disease.Gastroenterology. 2008; 135 (1391.e1–e5): 1383-1391Google Scholar No study of Barrett’s esophagus specifically demonstrates that double-dose PPIs are superior to standard-dose PPIs to prevent extension or progression to dysplasia or cancer. In addition, PPIs at any dose are ineffective in managing laryngopharyngeal symptoms.35O’Hara J. Stocken D.D. Watson G.C. et al.Use of proton pump inhibitors to treat persistent throat symptoms: multicentre, double blind, randomised, placebo controlled trial.BMJ. 2021; 372m4903Google Scholar High-dose PPIs are indicated for Zollinger-Ellison syndrome, which is exceedingly rare (1/1,000,000).43Metz D.C. Comer G.M. Soffer E. et al.Three-year oral pantoprazole administration is effective for patients with Zollinger-Ellison syndrome and other hypersecretory conditions.Aliment Pharmacol Ther. 2006; 23: 437-444Google Scholar,44Metz D.C. Sostek M.B. Ruszniewski P. et al.Effects of esomeprazole on acid output in patients with Zollinger-Ellison syndrome or idiopathic gastric acid hypersecretion.Am J Gastroenterol. 2007; 102: 2648-2654Google Scholar Therefore, most high-dose PPI users should be considered for stepping down to standard dosing. In a trial of 117 patients using higher-than-standard doses of PPIs for GERD, 80% successfully stepped down to standard doses of PPI without significant recurrence of symptoms or the need to again increase the PPI dose.45Inadomi J.M. McIntyre L. Bernard L. et al.Step-down from multiple- to single-dose proton pump inhibitors (PPIs): a prospective study of patients with heartburn or acid regurgitation completely relieved with PPIs.Am J Gastroenterol. 2003; 98: 1940-1944Google Scholar Therefore, PPI dose de-escalation for GERD can be effective for the majority of users. It is unknown whether this success rate for de-escalation can be duplicated across other indications. Best Practice Advice 4: Patients with complicated GERD, such as those with a history of severe erosive esophagitis, esophageal ulcer, or peptic stricture, should generally not be considered for PPI discontinuation. Most patients with GERD have nonerosive disease.46El-Serag H.B. Epidemiology of non-erosive reflux disease.Digestion. 2008; 78: 6-10Google Scholar However, approximately 20% of patients with untreated GERD have erosive esophagitis.47Zagari R.M. Fuccio L. Wallander M.A. et al.Gastro-oesophageal reflux symptoms, oesophagitis and Barrett's oesophagus in the general population: the Loiano-Monghidoro study.Gut. 2008; 57: 1354-1359Google Scholar Erosive esophagitis can lead to GERD-related complications, such as GI bleeding or stricture formation. PPIs have been shown to be effective in healing erosive esophagitis and in preventing the development and recurrence of complications of GERD in long-term users.48Carlsson R. Galmiche J.-P. Dent J. et al.Prognostic factors influencing relapse of oesophagitis during maintenance therapy with antisecretory drugs: a meta-analysis of long-term omeprazole trials.Aliment Pharmacol Ther. 1997; 11: 473-482Google Scholar A history of erosive esophagitis is also more common among persons who are found to have Barrett’s esophagus.49Hanna S. Rastogi A. Weston A.P. et al.Detection of Barrett's esophagus after endoscopic healing of erosive esophagitis.Am J Gastroenterol. 2006; 101: 1416-1420Google Scholar In addition, recurrence of esophagitis is common after withdrawal of treatment, particularly in those with more clinically significant disease (eg, symptomatic Los Angeles Classification grade C or D).50Vakil N.B. Shaker R. Johnson D.A. et al.The new proton pump inhibitor esomeprazole is effective as a maintenance therapy in GERD patients with healed erosive oesophagitis: a 6-month, randomized, double-blind, placebo-controlled study of efficacy and safety.Aliment Pharmacol Ther. 2001; 15: 927-935Google Scholar Therefore, in patients with a known history of more severe erosive esophagitis (Los Angeles Classification grade C/D) or those with GERD-related complications, PPIs should generally not be considered for discontinuation unless the benefits and harms have been weighed and discussed with the patient. Because many patients with GERD are treated empirically, and even severe erosive esophagitis generally heals with PPI use without long-term sequelae, it may not be known whether a PPI user has had severe erosive esophagitis, or has a predisposition to developing more severe erosive esophagitis in the absence of ongoing PPI use. In these patients, de-prescribing can be considered, but PPI use should be quickly re-initiated in those who develop symptoms or signs suggestive of the emergence of complicated GERD, with consideration of upper endoscopy to confirm the presence of severe erosive esophagitis. Best Practice Advice 5: Patients with known Barrett’s esophagus, eosinophilic esophagitis, or idiopathic pulmonary fibrosis should generally not be considered for a trial of de-prescribing. There are several conditions in which a trial of de-prescribing has the potential to cause greater harm than benefit and should therefore not be pursued. First, one key long-term complication of GERD is esophageal adenocarcinoma.51Lagergren J. Bergström R. Lindgren A. et al.Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma.N Engl J Med. 1999; 340: 825-831Google Scholar In patients with its known precursor lesion, Barrett’s
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