Are proton pump inhibitors associated with the development of community-acquired pneumonia? A meta-analysis

This study was presented at the American College of Chest Physicians meeting in Pittsburgh (PA, USA) in October 2011. The study objective was to evaluate the association of proton pump inhibitors (PPIs) and community-acquired pneumonia (CAP). The design was a meta-analysis of nine case-controlled and cohort studies. 120,863 pneumonia cases from 1987 to 2006 were included in the meta-analysis. PubMed and Ovid Medline were searched from inception through May 2011 by two investigators independently using keywords: PPI, pneumonia, CAP, anti-ulcer, antacid, omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole. This meta-analysis only included case-controlled and cohort studies that were published in full in English and evaluated PPI use and CAP incidence. Studies were excluded if they included the following patients: pediatric, Helicobacter pylori treatment and critically ill. Bibliographies of recent review articles and systematic reviews were hand-searched. Quality of studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. Two investigators independently extracted data into standardized data collection forms that were confirmed by a third investigator. Data were analyzed based on current use of PPIs, duration of PPI use (<30 days or >180 days) and PPI dose (high vs low). Overall association of PPI and CAP was analyzed using the random effects model (Comprehensive Meta analysis(?) Version 2.0). Nine studies met all criteria for the primary outcome. Newcastle-Ottawa Quality Assessment Scale scores ranged from 4 to 8 out of 9. Current use of PPIs (odds ratio [OR]: 1.39; 95% CI: 1.09-1.76), PPI use <30 days (OR: 1.65; 95% CI: 1.25-2.19), PPI high dose (OR: 1.50; 95% CI: 1.33-1.68) and PPI low dose (OR: 1.17; 95% CI: 1.11-1.24) were significantly associated with CAP. There was no association between CAP and PPI use >180 days (OR: 1.10; 95% CI: 1.00-1.21). In conclusion, patients currently receiving PPIs, particularly <30 days or high dose, showed an association with CAP. Practitioners need to be vigilant about adverse effects of PPIs and consider alternative therapies.     

Long-term use of proton pump inhibitors in GORD – help or hindrance?

Many patients with gastro-oesophageal reflux disease (GORD) experience chronic relapses and require maintenance therapy for symptomatic relief. This article reviews possible mechanisms for chronic relapse in GORD, and discusses the risks and benefits of proton pump inhibitors as maintenance therapy for this disease. Recent medical literature was reviewed to gather information about proton pump inhibitor therapy and GORD. The reports indicated that the tendency to relapse in GORD is probably related to ongoing motor defects and to the acid rebound that follows successful healing therapy. Proton pump inhibitors are very effective in maintaining symptomatic and endoscopic remission in GORD. Limitations of proton pump inhibitor therapy have largely so far been clinically irrelevant. Most side-effects are inherent consequences of any form of acid suppression therapy, and include hypergastrinaemia and rebound hyperacidity upon discontinuation of therapy. We conclude that the therapeutic balance tips toward proton pump inhibitors for treatment of GORD because their limitations are largely surpassed by excellent clinical efficacy, tolerance, and lack of serious adverse effects.     

Systematic review: Is there excessive use of proton pump inhibitors in gastro-oesophageal reflux disease?

BACKGROUND: Proton-pump inhibitors are often recommended for continuous use in gastro-oesophageal reflux disease, but this may not be necessary in all patients. AIM: To ascertain the level of evidence for alternative strategies for proton-pump inhibitor treatment in gastro-oesophageal reflux disease. METHODS: We searched for observational or interventional studies examining alternatives to continuous proton-pump inhibitor treatment in gastro-oesophageal reflux disease. RESULTS: Non-randomized studies suggest that some patients with gastro-oesophageal reflux disease, including some with erosive oesophagitis, may be adequately maintained on proton-pump inhibitor therapy given less frequently than once daily. However, the results may not be generalizable. Four high quality randomized-controlled trials compared 'on-demand' proton-pump inhibitor and placebo treatment in endoscopy-negative reflux disease; all found this effective for most patients. One high quality randomized-controlled trial found intermittent courses of a proton-pump inhibitor or H2-receptor antagonist in erosive oesophagitis or endoscopy-negative reflux disease adequate for almost half of the patients studied. Up to 80% of patients on continuous high-dose proton-pump inhibitor treatment for gastro-oesophageal reflux disease can be 'stepped down' to less intensive therapy. CONCLUSIONS: On-demand proton-pump inhibitor treatment may be appropriate in endoscopy-negative reflux disease. In gastro-oesophageal reflux disease, patients taking more than once daily or high-dose proton-pump inhibitor treatment, a step down to once daily or standard dose therapy should be attempted.     

Long-term use of proton pump inhibitors in GORD – help or hindrance?

Many patients with gastro-oesophageal reflux disease (GORD) experience chronic relapses and require maintenance therapy for symptomatic relief. This article reviews possible mechanisms for chronic relapse in GORD, and discusses the risks and benefits of proton pump inhibtors as maintenance therapy for this disease. Recent medical literature was reviewed to gather information about proton pump inhibitor therapy and GORD. The reports indicated that the tendency to relapse in GORD is probably related to ongoing motor defects and to the acid rebound that follows sucessful healing therapy. Proton pump inhibitors are very effective in maintaining symptomatic and endoscopic remission in GORD. Limitations of proton pump inhibitor therapy have largely so far been clinically irrelevant. Most side-effects are inherent consequences of any form of acid suppression therapy, and include hypergastrinaemia and rebound hyperacidity upon discontinuation of therapy. We conclude that the therapeutic balance tips toward proton pump inhibitors for treatment of GORD because their limitations are largely surpassed by excellent clinical efficacy, tolerance, and lack of serious adverse effects.     

Prescribing proton pump inhibitors: is it time to pause and rethink?

Proton pump inhibitors (PPIs) are among the most widely used agents in the world. The prevalence of reflux disease is increasing, as is the incidence of oesophageal adenocarcinoma, a complication that is strongly correlated with chronic reflux disease. Although these agents are generally safe, a number of potential side effects have been described and a careful assessment of the risks and benefits of PPI therapy is required in all patients being prescribed long-term therapy. Overutilization of PPIs is a problem in clinical practice and needs further attention. PPI use has been associated with osteoporosis and bone fracture, hypomagnesaemia, the development of gastric polyps, enteric infections, interstitial nephritis and pneumonia. Patients on long-term therapy should be periodically evaluated for the indications for continued therapy. Despite widespread publicity in the lay press, and regulatory guidance regarding a number of associations, the evidence for serious side effects is poor and the risk of confounding remains a real possibility for many associations. Patients are more concerned about the absolute risk of developing a complication than a relative risk. The absolute risk of all the complications attributed to PPIs is low and patients who need long-term PPI therapy need a clear discussion of the available data on the risk of therapy and also a discussion of the risk of continued reflux.     

Is it possible to predict treatment response to a proton pump inhibitor in functional dyspepsia?

BACKGROUND: The efficacy of proton pump inhibitors in functional dyspepsia is modest and the prognostic factors are almost unknown. METHODS: Data were pooled on patients (n = 826) with a diagnosis of functional dyspepsia from two placebo-controlled trials who were treated with omeprazole, 10 or 20 mg once daily, for 4 weeks. Self-administered questionnaires for the assessment of symptoms and health-related quality of life were completed before entry, and epigastric pain/discomfort was recorded on diary cards. Treatment success was defined as the complete absence of epigastric pain/discomfort on each of the last 3 days of week 4. Prognostic factors were identified by multiple logistic regression analysis. RESULTS: The most discriminating predictor of treatment success (P < 0.0001) was the number of days with epigastric pain/discomfort during the first week of treatment. Fewer days with symptoms during the first week led to higher response rates at 4 weeks. In addition, age > 40 years, bothersome heartburn, low scores for bloating, epigastric pain and diarrhoea, history of symptoms for < 3 months and low impairment of vitality at baseline were identified as positive predictors of outcome. CONCLUSIONS: Early response to treatment with a proton pump inhibitor, during the first week, seems to predict the outcome after 4 weeks in patients with functional dyspepsia.