Long-term Proton Pump Inhibitors Research Articles

Proton pump inhibitors and cardiovascular risk: a critical review.

Proton pump inhibitors (PPI) are widely used medications for gastrointestinal disorders. Recent research suggests a potential association between long-term PPI use and increased cardiovascular (CV) risk, creating a complex clinical dilemma. This review critically evaluates the current evidence for this association, considering the limitations of observational studies and the lack of definitive confirmation from randomized controlled trials.This review delves into the reported association between PPIs and adverse CV events, examining proposed mechanisms such as drug interactions, electrolyte imbalances induced by PPIs and their potential impact on cardiac and vascular function. Evidence suggests these mechanisms converge, with varying influence depending on patient populations.Clinicians require a risk-benefit analysis for each patient considering their CV risk profile. Alternative gastrointestinal therapies should be explored for high-bleeding risk patients. Medications with lower cytochrome-P450 interaction potential may be preferable among essential PPI users. Elucidating the specific mechanisms by which PPIs might influence CV health, assessing long-term vascular effects and investigating interactions with newer anticoagulant medications are crucial for future research.

8079 PPI Breaks a Leg! An Unusual Case of Atypical Femur Fracture

Abstract Disclosure: M. Sedghian: None. M. Flanagan: None. D. Pinkhasova: None. K. Selk: None. G. Moloney: None. Background: Atypical femur fractures (AFF) occur along the shaft of the femur extending from the subtrochanteric region proximally to the distal femoral metaphysis. These fractures have an increased incidence in patients taking bisphosphonates and denosumab for osteoporosis and develop as stress reactions in the lateral cortex of the femoral shaft (beaking). However, few cases that meet the characteristics of these fractures have occurred in patients who have never used antiresorptive drugs. We present a case with a history of long-term proton pump inhibitor (PPI) use and possible association with AFF. Clinical Case: The patient is a 68-year-old female with a past medical history of hypothyroidism who presented to the emergency department (ED) after an atraumatic femur fracture and consequently ground level fall. The patient reported experiencing a distinctive cracking sound in her femur while leaning over to wash her feet, resulting in a fall that prompted her to seek immediate care in the ED. Upon initial evaluation, radiographic imaging was significant for displaced left mid-femoral diaphyseal fracture and right femur lateral cortex thickening consistent with AFF. Labs were consistent with elevated PTH to 100.7 [18.4-80.1], Vit D2 1,25 (OH)2 <8 pg/mL, Vit D 25OH 34 ng/ml [30-100], and Calcium level of 9.5. Upon further history taking, the patient stated that she has been taking PPIs intermittently for more than 10 years. She denied a history of bisphosphonate and denosumab exposure, non-Hodgkin's lymphoma, rheumatoid arthritis, and COL1A2 variant mutations as main predisposing factors for atypical femur fractures. She had potential steroid exposure for less than a year before hospitalization as she was on "adrenal complex" from her functional medicine provider. The patient underwent open reduction and internal fixation of the left femur with placement of intramedullary nail and prophylactic fixation with placement of intramedullary nail of the right femur as there was radiographic evidence of beaking. Discussion/Conclusion: Several studies suggested a possible association between PPIs and fracture risk, especially hip fractures, but the relationship remains contentious. Overall, PPIs are positively associated with elevated fracture risk in multiple studies. Increased gastrin production and hypochlorhydria are the two main mechanisms that affect bone remodeling, decreasing bone turnover, impairing calcium absorption, and altering homocysteine levels through impairment of folate and vitamin B12 absorption.This case supports a potential association between long-term PPI use and atypical femur fractures. There have been other case reports that also highlight this potential risk of PPI use. This shows the importance of more comprehensive research on this topic as the number of patients on long-term PPIs is growing in outpatient settings. Presentation: 6/2/2024

S2327 Identifying High-Risk Profiles for Hypomagnesemia in Long-Term Proton Pump Inhibitor Users

S2327 Identifying High-Risk Profiles for Hypomagnesemia in Long-Term Proton Pump Inhibitor Users

Postoperative ileus in obstetric and gynecological practice: a prospective solution to the problem

Proton pump inhibitors (PPIs) are the undisputed leaders in the treatment of acid-related diseases. In actual clinical practice, the use of PPIs has been growing exponentially in recent decades. For a long time, PPIs were considered completely safe drugs for both short-term and long-term use. However, modern clinical guidelines and reviews and meta-analyses of the current decade on the safety of PPI use note that when prescribing PPIs in large doses for a long period, the possibility of developing numerous side effects should be taken into account. We searched the PubMed and Scopus information databases for publications on the safety of PPI use, including sources up to 12/01/2023. The review addresses issues of drug interactions between PPIs and chemotherapeutic drugs, which should certainly be taken into account in real clinical practice. In addition, recent reviews and meta-analyses have examined side effects of long-term PPI use, such as increased risk of infection (Clostridium difficile infection, community-acquired pneumonia), electrolyte disturbances, kidney damage, increased risk of hip, wrist and spine fractures; increased cardiovascular risk and a number of others, which can also have an adverse effect on the prognosis of cancer patients. The risk of developing gastric cancer with long-term PPI therapy can be considered as a likely side effect, since their association with PPI use is not denied or questioned in recent reviews and meta-analyses. There is still uncertainty regarding the increased risk of other cancers, since there are publications that do not confirm their association with PPI use. However, the presented review, despite a number of contradictions, allows us to conclude that the increased cancer risk with long-term use of PPIs is real and must be taken into account when prescribing PPIs for a long term.

Effects of Prolonged Proton-Pump Inhibitor Use on Renal Dysfunction and Bone Fragility: A Retrospective Study.

Proton-pump inhibitor (PPI) use for management of gastroesophageal reflux disease (GERD) consists of a short-duration trial, according to guidelines. Long-term usage is appropriate under certain indications. Literature has increasingly documented an adverse effect profile of PPIs, including kidney disease and bone fragility. To investigate the rate of occurrence of osteopenia, osteoporosis, and chronic kidney disease (CKD) in patients using PPI therapy for longer than the recommended trial period of 8 weeks. Retrospective cohort analysis of a single-site primary care clinic. Patients aged 18 to 65 years with PPI prescriptions longer than 8 weeks were included. Information regarding PPI prescriptions, demographics, and medical diagnoses was collected. The search discovered 293 PPI-users and 1908 never-PPI-users. Demographics varied, with a P-value <0.05 in age, body mass index (BMI), and black population (higher in PPI group). The PPI cohort featured higher rates of osteoporosis/osteopenia and CKD (P < 0.001). The odds ratios (ORs) of diagnosis with PPI use was 2.91 (95% CI = [1.692, 4.979]) in osteoporosis/osteopenia. The OR was 1.14 (95% CI = [1.141, 2.229]) in CKD and PPI use but higher with diabetes, elevated BMI, black race, and male gender. We observed increased occurrence rates of osteoporosis, or osteopenia, and CKD in patients with prolonged PPI use. Demographics varied in age, BMI, and black race proportion. A logistic regression revealed increased likelihood of kidney disease and osteoporosis/osteopenia in association with PPI use. These results add to the evidence regarding long-term PPI use and the development of these conditions, but additional studies are needed.

A review of proton pump inhibitor use in cystic fibrosis and considerations for deprescribing.

Use of proton-pump inhibitors (PPIs) is common among people with cystic fibrosis (pwCF) both for the management of suspected GERD, as well as pancreatic enzyme replacement therapy augmentation. Despite their use, limited data exist to demonstrate a clinically significant impact of PPIs on key endpoints in pwCF. Furthermore, the advent of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy may modify the need for use. These notions, coupled with the potential for adverse outcomes associated with long-term PPI use in pwCF, should facilitate re-evaluation of long-term PPI use in pwCF and promote potential deprescribing. Despite limited data on PPI deprescribing in pwCF, it intuitively mirrors the existing guidance in adults in the general population, but with added consideration given to tapering strategy, and monitoring for CF-specific outcomes such as nutritional and respiratory status. The development of a monitoring and re-initiation plan is key to reducing deprescribing inertia. This review aims to summarize the evidence that details the concern for long-term use of PPIs and provide CF clinicians with rationale and guidance on how to approach deprescribing in their practice.

Modern Management of Gastric Neuroendocrine Neoplasms.

Gastric neuroendocrine neoplasms (G-NENs) are a heterogeneous group of tumors that broadly fall into two groups. The first group, driven by oversecretion of gastrin, are generally multifocal, small, and behave indolently with a low (but non-zero) risk of progression and metastatic spread. They are conventionally categorized into type 1, with endogenous gastric-based overproduction of gastrin, and type 2 G-NEN, with overproduction of gastrin from an extra-gastric gastrin-secreting tumor. The second group, termed type 3 G-NEN, occur spontaneously and are potentially more aggressive, having a clinical course analogous to other neuroendocrine tumors of the gastrointestinal tract. Type 1 G-NEN can be managed with endoscopic surveillance and resection of visible lesions with great success, reserving surgery for the rare high-risk lesion, whereas surgical resection of the causative gastrin-secreting tumor in type 2 G-NEN is usually curative. Type 3 G-NEN is usually managed with formal surgical resection but there is growing evidence that limited surgery or even endoscopic resection in appropriately selected patients with low risk is both safe and effective. A novel subtype of G-NEN, associated with long-term proton pump inhibitor usage, is increasing in incidence. The pathophysiology seems to parallel type 1 G-NEN. In the setting of metastatic disease, which can occur in any subtype but is most common by far in type 3 G-NEN, the lack of trial data unique to G-NEN results in extrapolation of strategies and agents for treatment of non-gastric neuroendocrine disease. The rapid pace of development in this area is likely to benefit the metastatic G-NEN patient as well. As treatment is predicate on type of G-NEN, establishing the etiology of the lesion is crucial but growing knowledge of G-NEN pathophysiology and close collaboration between pathologists, gastroenterologists, radiologists, surgeons, and oncologists have enabled a growing trend towards de-escalation and less-invasive treatment paradigms.

Long-Term Proton Pump Inhibitor-Acid Suppressive Treatment Can Cause Vitamin B12 Deficiency in Zollinger-Ellison Syndrome (ZES) Patients.

Whether the long-term treatment of patients with proton pump inhibitors (PPIs) with different diseases [GERD, Zollinger-Ellison syndrome (ZES), etc.] can result in vitamin B12 (VB12) deficiency is controversial. In this study, in 175 patients undergoing long-term ZES treatment with anti-acid therapies, drug-induced control acid secretory rates were correlated with the presence/absence of VB12 deficiency, determined by assessing serum VB12 levels, measurements of VB12 body stores (blood methylmalonic acid (MMA) and total homocysteine[tHYC]), and other features of ZES. After a mean of 10.2 yrs. of any acid treatment (5.6 yrs. with PPIs), 21% had VB12 deficiency with significantly lower serum and body VB12 levels (p < 0.0001). The presence of VB12 deficiency did not correlate with any feature of ZES but was associated with a 12-fold lower acid control rate, a 2-fold higher acid control pH (6.4 vs. 3.7), and acid control secretory rates below those required for the activation of pepsin (pH > 3.5). Over a 5-yr period, the patients with VB12 deficiency had a higher rate of achlorhydria (73% vs. 24%) and a lower rate of normal acid secretion (0% vs. 49%). In conclusion, in ZES patients, chronic long-term PPI treatment results in marked acid hyposecretion, resulting in decreased serum VB12 levels and decreased VB12-body stores, which can result in VB12 deficiency.

Rational Use of Proton Pump Inhibitors among Patients Admitted in a Tertiary Care Hospital

Background: The prevalent usage of proton pump inhibitors (PPIs) is a testament to the effectiveness of this class of medications, but it also introduces risk associated with inappropriate prescriptive and consumptive practices. Because of the negative effect of incorrect usage and overdose of PPIs, it is very important for physicians to only prescribe these drugs when needed. However, recent studies showed some concerns about long-term PPIs consumption. The rational prescription of medications is vital to ensuring the optimal use of medical resources, providing effective therapy and minimizing adverse drug reactions. Methods: This observational study was conducted in the department of Pharmacology and therapeutics, Sylhet M.A.G. Osmani medical college, Sylhet, in collaboration with the department of Medicine, Surgery, Gastroenterology, Obstetrics and gynaecology, Sylhet M.A.G. Osmani medical college hospital, Sylhet, from July 2022 to June 2023. The sample size for this study was 600. Usage of PPIs was considered to be appropriate on the basis NICE guidelines and recommendations by Scarpignato et al. (2016) committees on behalf of three Italian scientific societies. Result: For 600 PPIs prescriptions, total 705 case sheets were reviewed. The mean age of the study patients was 42.94±17.16 years. Female were found more 359(59.8%) than male 241(40.2%). Out of 600 patients, based on the indications of PPI usage, 287 (47.8%) of prescriptions were found appropriate, whereas inappropriate prescriptions were found in 313 (52.2%) cases. Out of 287 patients who were prescribed PPIs in an appropriate indication, 175 (61%) patients were given PPIs in an appropriate dose, whereas inappropriate dose was found in 112 (39%) of patients. Again, among 175 patients who were prescribed PPIs for appropriate dose, 24 (13.7%) patients were given PPIs in an appropriate frequency, whereas inappropriate frequency was found in 151 (86.3%) of patients. Finally, 24/600 (4%) patients were prescribed in an appropriate indication with an appropriate dose and frequency, whereas inappropriate prescription were found in 576/600 (96%) patients. PPIs were used as prophylaxis for NSAIDs in highest number 147(51.2%) of patients. Oral was the most common 348(58%) route of prescribing PPIs. Omeprazole was the highest 577(96.2%) prescribed PPIs. Conclusion: Based on this study result, it could be concluded that in most of the patients PPIs prescriptions were not following appropriate indications, dose and frequency recommended by reference guidelines. Like any other drugs, PPIs should be prescribed for a clear indication, the minimum dose needed for the expected effect and medication halted when no longer necessary upon re-evaluation.

Overutilization of Proton Pump Inhibitors (PPIs) in a Community-Based Hospital: A QI Initiative

Introduction: Proton pump inhibitors (PPIs) are indicated for GERD, erosive esophagitis, and prophylactic use in patients at high risk for stress ulcerations. Long-term PPI therapy is associated with increased incidence of C. diff infections and community- and hospital-acquired pneumonia. Discontinuation of stress ulcer prophylaxis upon discharge and reevaluation of continued therapy will help reduce chronic, inappropriate treatment, which predisposes patients to adverse side effects. Aim: We sought to reform the process of inpatient PPI prescriptions based on clinical indications of therapy in order to reduce use and associated costs of PPIs by 30% over 6 months. Model for Improvement: We obtained an IRB exemption for a retrospective chart review study and collected pre-intervention data from 200 patients who had received PPI therapy between July-Aug 2022. Of these, 186 met inclusion criteria. We identified PPT overuse among all inpatient admissions, including those admitted under teaching services. Evaluating the timing of PPI initiation after admission, we found that a majority (83.8%) were started upon admission; 28.5% required PPIs throughout; and 25.2% of orders were placed within 1 day of discharge. The average duration of therapy was 3.9  2.59 days. On average, 50.5% of patients had a prior diagnosis of GERD, gastritis, or erosive esophagitis, justifying initiation of PPI therapy. However, almost a third (32.8%) met the criteria for stress ulcer prophylaxis. 17% of the cohort developed an adverse side effect, and almost 53% of patients were discharged with a new prescription for PPI. Measures: Root cause analysis revealed a lack of knowledge regarding adverse PPI effects leading to longer hospital stays. During the first PDSA, we conducted a session on “Use of PPI Inhibitors: Indications for Inpatient Prescriptions and Stress Ulcer Prophylaxis” in April 2023, educating Internal Medicine and Family Medicine resident teaching services about PPI therapy indications, contraindications, and adverse effects. Results: After our educational intervention, we collected and analyzed data from May 2023 to August 2023 and found 301 patients who met inclusion criteria. Their average age was 73.29 years. 169 patients (56%) had pre-existing diagnoses (GERD or erosive esophagitis), justifying initiation of Protonix. Of the remaining 132 without pre-existing conditions, 44 (35%) met criteria for starting stress ulcer prophylaxis. This was a 3% increase in appropriate utilization when compared to our pre-intervention data. 181 patients were discharged with a prescription for pantoprazole, of which 46 were PPI-naïve prior to admission. Conclusion: We found a decrease in inappropriate inpatient PPI administration by 3% after education. Although the post-intervention sample size was larger, the education resulted in a positive response in 1 month. The next PDSA cycle will alter the EMR order to provide only 3 orders for pantoprazole – one oral, one IV, and one for infusion, and orders will also require the selection of indication.

Physicians' perceptions and awareness of adverse effects of proton pump inhibitors and impact on prescribing patterns.

Background: Heightened scrutiny surrounds the inappropriate use of proton pump inhibitors (PPIs) due to concerns regarding potential serious adverse effects (AEs). Understanding the impact of these AEs on real-world practice is crucial. This study aimed to assess physicians' perceptions, experiences, awareness, and beliefs regarding published data on potential AEs associated with PPIs. Additionally, it sought to determine alterations in PPI prescribing patterns resulting from these AEs, explore attitudes towards PPI use, and ascertain recommendations for PPI use in clinical scenarios with varying levels of risk for upper gastrointestinal bleeding (UGIB). Method: A quantitative, cross-sectional study utilized a self-administered questionnaire, inviting 282 physicians from 55 primary healthcare centers and 334 internal medicine physicians from seven governmental hospitals to participate. Results: With a response rate of 87.8% (541/616), 74% (95% CI: 70.2-77.7) of respondents were somewhat or very familiar with published data on PPI AEs. Among the familiar, 69.5% (CI: 65.2-73.5) had somewhat or very much changed their PPI prescribing patterns. General concerns about AEs when prescribing PPIs were reported by 62% (CI: 56.7-65.1). Respondents displayed awareness of a median (IQR) of 15 (9) different AEs associated with long-term PPI use, including osteoporosis or osteopenia (90.2%), hypomagnesemia (81.5%), vitamin B12 deficiency (80.6%), and bone fracture (80.0%). Respondents believed that PPIs elevate the risk for a median (IQR) of 7 (6) different AEs, with osteoporosis or osteopenia (81.8%) being the most common, followed by hypomagnesemia (67.1%), and vitamin B12 deficiency (62.3%). The most common strategies for PPI de-escalation were PPI discontinuation (61%) and using PPI on-demand/as-needed (57.9%). The majority (87.4%) agreed or strongly agreed that PPI overuse is prevalent in Kuwait and 78.2% emphasized the necessity for large-scale education on rational PPI use for medical staff and the public. In the UGIB prevention scenarios, 43.6% recommended appropriately the PPI discontinuation in the minimal-risk scenario, while 56% recommended appropriately the PPI continuation in the high-risk scenario. Associations and comparative analyses revealed predictors influencing physicians' practices and attitudes toward PPI usage. Conclusion: These findings lay the foundation for future research and targeted interventions aimed at optimizing PPI prescribing practices and ensuring patient safety.

Association between Proton Pump Inhibitor Use and Risk of Incident Chronic Kidney Disease: Systematic Review and Meta-Analysis.

Proton pump inhibitors (PPIs) are among the most commonly prescribed medications. Recently, PPI use has been linked to the development of chronic kidney disease (CKD) and cardiovascular events. Our study aimed to investigate the relationship between PPI use and the incidence of chronic kidney disease using a systematic review and meta-analysis. We performed a comprehensive literature search in PubMed, Embase, and Cochrane databases from their inception until March 2024 for relevant studies. We compared outcomes between patients using PPIs, those not using PPIs, and those using histamine-2 receptor antagonists (H2RAs). Endpoints were pooled using the DerSimonian-and-Laird random-effects model as the hazard ratio (HR) with 95% confidence intervals (CIs). Our analysis included twelve studies with a total of 700,125 participants (286,488 on PPIs, 373,848 not on PPIs, and 39,789 on H2RAs), with follow-up periods ranging from three months to 14 years. The current meta-analysis revealed that PPI use is associated with a statistically significant increased risk of incident CKD (HR: 1.26, 95% CI: 1.16-1.38, p < 0.001) compared with non-users. Moreover, the risk of incident CKD is significantly higher in patients with PPI use compared to H2RA use (HR: 1.34, 95% CI: 1.13-1.59, p < 0.001). The results remained unchanged in terms of magnitude and direction after a leave-one-out analysis for both outcomes. Our multifaceted analysis showed that PPI use was associated with a higher incidence of CKD when compared to non-PPI use and H2RA use, respectively. These findings advocate for heightened vigilance and judicious use of long-term PPIs. Further large prospective longitudinal studies are warranted to validate these observations.

Endoscopic findings and outcomes of gastric mucosal changes relating to potassium-competitive acid blocker and proton pump inhibitor therapy.

Gastric mucosal changes associated with long-term potassium-competitive acid blocker and proton pump inhibitor (PPI) therapy may raise concern. In contrast to that for PPIs, the evidence concerning the safety of long-term potassium-competitive acid blocker use is scant. Vonoprazan (VPZ) is a representative potassium-competitive acid blocker released in Japan in 2015. In order to shed some comparative light regarding the outcomes of gastric mucosal lesions associated with a long-term acid blockade, we have reviewed six representative gastric mucosal lesions: fundic gland polyps, gastric hyperplastic polyps, multiple white and flat elevated lesions, cobblestone-like gastric mucosal changes, gastric black spots, and stardust gastric mucosal changes. For these mucosal lesions, we have evaluated the association with the type of acid blockade, patient gender, Helicobacter pylori infection status, the degree of gastric atrophy, and serum gastrin levels. There is no concrete evidence to support a significant relationship between VPZ/PPI use and the development of neuroendocrine tumors. Current data also shows that the risk of gastric mucosal changes is similar for long-term VPZ and PPI use. Serum hypergastrinemia is not correlated with the development of some gastric mucosal lesions. Therefore, serum gastrin level is unhelpful for risk estimation and for decision-making relating to the cessation of these drugs in routine clinical practice. Given the confounding potential neoplastic risk relating to H. pylori infection, this should be eradicated before VPZ/PPI therapy is commenced. The evidence to date does not support the cessation of clinically appropriate VPZ/PPI therapy solely because of the presence of these associated gastric mucosal lesions.

The association between proton-pump inhibitor use and recurrence of hepatocellular carcinoma after hepatectomy.

The association between long-term proton-pump inhibitors (PPIs) use and malignancies had long been discussed, but it still lacks consensus. Our study investigated the association between PPI use and hepatocellular carcinoma (HCC) recurrence following curative surgery. We retrospectively enrolled 6037 patients with HCC who underwent hepatectomy. Patients were divided into four groups according to their PPI usage. (non-users: <28 cumulative defined daily dose [cDDD]; short-term users: 28-89 cDDD; mid-term users: 90-179 cDDD, and long-term users: ≥180 cDDD, respectively). Recurrence-free survival (RFS) and overall survival (OS) were analyzed using Kaplan-Meier method and Cox proportional hazard models. Among the 6037 HCC patients, 2043 (33.84%) were PPI users. PPI users demonstrated better median RFS (3.10years, interquartile range [IQR] 1.49-5.01) compared with non-users (2.73years, IQR 1.20-4.74; with an adjusted hazard ratio [aHR] of 0.57, 95% confidence interval [CI] 0.44-0.74, P<0.001). When considering the cumulative dosage of PPI, only long-term PPI users had significant lower risk of HCC recurrence than non-PPI group (adj-HR: 0.50; 95% CI: 0.35-0.70; P<0.001). Moreover, the impact of long-term PPIs use on improving RFS was significant in most of the subgroup analysis, except in patients with advanced tumor stages, with non-cirrhosis, or with a history of chronic kidney disease. However, there were no significant differences in median OS between PPI users and non-users (4.23years, IQR 2.73-5.86 vs 4.04years, IQR 2.51-5.82, P=0.369). Long-term PPI use (≥180 cDDD) may be associated with a better RFS in HCC patients after hepatectomy.

Gastric Polyps in Long-Term Proton Pump Inhibitor Use: Identification of Risks and Characteristics.

Aim Estimate the prevalence of gastric polyps linked to long-term use of proton pump inhibitor (PPI), determine the various risk factors that promote this association, and identify the characteristics associated with these polyps. Methods This prospective cross-sectional study was conducted on approximately 1000 patients presenting to the Gastroenterology Endoscopic Department for upper GI endoscopy at two hospital centers in Beirut, Lebanon, over a period of 12 months from September 2021 to September 2022. The demographic and clinical data of patients who had been taking PPIs for at least one month were collected via a questionnaire. All patients with a previous Helicobacter pylori (H. pylori) infection, presence of hypergastrinemia, or a personal/family history of gastric polyps were excluded from this study. Statistical analyses were performed using SPSS 20 software. Categorical variables were compared by Fisher's exact test; p-values of less than 0.05 were considered statistically significant. Results The prevalence of gastric polyps linked to long-term PPI use was 30%. The minimum duration of daily PPI use required for the formation of polyps is around 24 months. The dosage did not play a significant role in increasing this prevalence. A significant correlation was found between chronic PPI use and factors such as sex, age range, duration, and type of PPI used. These polyps were predominantly found in females (with an OR of 2.9), increased with age, were mostly of the fundic gland type, and their size was proportionally linked to both the dosage and duration of daily PPI use. No cases of dysplasia within the fundic gland polyps (FGPs) were demonstrated in our study. Conclusion To date, there is no current data that prove an association between gastric cancer and PPI-induced FGPs. Additionally, the incidence of FGPs has increased with the widespread chronic use of PPIs. Therefore, attention should be drawn to the potential risk of dysplasia. Thus, the present study highlights the importance of limiting the prescription of PPIs to globally well-defined indications and determining the various risk factors that promote the association between gastric polyps and PPI use. This abstract was recently presented as an E-poster at the ESGE Days 2024 Congress on April 25-27, 2024, in Berlin, Germany.

Effect of long-term proton pump inhibitors on phosphocalcium metabolism and bone mineral density.

Aim: Although Proton pump inhibitors (PPIs) are well-tolerated, their long-term use may be associated with decreased bone mass. Methods: This is a case-control study including patients treated with PPIs (>1year) and control subjects who have not received PPIs treatment. Results: A total of 90 patients and 90 matched controls were included. PPIs use was associated with hypocalcemia and hypomagnesemia. Vitamin D3 deficiency and hyperparathyroidism were associated with PPIs use. Long-term PPIs use was significantly associated with decreased bone density. Risk factors of decreased bone mineral density (BMD) included age >50years, menopause, lack of sun exposure, double PPIs dose, daily intake, post-meal intake and association with a mucoprotective agent. Conclusion: Our results highlight the risk of decreased BMD in patients on long-term PPIs treatment.

Long-term proton pump inhibitors therapy and prevalence of hyperprolactinemia. a cross-sectional study in outpatient gastroenterology clinics

Objective: To evaluate serum prolactin and macroprolactin levels in patients on long-term proton pump inhibitors therapy. Method: The cross-sectional study was conducted from January 2018 to November 2019 after approval from the ethics review committee of the Commission on Science and Technology for Sustainable Development in the South University, Abbottabad, Pakistan. And comprised patients from two gastroenterology outpatient clinics in the Khyber Pakhtunkhwa province using proton pump inhibitors for &gt;3 months either alone or in combination with either histamine receptor antagonists or prokinetics. Blood samples were collected from each patient for hormonal screening. Data was analysed using SPSS 25. Results: Of the 166 patients, 101(60.8%) were females and 65(39.2%) were males. The overall mean age was 42.5±14.2 years, and the median serum prolactin level was 23.2ng/ml (interquartile range: 14.0-38.0ng/ml). There were 96(58%) patients with normoprolactinemia and 70(42%) with hypreprolactinemia. There were 19(11.4%) patients using combination therapy, while the rest were on proton pump inhibitors monotherapy. There was a significant increase in serum prolactin level with combination therapy compared to monotherapy (p=0.001). Pateints having treatment duration 11-20 months (p=0.006) and &gt;40 months (p=0.001) were at high risk of developing hyperprolactinemia. Conclusion: Long-term use of proton pump inhibitors could increase serum prolactin levels, and appropriate evaluation is essential for clinical management. Key Words: Proton pump inhibitors, Long-term therapy, Hyperprolactinemia, Omeprazole, Prolactin.

Rebound Acid Hypersecretion after Withdrawal of Long-Term Proton Pump Inhibitor (PPI) Treatment-Are PPIs Addictive?

Proton pump inhibitors (PPIs) are widely used in the long-term treatment of gastroesophageal reflux disease (GERD) and other upper gastrointestinal disorders, such as the healing of peptic ulcers and/or prophylactic treatment of peptic ulcers. PPIs are also widely used as symptomatic treatment in patients with functional dyspepsia. One of the adverse effects of the long-term use of PPI is rebound acid hypersecretion (RAHS), which can occur after the withdrawal of PPI therapy due to a compensatory increase in gastric acid production. Mechanisms of the RAHS have been well established. Studies have shown that pentagastrin-stimulated acid secretion after the discontinuation of PPIs increased significantly compared to that before treatment. In healthy volunteers treated with PPIs, the latter induced gastrointestinal symptoms in 40-50% of subjects after the discontinuation of PPI therapy but after stopping the placebo. It is important for practicing physicians to be aware and understand the underlying mechanisms and inform patients about potential RAHS before discontinuing PPIs in order to avoid continuing unnecessary PPI therapy. This is important because RAHS may lead patients to reuptake PPIs as symptoms are incorrectly thought to originate from the recurrence of underlying conditions, such as GERD. Mechanisms of RAHS have been well established; however, clinical implications and the risk factors for RAHS are not fully understood. Further research is needed to facilitate appropriate management of RAHS in the future.

Inappropriate Use of Proton Pump Inhibitor Among Elderly Patients in British Columbia: What are the Long-term Adverse Events?

Proton pump inhibitors (PPIs) are one of the most used classes of drugs. For most indications, PPIs are only recommended up to 8 weeks duration. However, PPI use continues to expand. Regular and prolonged use of PPIs should be avoided because of the risk of adverse events. The main objective of this study was to (1) investigate the extent of PPI usage in people aged 65 or older in the province of British Columbia (BC), Canada, (2) provide an overview of the harms associated with the long-term use of PPIs. We examined utilization trends of the PPIs in BC since the year 2009 using PharmaNet, BC's medication dispensing database where the information is accessible to community pharmacists. We performed a comprehensive literature search for relevant reviews reporting harms associated with long-term use of PPIs. A search was conducted from January 2014 to June 2022. Between 2000 and 2018 BC's population grew by 20%, but the use of PPIs escalated to 257%. Of these older British Columbians, 62% had a cumulative exposure exceeding 2 years and 42% exceeded 5 years. This is alarming because the recommended treatment duration is 4-12 weeks for common indications including reflux esophagitis, and duodenal and gastric ulcers. Only 13.5% were dispensed PPIs for 90 days or less. Patients on long-term PPI therapy should be reassessed. Adverse events of PPI use are common among older adults. We identified over 217 systematic reviews published during the last 8 years of specific harms associated with long-term daily usage of PPIs. These harms include increased risks of death, cardiovascular disease, acute renal injury, chronic kidney disease, dementia, fractures, hypomagnesemia, iron deficiency, vitamin B12 deficiency, enteric infection (including C. difficile), pneumonia, and neoplasia (gastric cancer, carcinoids, and colon cancer), and drug interactions. This study revealed a high prevalence of PPI use among elderly populations in BC, Canada. The overutilization of PPIs is often a result of failure to re-evaluate the need for continuation of therapy. Published studies identified signals of serious harm from long-term PPI exposure. Healthcare providers with patients can reverse the relentless expansion of long-term PPI exposure by discussing the expected benefits and potential harms.

E060 A multinational survey investigating the unmet needs and patient perspectives concerning proton pump inhibitors in systemic sclerosis

Abstract Background/Aims The gastrointestinal (GI) tract is largely (&amp;gt;95%) affected in systemic sclerosis (SSc) and its involvement is associated with significant morbidity, mortality and huge impact on the quality of life. Upper GI tract dysfunction, often presenting with gastroesophageal reflux disease (GERD) is one of the principal complaints. Proton pump inhibitors (PPIs) are widely used to treat GERD in SSc. However, not all patients respond to this therapy, and many remain on long-term treatment. Significant concerns about PPI long-term safety have been raised. Our aim was to identify perspectives and unmet needs of SSc patients on PPIs. Methods An online English survey, targeting SSc patients on PPIs was developed and distributed through social media and international patient associations. The survey was launched on 4th November 2022 and kept open for 4 weeks. Results 301 respondents from 14 countries completed the survey (UK 19.3% and US 70.4%). Most respondents were between 30-70 years and the majority were female (95%). The most frequently reported symptoms were acid reflux (97%), dysphagia (60%), and trouble swallowing or food got stuck in the chest (32%). Multiple PPIs use (two: 30% and three: 21%; in series) was common and the majority (89%) reported improvement in GI symptoms with PPIs. Even though only 19% experienced side effects on PPIs, most respondents (79%) were concerned (Table 1). Half (47%) experienced a flare of symptoms after initial improvement with PPIs and 58% received lifestyle information, while most (85%) searched online for information about PPIs. A minority (12%) reported that a surgical approach was discussed, and 46% indicated that they would be willing to undergo surgery, despite having significant concerns. Conclusion Our survey highlights the importance of upper GI symptoms in SSc patients and the frequent use of PPIs. There is significant heterogeneity in use, and treatment is often not fully effective. Patients have concerns about side effects related to long-term PPI use. There is a clear unmet need regarding patients’ education about PPIs. A surgical approach is rarely discussed, although patients would potentially consider this approach. Further research is needed to optimize the therapeutic strategy concerning PPIs in SSc. Disclosure G. Bandini: None. A. Alunno: None. F. Oliveira Pinheiro: None. C. Campochiaro: None. I. Galetti: None. P. Matucci Cerinic: None. B. Ruaro: None. K. El Aoufy: None. M. Melis: None. A. Moggi Pignone: None. L. Dagna: None. M. Matucci Cerinic: None. Z. McMahan: None. M. Hughes: None.