Proton Pump Inhibitor Therapy In Patients Research Articles

Proton-Pump Inhibitor Therapy in Patients with Erosive Esophagitis: A Real-World Scenario

Background: Gastroesophageal reflux disease (GERD) has three classical phenotypes, namely erosive esophagitis (EE), nonerosive reflux disease, and Barrett’s esophagus. Patients with GERD are managed with lifestyle changes, dietary interventions, and proton-pump inhibitors (PPI). Aim: To determine the patterns of PPI use in patients with documented EE. Methods: This prospective study recruited all patients with symptoms of GERD (heartburn and/or regurgitation with or without chest pain) and documented significant reflux esophagitis (Los Angeles grading LA-B or beyond on endoscopy). Lifestyle and dietary changes were initiated and all patients were prescribed twice daily PPI for 8 weeks. PPI was tapered as the requirement beyond 8 weeks. Follow-up was done at weeks 8, 12, and 24. The outcomes analysed included number of patients where complete PPI withdrawal was possible at week 24 and determinants of continued PPI use at 24 weeks of therapy. Statistical analysis was performed using Chi-square test, Mann–Whitney U-test, sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio. P < 0.05 was considered statistically significant. Results: The study cohort included 53 patients-42 with reflux esophagitis LA-B and 11 with reflux esophagitis LA-C (median age 46 years [22–77 years]; 28 [52.3%] males). There was significant difference in consumption pattern of PPI between week 12 and 24 (P = 0.008). At week 12, 15.1% were off PPI and 67% required intermittent dosing. At week 24, 45.3% of cases were off PPI therapy and 43.4% required intermittent dosing. Only 11.3% patients continued drug use at once a day dosing. Lower body mass index (BMI) (P 0.01) and age (P 0.01) were linked with complete PPI withdrawal at week 24. Conclusion: The present study highlights that PPI withdrawal is possible in 15.1% and 45.3% cases with EE after week 12 and week 24 of therapy, respectively. Lower BMI and age are likely to be associated with PPI withdrawal at week 24.

Optimal Wireless Reflux Monitoring Metrics to Predict Discontinuation of Proton Pump Inhibitor Therapy.

Ambulatory reflux monitoring performed off proton pump inhibitor (PPI) is the gold standard diagnostic test for nonerosive gastroesophageal reflux disease (GERD). However, the diagnostic metrics and optimal duration of monitoring are not well defined. This study evaluated the performance of multiple metrics across distinct durations of wireless reflux monitoring off PPI against the ability to discontinue PPI therapy in patients with suboptimal PPI response. This single-arm clinical trial performed over 4 years at 2 centers enrolled adults with troublesome GERD symptoms and inadequate response to > 8 weeks of PPI. Participants underwent 96-hour wireless pH monitoring off PPI. Primary outcome was whether the subject successfully discontinued PPI or resumed PPI within 3 weeks. Of 132 participants, 30% discontinued PPI. Among multiple metrics assessed, total acid exposure time (AET) of 4.0% performed best in predicting PPI discontinuation (odds ratio 2.9 [95% confidence interval 1.4, 6.4]; P = 0.006), with other thresholds of AET and DeMeester score performing comparably. AET was significantly higher on day 1 of monitoring compared with other days, and prognostic performance significantly declined when only assessing the first 48 hours of monitoring (area under the curve for 96 hours 0.63 vs area under the curve for 48 hours 0.57; P = 0.01). This clinical trial highlights the AET threshold of 4.0% as a high-performing prognostic marker of PPI discontinuation. 96 hours of monitoring performed better than 48 hours, in predicting ability to discontinue PPI. These data can inform current diagnostic approaches for patients with GERD symptoms who are unresponsive to PPI therapy.

Comparison in Adherence to Treatment between Patients with Mild-Moderate and Severe Reflux Esophagitis: A Prospective Study.

Purpose: Gastro-esophageal reflux disease (GERD) is prevalent and causes erosive esophagitis (EE) with varying degrees of severity (A to D according to the Los Angeles Classification). Adherence to medical therapy is crucial for treatment success. We compared adherence to treatment recommendations between patients with EE grades C/D and A/B. Methods: A follow-up study was conducted during 2019–2020 among GERD patients who underwent a diagnostic gastroscopy 1–4 years earlier. Telephone interviews were conducted with patients diagnosed with severe EE grades C/D (n = 99) and randomly selected patients with mild–moderate EE grades A/B (n = 50). Patients with grades A/B were classified as adherent if they took proton pump inhibitors (PPIs) for 2–3 months as recommended. Patients with grades C/D were classified as adherent if they took medications for a prolonged period (>6 months) and performed a follow-up endoscopy as recommended. Results: The mean age of the participants was 44.6 years (SD = 15.1). The mean duration of PPIs therapy in patients with EE grades A/B was 9.4 months (SD = 8.7). Fourteen (14.2%) patients with EE grades A/B were non-adherent to treatment, compared to 21 (40.8%) patients with EE grades of C/D: adjusted OR = 0.06; CI 95% 0.02–0.18, p < 0.001. Follow-up endoscopy was performed by 44% of EE–C/D patients. Unmarried patients compared to married ones were less adherent (adjusted OR = 0.23; 95% CI 0.08–0.69, p < 0.001). Conclusions: Patients with esophagitis (EE–A/B) were more adherent to medical therapy when compared to patients with more severe esophagitis (EE–C/D).

24-Hour Multichannel Intraluminal Impedance-pH in Proton Pump Inhibitor Nonresponders vs Responders in Patients With Laryngopharyngeal Reflux.

This study aimed to evaluate the characteristics of reflux in proton pump inhibitor (PPI) nonresponders vs responders in patients with laryngopharyngeal reflux (LPR) by using 24-hour multichannel intraluminal impedance-pH (MII-pH) monitoring. Prospective cohort study. A tertiary care otolaryngology clinic. Patients with typical LPR symptoms showing >1 proximal reflux episode were considered to have LPR and investigated prospectively. Patients were prescribed high-dose PPI twice daily and followed up for at least 2 months. Patients with LPR showing a ≥50% decrease in the follow-up reflux symptom index score during treatment periods as compared with pretreatment were defined as responders; others were defined as nonresponders. Various parameters in 24-hour MII-pH monitoring between nonresponders and responders with LPR were compared with Student's t test and receiver operating characteristic curve. Eighty patients were diagnosed with LPR and categorized as nonresponders (n = 19) and responders (n = 61). Proximal all reflux time and proximal longest reflux time in various MII parameters were higher in responders than in nonresponders (P = .0040 and .0216, respectively). Proximal all reflux time >0.000517% was a better cutoff value to predict responders with LPR as compared with the proximal longest reflux time >0.61 minutes (sensitivity + specificity: 1.317 vs 1.291). Proximal all reflux time in various 24-hour MII-pH monitoring parameters can be helpful to predict the response to PPI therapy in patients with LPR. These findings will help establish a personalized therapeutic scheme for patients with LPR.

Profile of the Change in Depression during Proton-Pump Inhibitor Therapy in Patients with Gastroesophageal Reflux Disease: Influence of the Mucosal Break.

Given the frequent concomitance between depression and gastroesophageal reflux disease (GERD), it is important to evaluate the change of depression in patients with GERD, especially considering the presence of esophageal mucosal breaks (MB). This study aimed to examine the change in the levels of depression in patients with GERD during proton-pump inhibitors (PPI) therapy. We designed a prospective cohort study to explore the profile of the alteration in depression with respect to the impact of esophageal MB. This study recruited 172 eligible patients with GERD between February 2016 and May 2018. The change in depression was defined as the difference between the respective Taiwanese Depression Questionnaire (TDQ) scores obtained at baseline and after PPI therapy. Multivariate linear regression models were used to estimate the factors associated with the change in depression. The results revealed statistically significant improvements in the TDQ score (mean score: baseline = 13.2, after PPI therapy = 10.9, p < 0.01, Cohen’s d = 0.30) during PPI therapy for GERD. Moreover, the MB was an independent variable associated with changes in the TDQ score [B = 3.31, 95% confidence interval (CI): (1.12, 5.51), p < 0.01] and the improvement in depression [odds ratio = 0.38, 95% CI: (0.17, 0.86), p = 0.02]. Our findings revealed that depressive symptoms improved slightly following PPI therapy. Moreover, MB was an unfavorable prognostic factor for the improvement in depression.

The Effect of Proton Pump Inhibitors on Insulin-Glucose Homeostasis in Patients With Type 2 Diabetes Mellitus

Introduction: Gastrin release from G cells stimulates cholecystokinin (CCK2) receptors throughout the body, most of which promote gastric acid secretion. However, gastrin also stimulates CCK2 receptors located elsewhere, including the islet of the pancreas. In turn, gastrin increases insulin secretion1. Gastrin also promotes pancreatic β cell neogenesis and replication. Proton pump inhibitors (PPIs) decrease the pH of the stomach and stimulate gastrin secretion, which may indirectly promote insulin secretion and improve hemoglobin A1c (HbA1c). Objective: To understand the effect of PPIs on insulin-glucose homeostasis (c-peptide, HbA1c, and glucose) in patients with type 2 diabetes mellitus (T2DM). Methodology: We retrospectively reviewed the charts of patients with T2DM at least 18 years of age who received care at AnMed Health facilities from Jan. 1, 2018 through Dec. 31, 2018 to compare HbA1c, C‐peptide, and glucose levels in patients with and without active PPI therapy. Slicer-dicer software was used to identify study population with diagnosis of T2DM and labs including both HbA1c and C-peptide. Out of total 215 patients satisfying inclusion criteria, 71 patients were on PPI. Statistical analyses were performed using SPSS version 20.0 (SPSS, Armonk, NY: IBM Corp). All values are presented as means ± SD. A p value of < 0.05 was considered to be significant. Independent T-test and chi-square test were performed to compare parameters in between groups. Results: The PPI and non‐PPI groups had no statistical difference regarding age, sex, race and BMI. There was no significant difference in HbA1c levels between PPI and non‐PPI groups (8.6% ± 2.1 vs 8.3% ± 2.0, respectively; p value = 0.37). However, we found a significant increase in C‐peptide levels (3.1 ng/mL ± 2.4 vs 2.4 ng/mL ± 2.3; p value = 0.037) and decrease in LDL levels (79.6 mg/dL ± 34.0 vs 89.73 mg/dL ± 32.9; p value = 0.046) in the PPI group compared to non-PPI group. In addition, there was a significantly greater prevalence of coronary artery disease in the PPI group (p = 0.01). Conclusion: PPI therapy in patients with T2DM was not associated with improved glycemic control. However, C-peptide levels were significantly higher in patients with T2DM who were on PPI therapy suggesting higher insulin secretion. The lack of difference in HbA1c levels may be a result of aggressive diabetic management by treating clinicians to achieve similar goal HbA1c in both groups. Further research is needed to understand the gastrin pathway as a potential option for improving glycemic control.

Proton Pump Inhibitors Reduce Duodenal Eosinophilia, Mast Cells, and Permeability in Patients With Functional Dyspepsia

Despite the growing recognition of duodenal alterations in the pathophysiology of functional dyspepsia (FD), the effect and mechanism of proton pump inhibitors (PPIs) or first-line therapy remain unclear. We studied duodenal and systemic alterations in relation to PPI therapy in patients with FD and healthy volunteers (HVs). We performed a prospective interventional study assessing symptoms (Patient Assessment of Gastrointestinal Symptom Severity Index), duodenal alterations, and systemic factors in patients with FD ("FD-starters") and HVs before and after PPI therapy (pantoprazole 40 mg once daily for 4 weeks). Duodenal mucosal eosinophils, mast cells and permeability were quantified. Luminal pH and bile salts were determined in duodenal aspirates. Procedures were also performed in PPI-refractory patients with FD ("FD-stoppers") before and 8 weeks after PPI withdrawal. Between- and within-group changes from baseline and associations with duodenal or systemic factors were analyzed using linear mixed models. The study was completed by 30 HV, 27 FD-starters, and 18 FD-stoppers. Symptoms and duodenal eosinophils, mast cells (all, P < .0001), and paracellular passage (P= .02) were significantly higher in FD-starters vs HVs and reduced with PPI therapy. Symptoms and duodenal immune cells also decreased in FD-stoppers off PPIs. In contrast, immune cells and permeability increased in HVs on PPIs. Dyspeptic symptoms correlated with eosinophils before and during PPI therapy, and increased eosinophils and permeability in HVs on PPIs were associated with changes in bile salts. We provide the first prospective evidence for eosinophil-reducing effects as a therapeutic mechanism of PPIs in FD, with differential effects in HVs pointing to a role of luminal changes. ClinicalTrials.gov, Number: NCT03545243.

High-resolution Manometry Determinants of Refractoriness of Reflux Symptoms to Proton Pump Inhibitor Therapy.

Background/AimsImpaired esophageal motility and disrupted esophagogastric junction (EGJ) on high-resolution manometry (HRM) have been associated with increased reflux severity in gastroesophageal reflux disease (GERD) patients. However, there are limited data evaluating HRM parameters in proton pump inhibitors (PPI) non-responders.MethodsClinical and endoscopic data, HRM and multichannel intraluminal impedance-pH studies performed of PPI therapy in patients with typical GERD symptoms were reviewed from 3 international centers. Frequency of GERD symptoms was assessed on and off PPI therapy in both non-responders (< 50% symptom improvement on PPI therapy) and responders. Rome IV definitions identified non-erosive reflux disease, reflux hypersensitivity, and functional heartburn. Univariate and multivariate analyses were performed to determine predictors of non-response.ResultsOf 204 patients, 105 were PPI non-responders and 99 were responders. Non-responders showed higher EGJ contractile integral values, and a lower frequency of type II and III EGJ morphology (P ≤ 0.03 for each comparison). Esophageal body diagnoses on HRM (fragmented peristalsis, ineffective esophageal motility, or absent peristalsis) did not predict non-response. On multivariate analysis, non-pathological acid exposure time (OR, 2.5; 95% CI, 1.2-5.0; P < 0.001), normal mean nocturnal baseline impedance values (OR, 2.7-2.4; 95% CI, 1.0-6.1; P < 0.05), normal EGJ contractile integral values (OR, 3; 95% CI, 1.3-7.4; P = 0.012), and presence of type I EGJ morphology (OR, 1.9; 95% CI, 1.0-3.4; P = 0.044) were associated with an unfavorable response to PPIs.ConclusionsIntact EGJ metrics on HRM complement normal reflux burden in predicting non-response to PPI therapy. HRM has value in the evaluation of PPI non-responders.

AGA Clinical Practice Update on Functional Heartburn: Expert Review

BEST PRACTICE ADVICE 1: A diagnosis of functional heartburn should be considered when retrosternal burning pain or discomfort persists despite maximal (double-dose) proton pump inhibitor (PPI) therapy taken appropriately before meals during a 3-month period. BEST PRACTICE ADVICE 2: A diagnosis of functional heartburn requires upper endoscopy with esophageal biopsies to rule out anatomic and mucosal abnormalities, esophageal high-resolution manometry to rule out major motor disorders, and pH monitoring off PPI therapy (or pH-impedance monitoring on therapy in patients with proven gastroesophageal reflux disease [GERD]), to document physiologic levels of esophageal acid exposure in the distal esophagus with absence of reflux-symptom association (ie, negative symptom index and symptom association probability). BEST PRACTICE ADVICE 3: Overlap of functional heartburn with proven GERD is diagnosed according to Rome IV criteria when heartburn persists despite maximal PPI therapy in patients with history of proven GERD (ie, positive pH study, erosive esophagitis, Barrett's esophagus, or esophageal ulcer), and pH impedance testing on PPI therapy demonstrates physiologic acid exposure without reflux-symptom association (ie, negative symptom index and symptom association probability). BEST PRACTICE ADVICE 4: PPIs have no therapeutic value in functional heartburn, the exception being proven GERD that overlaps with functional heartburn. BEST PRACTICE ADVICE 5: Neuromodulators, including tricyclic antidepressants, selective serotonin reuptake inhibitors, tegaserod, and histamine-2 receptor antagonists have benefit as either primary therapy in functional heartburn or as add-on therapy in functional heartburn that overlaps with proven GERD. BEST PRACTICE ADVICE 6: Based on available evidence, acupuncture and hypnotherapy may have benefit as monotherapy in functional heartburn, or as adjunctive therapy combined with other therapeutic modalities. BEST PRACTICE ADVICE 7: Based on available evidence, anti-reflux surgery and endoscopic GERD treatment modalities have no therapeutic benefit in functional heartburn and should not be recommended.

Proton pump inhibitors in patients with liver cirrhosis - a survey among hepatologists in Germany

Proton pump inhibitors (PPI) are one of the most frequently prescribed drugs worldwide. In particular, in patients with liver cirrhosis prescription rates up to 78 % have been reported. PPI may be a risk factor for nosocomial infections, spontaneous bacterial peritonitis and onset of hepatic encephalopathy. Aim of this survey was to assess the prescription practice of PPI in patients with cirrhosis in Germany. We performed a web-based survey among hepatologists and gastroenterologists. The invitations for the survey have been sent out via the newsletter of German gastroenterological societies (DGVS, BVGD and AUG). 61 persons have participated in the survey. Overall, high PPI prescription rates have been reported (58 % in inpatient and 44 % in outpatient setting). Almost half of the respondents reported that PPI are frequently prescribed without clear indication (such as abdominal discomfort). One third reported that the PPI therapy could be stopped after critical evaluation of the indication. 55 % of the respondents stated that according to their estimates PPI are associated with adverse reactions. Bleeding was only very rarely seen after termination of PPI treatment. PPI are frequently prescribed among patients with liver cirrhosis in Germany. Prescribers are aware of an unclear risk-benefit ratio. Further prospective data are urgently needed to increase evidence regarding indication and duration of PPI therapy in patients with cirrhosis.

Optimal Biopsy Protocol to Evaluate Histological Effectiveness of Proton Pump Inhibitor Therapy in Patients with Eosinophilic Esophagitis

Objective: Recent guidelines propose that both proton pump inhibitor (PPI) responders and nonresponders are included in eosinophilic esophagitis (EoE). Although multiple biopsies should be required to diagnose EoE because of patchy distribution of esophageal eosinophils, it is unclear whether multiple biopsies are required to evaluate histological effectiveness of PPI therapy. This study aimed to determine the optimal biopsy protocol after PPI therapy in patients with EoE. Methods: Of 110 EoE patients, 22 PPI nonresponders were enrolled. Intraepithelial eosinophils were counted in areas of high density in multiple biopsy specimens after PPI therapy. The prevalence of esophageal eosinophilia and peak eosinophil counts after PPI therapy was analyzed according to the biopsy sites and endoscopic findings. Positive predictive value (PPV) was calculated according to the number of biopsies. Results: Of 124 biopsies, 59 (47.6%) specimens showed esophageal eosinophilia (≥15 per high-power field). Eosinophil counts were significantly higher in specimens from the lower esophagus than in those from the upper esophagus but not in those from the middle esophagus. Prevalence of esophageal eosinophilia was 76.2, 40.9, and 24.3% in the lower, middle, and upper esophagus respectively. PPI nonresponders were diagnosed in all cases with 4 biopsy specimens obtained from the lower and middle esophagus, showing that PPV for non-effectiveness of PPI therapy was 0.910 (95% CI 0.773–1.000). The prevalence of esophageal eosinophilia and peak eosinophil counts was higher in cases with white plaques and linear furrows. Conclusion: Multiple biopsies should be required to evaluate histological effectiveness of PPI therapy in patients with EoE. Four biopsies from the lower and middle esophagus may be sufficient.

Adenocarcinoma arising in multiple hyperplastic polyps in a patient with Helicobacter pylori infection and hypergastrinemia during long-term proton pump inhibitor therapy

We report a case of developing multiple adenocarcinoma foci in multiple hyperplastic polyps in a patient with Helicobacter pylori infection and hypergastrinemia during long-term proton pump inhibitor (PPI) therapy. A 57-year-old man, who was undergoing hemodialysis for chronic renal failure, underwent an upper gastrointestinal endoscopy to elucidate the cause of anemia. Atrophic gastritis with H. pylori infection and multiple adenocarcinoma foci in multiple hyperplastic polyps were found in the endoscopic and histological examinations. Enterochromaffin-like micronests and parietal cell protrusion in the background of the polyps suggested the existence of hypergastrinemia. The serum gastrin level was markedly high-10,206pg/ml (normal range 37-172pg/ml). The cause of this marked hypergastrinemia was not autoimmune gastritis and gastrinoma. After discontinuing PPI therapy and successful eradication of H. pylori, the serum gastrin level decreased to normal range. These findings indicate that hypergastrinemia may be caused by long-term PPI therapy in patients with H. pylori infection. This case suggests that hypergastrinemia may mediate gastric carcinogenesis in patients with H. pylori infection.

Oropharyngeal pH Testing Does Not Predict Response to Proton Pump Inhibitor Therapy in Patients with Laryngeal Symptoms.

Predicting response to proton pump inhibitor (PPI) therapy in patients with laryngeal symptoms is challenging. The Restech Dx-pH probe is a transnasal catheter that measures oropharyngeal pH. In this study, we aimed to investigate the prognostic potential of oropharyngeal pH monitoring to predict responsiveness to PPI therapy in patients with laryngeal symptoms. We conducted a physician-blinded prospective cohort study at a single academic institution between January 2013 and October 2014. Adult patients with Reflux Symptom Index scores (RSI) ≥13 off PPI therapy were recruited. Patients underwent video laryngoscopy and 24-h oropharyngeal pH monitoring, followed by an 8- to 12-week trial of omeprazole 40 mg daily. Prior to and following PPI therapy, patients completed various symptom questionnaires. The primary outcome was the association between PPI response and oropharyngeal pH metrics. PPI response was separated into three subgroups based on the post-treatment RSI score and % RSI response: non-response=RSI ≥13; partial response=post-treatment RSI <13 and change in RSI <50%; and complete response=post-treatment RSI <13 and change in RSI ≥50%. The primary analysis utilized a multinomial logistic regression controlling for the pre-treatment RSI score. A secondary analysis assessed the relationship between the change in RSI (post-pre) and oropharyngeal pH metrics via ordinary least square regression. Thirty-four patients completed the study and were included in final analysis. Symptom response to PPI therapy was as follows: 50% no response, 15% partial response, and 35% complete response. Non-responders had a higher pre-treatment RSI (P<0.01). There were no significant differences in oropharyngeal acid exposure (below pH of 4.0, 5.0, 5.5, 6.0, and RYAN scores) between responder types. The secondary analysis noted a trend between lower PPI response and a greater total percent time below pH of 5.0 (P=0.03), upright percent time below pH of 5.0 (P=0.07), and RYAN supine (corrected; P=0.03), as well as an association between PPI response and greater decreases in the Anxiety Sensitivity Inventory (P<0.01), Brief Symptom Inventory-18 (P<0.01), and Negative Affect Scale (P<0.01). Oropharyngeal pH testing did not predict laryngeal symptom response to PPI therapy. Contrary to hypothesis, our study signaled that the degree of oropharyngeal acid exposure is inversely related to PPI response. In addition, reduction in negative affect and psychological distress parallels PPI response.

Proton-Pump Inhibitors Reduce Gastrointestinal Events Regardless of Aspirin Dose in Patients Requiring Dual Antiplatelet Therapy

BackgroundThe COGENT (Clopidogrel and the Optimization of Gastrointestinal Events Trial) showed that proton-pump inhibitors (PPIs) safely reduced rates of gastrointestinal (GI) events in patients requiring dual antiplatelet therapy (DAPT). However, utilization of appropriate prophylactic PPI therapy remains suboptimal, especially with low-dose aspirin. ObjectivesThe authors investigated the safety and efficacy of PPI therapy in patients receiving DAPT in low- and high-dose aspirin subsets. MethodsRandomized patients with available aspirin dosing information in COGENT (N = 3,752) were divided into “low-dose” (≤100 mg) and “high-dose” (>100 mg) aspirin groups. The primary GI and cardiovascular endpoints were composite upper GI events and major adverse cardiac events, respectively. All events were adjudicated by independent, blinded gastroenterologists and cardiologists. ResultsMedian duration of follow-up was 110 days. Low-dose aspirin users (n = 2,480; 66.1%) were more likely to be older, female, and have higher rates of peripheral artery disease, prior stroke, and hypertension, whereas high-dose aspirin users (n = 1,272; 33.9%) had higher rates of hyperlipidemia, smoking, a history of percutaneous coronary intervention, and were more than twice as likely to be enrolled from sites within the United States (80.4% vs. 39.8%). High-dose aspirin was associated with similar 180-day Kaplan-Meier estimates of adjudicated composite GI events (1.7% vs. 2.1%; adjusted hazard ratio: 0.88; 95% confidence interval: 0.46 to 1.66) and major adverse cardiac events (4.8% vs. 5.5%; adjusted hazard ratio: 0.73; 95% confidence interval: 0.48 to 1.11) compared with low-dose aspirin. Randomization to PPI therapy reduced 180-day Kaplan-Meier estimates of the primary GI endpoint in low-dose (1.2% vs. 3.1%) and high-dose aspirin subsets (0.9% vs. 2.6%; p for interaction = 0.80), and did not adversely affect the primary cardiovascular endpoint in either group. ConclusionsGastroprotection with PPI therapy should be utilized in appropriately selected patients with coronary artery disease requiring DAPT, even if the patients are on low-dose aspirin. (Clopidogrel and the Optimization of Gastrointestinal Events Trial [COGENT]; NCT00557921)

Factors associated with nonresponse to proton pump inhibitors therapy in patients referred for esophageal pH-impedance monitoring.

Nonresponse to proton pump inhibitors (PPI) concerns up to 40% of patients treated for gastroesophageal reflux disease (GERD). Identifying predictive factors of nonresponse might help to optimize patients' treatment. The aim of this study was to determine clinical factors associated with nonresponse to PPI therapy in patients referred for pH-impedance monitoring. One hundred and sixty-eight consecutive patients (105 females, mean age 52 years, range 17-83) were included between October 2011 and May 2013. Before the realization of high-resolution manometry and 24-hour pH-impedance monitoring they completed a questionnaire including Rome III criteria for functional dyspepsia and irritable bowel syndrome (IBS). Comparisons between patients with and without PPI response were performed using chi-square or analysis of variance tests. One hundred and twenty-six patients (83%) were considered as PPI nonresponders and 26 (17%) as responders. No significant difference was observed for age and body mass index. No manometric and pH-impedance profiles were identified as associated with PPI response. The percentage of patients with functional dyspepsia and IBS was higher in PPI nonresponders patients than in responders (65.6% and 27.2%, respectively, vs. 38.5% and 7.7%, P = 0.01 and P = 0.03). This study confirms that functional digestive disorders are more frequent in patients with persistent GERD symptoms on PPI and they might be indicative of nonresponse to PPI therapy.

Proton Pump Inhibitor Therapy in Eosinophilic Esophagitis: Current Role and Future Perspectives

Eosinophilic esophagitis (EoE) is a chronic, immune/antigen-mediated esophageal disease characterized by symptoms related to esophageal dysfunction, eosinophil-predominant inflammation, and lack of response to high-dose proton pump inhibitor (PPI) therapy. Responsiveness to PPI therapy in patients with suspected EoE has been historically assumed as evidence of gastroesophageal reflux disease (GERD), but this concept has rapidly changed over the past few years. A novel phenotype, termed PPI-responsive esophageal eosinophilia (PPI-REE), was described in 2011. PPI-REE refers to patients who appear to have EoE, but who achieve complete remission after PPI therapy. Currently, a PPI trial is mandatory before diagnosing EoE since 30–40 % of EoE patients will be eventually diagnosed with PPI-REE. Evolving evidence on PPI-REE suggests it is not simply GERD but actually a subphenotype of EoE, given the fact PPI-REE and EoE remain genetically and phenotypically indistinguishable. Instead of PPI-REE, the term PPI-responsive EoE might be more accurate to name this entity. PPI-REE might occur with either normal or pathological esophageal pH monitoring. PPI therapy can partially restore epithelial integrity and reverse allergic inflammation gene expression in PPI-REE. Whether esophageal barrier impairment is the cause of the effect of esophageal eosinophilia and whether PPI therapy primarily targets barrier or inflammation healing in PPI-REE have not been yet elucidated. The natural history of the disease, long-term doses, and duration of PPI therapy, as well as factors influencing symptom and/or inflammation relapse remain yet unknown. The mechanism as to why among identical patients, some respond to PPI therapy (PPI-REE) while others do not (EoE), warrants further research.

Predictive factors of response to proton pump inhibitors in korean patients with gastroesophageal reflux disease.

Background/AimsProton pump inhibitors (PPIs) are widely used in the treatment of gastroesophageal reflux disease (GERD). However, some patients fail to respond to PPI therapy. We investigated the efficacy of response to PPI therapy in patients with GERD symptoms.MethodsA total of 179 subjects with GERD symptoms were prospectively enrolled and diagnosed with non-erosive reflux disease (NERD, n = 100) and erosive reflux disease (n = 79) by gastroscopy and Bernstein test and/or 24-hour esophageal pH testing. Subjects then received a standard dose of daily PPI therapy for at least 4 weeks. PPI therapy response was evaluated using questionnaires including questions about demographics, GERD symptoms, GERD impact scale, Epworth sleepiness scale, Pittsburgh sleep quality index (PSQI), hospital anxiety and depression scale, and abbreviated version of the World Health Organization quality of life scale.ResultsThe rates of complete (≥ 80%), satisfactory (≥ 50%), partial (< 50%), and refractory response in the 179 participants were 41.3%, 30.2%, 18.4%, and 10.1%, respectively. Thus, overall response rate (complete and satisfactory responses) was 71.5%. Multivariate analysis showed body mass index < 23 kg/m2 (OR, 2.20; 95% CI, 1.12–4.34), higher total PSQI score (OR, 1.20; 95% CI, 1.05–1.35), history of psychotherapy or neuropsychiatric medication (OR, 2.44; 95% CI, 1.23–4.85), and NERD (OR, 3.30; 95% CI, 1.54–7.11) were associated with poor response to PPI therapy.ConclusionsPsychological factors, sleep dysfunction, body mass index < 23 kg/m2, and NERD seem to be the major factors that lead to a poor response to PPI treatment in patients with GERD symptoms.

Risk factors of incomplete response to proton pump inhibitor therapy in patients with mild erosive esophagitis

Summary Background Incomplete symptom resolution to proton pump inhibitor (PPI) therapy is a common problem in the treatment of gastroesophageal reflux disease (GERD). The aims of this study were (1) to examine the rate of incomplete symptom response following 8-week PPI therapy in patients with mild erosive esophagitis (Los Angeles Grade A/B erosive esophagitis) and (2) to determine the independent factors predicting incomplete symptom response in patients with mild erosive esophagitis. Methods From January 2010 to July 2012, symptomatic GERD patients with endoscopic findings of Los Angeles Grade A or B erosive esophagitis were recruited for the study and received esomeprazole 40 mg daily for 8 weeks. The characteristics of eligible patients including clinical factors, endoscopic findings, Helicobacter pylori status, and CYP2C19 (cytochrome P450 2C19) genotype were checked on enrollment. Patients were asked to record symptoms with diary cards during the follow-up period. The major outcome measurement was incomplete symptom response. Results In total, 232 patients (male/female, 126/106) participated in this study. Following 8-week esomeprazole therapy, 50 (21.6%) of the patients had incomplete symptom response. Univariate analysis showed that sex, alcohol consumption, underlying diseases, regurgitation of food, chest pain, globus, and insomnia were associated with incomplete symptom response ( p = 0.049, p = 0.006, p = 0.023, p = 0.010, p = 0.013, p = 0.009, and p p = 0.015] and insomnia (95% CI: 1.289–3.018; p = 0.002) were independent risk factors for incomplete symptom response with odds ratio (OR) = 2.4 and OR = 2.0, respectively. Conclusion Of the patients with Los Angeles Grade A/B erosive esophagitis, 21.6% failed to have complete symptom resolution following 8-week PPI therapy. Globus and insomnia are two independent factors predicting incomplete symptom response in patients with mild erosive esophagitis.

Review article: proton pump inhibitor therapy for suspected eosinophilic oesophagitis

Recent advances in eosinophilic oesophagitis (EoE) have confirmed the existence of a new disease phenotype, proton pump inhibitor (PPI)-responsive oesophageal eosinophilia (PPI-REE). To summarise evidence supporting the use of PPI therapy in patients with suspected EoE (oesophageal dysfunction plus >15 eos/HPF in oesophageal biopsies). A literature search was conducted through MEDLINE, using the MeSH search terms 'eosinophilic oesophagitis', 'proton pump inhibitors' and 'oesophageal eosinophilia'. Relevant articles and their reference lists were identified through manual review. Ten articles, including 258 patients with suspected EoE (152 children, 106 adults) undergoing clinico-histological re-evaluation after PPI therapy, were identified. In children, clinical response ranged from 78% to 86% and histological remission from 23% to 40%. In adults, symptom response ranged from 25% to 80% and histological remission from 33% to 61%. Among PPI-REE patients with oesophageal pH-monitoring, 35 showed pathological and 10 normal studies. PPI-REE was significantly commoner with documented gastro-oesophageal reflux disease (GERD) when compared to patients with negative pH monitoring (70% vs. 29%, P<0.001). Symptom improvement/resolution occurred in 50-85% of patients without histological remission on PPI therapy. Six PPI-REE patients demonstrated clinico-histological relapse on PPI therapy. At least one third of patients with suspected EoE achieve clinico-histological remission on PPI therapy. Response is more limited in children compared with that in adults. pH monitoring does not accurately predict response to PPI therapy, albeit histological remission is significantly higher, up to 70%, upon documented GERD. Symptom improvement is common with PPI therapy despite persistent eosinophilic infiltration.

The effects of increasing body mass index on heartburn severity, frequency and response to treatment with dexlansoprazole or lansoprazole

BackgroundHigher body mass index (BMI) is a recognised risk factor for gastro-oesophageal reflux disease (GERD). Data regarding the impact of BMI on proton pump inhibitor (PPI) therapy are conflicting.AimTo assess the impact of BMI on baseline heartburn symptom severity and frequency and response to PPI therapy in patients with non-erosive GERD (NERD) or erosive oesophagitis (EO).MethodsIn post hoc analyses of phase 3 trial data, 621 NERD and 2692 EO patients were stratified by BMI (<25, 25 to <30 and ≥30 kg/m2). NERD patients received either dexlansoprazole MR 30 mg or placebo daily for 4 weeks. EO patients received either dexlansoprazole MR 60 mg or lansoprazole 30 mg for 8 weeks. Symptom frequency and severity were assessed at baseline and subsequently by daily diary.ResultsIn both the NERD and EO cohorts, baseline heartburn severity increased with increasing BMI. The impact of PPI therapy on the reduction in heartburn symptom frequency and severity in both NERD and EO patients was similar across BMI categories. EO healing rates in patients treated with dexlansoprazole but not lansoprazole were higher in obese patients compared with those with a BMI <30 kg/m2. Differences between the PPIs were small.ConclusionsThe PPIs evaluated in this study reduced the frequency and severity of 24-h heartburn regardless of baseline BMI. In addition, because patients with higher BMI have more severe symptoms at baseline, they may experience greater therapeutic gain with dexlansoprazole (NERD and erosive oesophagitis) and possibly lansoprazole (erosive oesophagitis) treatment.