Effect Of Proton Pump Inhibitor Treatment Research Articles

Proton pump inhibitor treatment is associated with acute-on-chronic liver failure in patients with advanced cirrhosis.

Acute-on-chronic liver failure (ACLF) is a fatal complication of cirrhosis. Hence, identification of risk factors for ACLF is crucial. Previous studies have linked proton pump inhibitor (PPI) treatment to complications of cirrhosis, however, a possible effect of PPI treatment on the risk of ACLF has not been investigated yet. Therefore, the present study aimed to characterize the impact of PPI treatment on ACLF development. A total of 642 patients hospitalized due to complications of cirrhosis were retrospectively identified, and PPI treatment during an observation period of 3 years following the hospitalization was reviewed. Subsequently, 74 patients with newly initiated PPI treatment at the time of hospitalization (PPI group) were 1:1 propensity score matched to 74 patients who received no PPI treatment (no-PPI group). Primary end point was the development of ACLF during the observation period, and secondary endpoints were mortality and upper gastrointestinal bleeding. PPI and no-PPI groups had comparably severe chronic liver disease at baseline. Nevertheless, the cumulative incidence of ACLF in the presence of death as competing risk was markedly higher in the PPI group compared with the no-PPI group. ACLF-related deaths contributed significantly to a higher 3-year mortality in the PPI group. Uni and multivariable competing risk regression models confirmed that PPI treatment was an independent predictor of ACLF in the study collective (subdistribution HR: 1.892, 95% CI: 1.092-3.281, p = 0.023). The impact of PPI treatment on ACLF development was particularly strong in patients with a model for end-stage liver disease score >12. Upper gastrointestinal bleeding was slightly less frequent in the PPI group. The present results indicate that PPI treatment could be a risk factor for ACLF in patients with advanced cirrhosis.

Meta-Analysis of the Effect of Proton Pump Inhibitors on Obstructive Sleep Apnea Symptoms and Indices in Patients with Gastroesophageal Reflux Disease

This study was designed to assess evidence for an association between the treatment of gastroesophageal reflux disease (GERD) with proton pump inhibitors (PPIs) and improvement in obstructive sleep apnea (OSA). We conducted a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies to evaluate the treatment effect of PPIs on OSA symptoms and indices in patients with GERD. EMBASE, MEDLINE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov were reviewed up to October 2014. From 238 articles, two randomized trials and four prospective cohort studies were selected. In four cohort studies there were no differences in the apnea-hypopnea indices before and after treatment with PPIs (standard mean difference, 0.21; 95% confidence interval, −0.11 to 0.54). There was moderate heterogeneity among these studies. Two cohort studies revealed significantly decreased apnea indices after treatment (percent change, 31% and 35%), but one showed no significant difference. A significant improvement in the Epworth Sleepiness Scale was observed in three cohort studies and one trial. The frequency of apnea attacks recorded in diaries was decreased by 73% in one trial. In conclusion, available studies do not provide enough evidence to make firm conclusions about the effects of PPI treatment on OSA symptoms and indices in patients with concomitant GERD. Controlled clinical trials with larger sample sizes are needed to evaluate these associations. We recommend PPIs in OSA patients with concomitant GERD to treat reflux symptoms. This treatment may improve the quality of sleep without any effect on apnea-hypopnea indices.

Effect of Proton-Pump Inhibitor Treatment on Symptoms and Quality of Life in GERD Patients Depends on the Symptom-reflux Association

Gastroesophageal reflux disease patients demonstrate various pathophysiologic backgrounds. Therefore, a heterogeneous response to proton-pump inhibitor (PPI) treatment can be expected. We investigated the effect of short-term PPI treatment on symptoms and quality of life (QOL) in primary care patients with and without pathologic esophageal acid exposure and in presence or absence of a positive association between symptoms and reflux episodes. Seventy-four heartburn patients were categorized into 4 groups according to positive or negative symptom-reflux association, as expressed in symptom index, symptom sensitivity index, and symptom association probability (SAP) and presence or absence of pathologic reflux, defined as esophageal pH<4%>6% of the time (pH+/pH-). Overall and specific reflux symptoms were assessed 1 week before and the last week during a 2-week course of 40-mg esomeprazole daily. The QOL was scored by the Quality of Life in Reflux and Dyspepsia questionnaire 2 weeks before treatment and directly after. Using the SAP to assess symptom-reflux associations, the 4 groups [SAP+pH+(n=40); SAP+pH-(n=12); SAP-pH+(n=10); SAP-pH-(n=10)] had similar demographic characteristics. The SAP-pH- subgroup had the least overall symptom reduction (P<0.01) and in the SAP+pH+ subgroup the greatest heartburn symptom reduction was found (P<0.02). The residual symptom scores on treatment were lowest in SAP+pH+ and highest in SAP-pH- subgroups and relatively high in the SAP+pH-. QOL was severely reduced and SAP-pH- patients had the lowest QOL overall. Similar findings were made using symptom index and symptom sensitivity index. Symptomatic reflux patients without evidence of reflux disease on a 24-hour pH recording responded less favorably to PPI treatment than patients with a positive symptom-reflux association or with pathologic reflux.

Systematic reviews of the clinical effectiveness and cost-effectiveness of proton pump inhibitors in acute upper gastrointestinal bleeding

To evaluate the clinical effectiveness and cost-effectiveness of proton pump inhibitors (PPIs) in the prevention and treatment of acute upper gastrointestinal (UGI) haemorrhage, as well as to compare this with H2-receptor antagonist (H2RA), Helicobacter pylori eradication (in infected patients) or no therapy, for the prevention of first and/or subsequent bleeds among patients who continue to use non-steroidal anti-inflammatory drugs (NSAIDs). Also to evaluate the clinical effectiveness of PPI therapy, compared with other treatments, for the prevention of subsequent bleeds in patients who had previously experienced peptic ulcer (PU) bleeding. Electronic databases and major conference proceedings were searched up to February 2006. Data were collected from the systematic reviews addressing each research objective. These were then entered into an economic model to compare the costs and quality-adjusted life-days of alternative management strategies over a 28-day period for patients who have had UGI bleeding. A Markov model with a Monte Carlo simulation used data from the systematic reviews to identify the most cost-effective treatment strategy for the prevention of UGI bleeding (first and subsequent) among NSAID users using an outcome of costs per quality-adjusted life-years (QALYs) over a lifetime from age 50 years. PPI treatment initiated after endoscopic diagnosis of PU bleeding significantly reduced re-bleeding and surgery compared with placebo or H2RA. Although there was no evidence of an overall effect of PPI treatment on all-cause mortality, PPIs significantly reduced mortality in subgroups when studies conducted in Asia were examined in isolation or when the analysis was confined to patients with high-risk endoscopic findings. PPI treatment initiated prior to endoscopy in UGI bleeding significantly reduced the proportion of patients with stigmata of recent haemorrhage (SRH) at index endoscopy compared with placebo or H2RA, but there was no evidence that PPI treatment affected clinically important outcomes. Giving oral PPI both before and after endoscopy, with endoscopic haemostatic therapy (EHT) for those with major SRH, is preferred to all others on cost-effectiveness grounds at any threshold over 25,000 pounds per QALY, even if only short-term effects are taken into account, and at any threshold over 200 pounds per life-year gained if long-term effects are included. The risk of NSAID-induced endoscopic gastric and duodenal ulcers was reduced by standard doses of PPI and misoprostol, and double doses of H2RAs. Standard doses of H2RAs reduced the risk of endoscopic duodenal ulcers. PPIs reduced NSAID-induced dyspepsia. PPIs were superior to misoprostol in preventing recurrence of NSAID-induced endoscopic duodenal ulcers, but PPIs were comparable to misoprostol in preventing the recurrence of NSAID-induced endoscopic gastric ulcers. Full-dose misoprostol reduced bleeding, perforation or gastric outlet obstruction due to NSAID-induced ulcers, but misoprostol was poorly tolerated and associated with frequent adverse effects. H. pylori eradication treatment was equally effective with PPI treatment for the primary or secondary prevention of endoscopic ulcers in NSAID users. H. pylori eradication treatment was more effective than placebo for the primary prevention of endoscopic PU and for the prevention of re-bleeding from PU in NSAID users. With regard to primary and secondary prevention of bleeding PU in NSAID users, the two most cost-effective strategies are H. pylori eradication alone, and H. pylori eradication followed by misoprostol (substituted by a PPI, if misoprostol is not tolerated) at an additional 4810 pounds per QALY. In patients who had previously experienced a bleed from a PU, re-bleeding was less frequent after H. pylori eradication therapy than after non-eradication antisecretory therapy, whether or not the latter was combined with long-term maintenance antisecretory therapy. PPI treatment compared with placebo or H2RA reduces mortality following PU bleeding among patients with high-risk endoscopic findings, and reduces re-bleeding rates and surgical intervention. PPI treatment initiated prior to endoscopy in UGI bleeding significantly reduces the proportion of patients with SRH at index endoscopy but does not reduce mortality, re-bleeding or the need for surgery. The strategy of giving oral PPI before and after endoscopy, with EHT for those with major SRH, is likely to be the most cost-effective. Treatment of H. pylori infection was found to be more effective than antisecretory therapy in preventing recurrent bleeding from PU. H. pylori eradication alone or eradication followed by misoprostol (with switch to PPI, if misoprostol is not tolerated) are the two most cost-effective strategies for preventing bleeding ulcers among H. pylori-infected NSAID users, although the data cannot exclude PPIs also being cost-effective. Further large randomised controlled trials are needed to address areas such as PPI administration prior to endoscopic diagnosis, different doses and administration of PPIs, as well as the primary and secondary prevention of UGI bleeding.

Effect of Antisecretory Therapy on Atypical Symptoms in Gastroesophageal Reflux Disease

The effect of proton pump inhibitor (PPI) therapy on extraesophageal or atypical manifestations of gastroesophageal reflux disease (GERD) remains unclear. This study aimed to evaluate the prevalence of atypical manifestations in patients with acid reflux disease and the effect of PPI treatment. Patients with symptoms and signs suggestive of reflux were enrolled. Erosive esophagitis was stratified using the Los Angeles classification. Demographic data and symptoms were assessed using a questionnaire and included typical symptoms (heartburn, regurgitation, dysphagia, odynophagia), and atypical symptoms (e.g., chest pain, sialorrhea, hoarseness, globus sensation, chronic coughing, episodic bronchospasm, hiccup, eructations, laryngitis, and pharyngitis). Symptoms were reassessed after a 3-month course of b.i.d. PPI therapy. A total of 266 patients with a first diagnosis of GERD (erosive, 166; non-erosive, 100) were entered in the study. Presentation with atypical symptoms was approximately equal in those with erosive GERD and with non-erosive GERD, 72% vs 79% (P = 0.18). None of the study variables showed a significant association with the body mass index. PPI therapy resulted in complete symptom resolution in 69% (162/237) of the participants, 12% (28) had improved symptoms, and 20% (47) had minimal or no improvement. We conclude that atypical symptoms are frequent in patients with GERD. A trial of PPI therapy should be considered prior to referring these patients to specialists.

Systematic review and meta‐analysis: proton‐pump inhibitor treatment for ulcer bleeding reduces transfusion requirements and hospital stay – results from the Cochrane Collaboration

Proton-pump inhibitors reduce re-bleeding and surgical intervention, but not mortality, after ulcer bleeding. To examine the effects of proton-pump inhibitor treatment on transfusion requirements and length of hospital stay in patients with ulcer bleeding. For the Cochrane Collaboration meta-analysis of randomized-controlled trials of proton-pump inhibitor therapy for ulcer bleeding, outcomes of transfusion requirements and hospital stay were summarized, respectively, as mean (+/-s.d.) units transfused and hospital days. We calculated weighted mean difference with 95% confidence interval. We also performed subgroup analyses according to geographical origin of the randomized-controlled trials. There was significant heterogeneity among randomized-controlled trials for either outcome. Overall, proton-pump inhibitor treatment marginally reduced transfusion requirements (WMD = -0.6 units; 95% CI: -1.1 to 0; P = 0.05) and length of hospitalization (WMD = -1.1 days; 95% CI: -1.5 to -0.7; P < 0.0001). Most of the randomized-controlled trials did not state precise criteria for administering blood transfusion and discharging patients, thereby limiting the strength of conclusions on the pooled effects. Proton-pump inhibitor treatment for ulcer bleeding produces small, but potentially important, reductions in transfusion requirements and length of hospitalization.

Effects of Long-term Treatment with Proton Pump Inhibitors in Gastro-oesophageal Reflux Disease on the Histological Findings in the Lower Oesophagus

Background: The application of hyperplasia of the basal cell layer and elongation of the papillae in the squamous epithelium of the distal oesophagus, as histological criteria for the diagnosis of gastro-oesophageal reflux disease (GORD), continues to be controversial. An unanswered question is whether these changes may regress under long-term treatment with proton pump inhibitors (PPI). This fact prompted us to investigate the effect of PPI treatment on the histological changes observed in the lower oesophagus. Methods: 295 patients with endoscopically confirmed erosive GORD were investigated by endoscopy/biopsy prior to and during the course of a 12-month PPI treatment regimen (8 weeks acute treatment with 30 mg lansoprazole/day followed by long-term treatment with 15 or 30 mg lansoprazole or 20 mg omeprazole/day). The parameters studied were the frequency of ulcers and erosions and the hyperplasia of the basal cell layer and elongation of the papillae prior to treatment and on day 56 (D56), after 6 months (M6) and after 12 months (M12) of treatment. Results: In the various treatment groups, the results showed no statistically significant differences. Ulcers and erosions (prior to treatment 21% and 31%, respectively) were detected statistically significantly less frequently under PPI treatment (ulcers, D56: 1%, M6 and M12, 0%; erosions, D56: 2%, M6: 4%, M12, 3%). While high-grade hyperplasia of the basal cell layer and elongation of the papillae was found in 51% of the cases prior to treatment, the corresponding figures were only 3% (D56, M6) and 2% (M12). In contrast, the percentage of cases with normal oesophageal epithelium increased from 8% before treatment to 55% (D56), 66% (M6) and 63% (M12). Conclusions: Our study shows not only that erosions and ulcers heal under PPI treatment, but also that hyperplasia of the basal cell layer and elongation of papillae in the squamous epithelium of the oesophageal mucosa may normalize, and are thus presumably not 'normal physiological variants'.