Head-to-head comparison of H2-receptor antagonists and proton pump inhibitors in the treatment of erosive esophagitis： A meta-analysis

AIM: To systematically evaluate the efficacy of H2-receptor antagonists (H2RAs) and proton pump inhibitors in healing erosive esophagitis (EE). METHODS: A meta-analysis was performed. A literature search was conducted in PubMed, Medline, Embase, and Cochrane databases to include randomized controlled head-to-head comparative trials evaluating the efficacy of H2RAs or proton pump inhibitors in healing EE. Relative risk (RR) and 95% confidence interval (CI) were calculated under a random-effects model. RESULTS: RRs of cumulative healing rates for each comparison at 8 wk were: high dose vs standard dose H2RAs, 1.17 (95%CI, 1.02-1.33); standard dose proton pump inhibitors vs standard dose H2RAs, 1.59 (95%CI, 1.44-1.75); standard dose other proton pump inhibitors vs standard dose omeprazole, 1.06 (95%CI, 0.98-1.06). Proton pump inhibitors produced consistently greater healing rates than H2RAs of all doses across all grades of esophagitis, including patients refractory to H2RAs. Healing rates achieved with standard dose omeprazole were similar to those with other proton pump inhibitors in all grades of esophagitis. CONCLUSION: H2RAs are less effective for treating patients with erosive esophagitis, especially in those with severe forms of esophagitis. Standard dose proton pump inhibitors are significantly more effective than H2RAs in healing esophagitis of all grades. Proton pump inhibitors given at the recommended dose are equally effective for healing esophagitis.     

Clostridium difficile infection in the community: Are proton pump inhibitors to blame?

Once a nosocomial disease,Clostridium difficile infection(CDI)now appears frequently in the community in the absence of exposure to antibiotics.Prior studies have shown that patients with community-acquired CDI are younger,more likely to be female,and have fewer comorbidities compared to patients with hospital-associated CDI.Because most studies of CDI are hospitalbased,comparatively little is known about communityacquired CDI.The recent study by Chitnis has received widespread attention because it used active surveillance to capture all cases of community-acquired CDI within a large population and assessed key risk factors.The authors found that low-level healthcare exposure and proton pump inhibitor use were common among those with non-antibiotics associated,community-acquired CDI.In this commentary,we discuss the changing epidemiology of community-acquired CDI and the evidence basis for the controversial association between proton pump inhibitors and community-acquired CDI.     

Potassium-competitive acid blockers - are they the next generation of proton pump inhibitors?

The modern lifestyle caters to an increase in the incidence of peptic ulcer disease, gastroesophageal reflux disease and several other acid-related conditions of the gut. The drugs to prevent these conditions work either through H2 receptor blockade or inhibition of the H⁺, K⁺ ATPase enzyme. Although proton pump inhibitors have been proven to be efficacious, they have a slow onset of action with limited resolution of symptoms in most patients. Potassium-competitive acid blockers (P-CABs) are novel drugs that bind reversibly to K⁺ ions and block the H⁺, K⁺ ATPase enzyme, thus preventing acid production. P-CABs have a fast onset of action and have dose-dependent effects on acid production. Animal studies exist that differentiate the better results of P-CABs from proton pump inhibitors; further human trials will give a comprehensive picture of the results and will help to elucidate the therapeutic benefits of this new group of drugs.     

Proton pump inhibitors and H. pylori infection: Why the concern?

Summary Proton pump inhibitor therapy, even on a short-term basis, is associated with a decrease in antral gastritis and an increase in gastritis of the body. On a long-term basis, some series show the development of atrophic gastritis and some show none or hardly any. All studies fail to show or to report any significant increase in the prevalence of intestinal metaplasia with long-term PPI therapy. If one wants to determine whether PPIs cause atrophic gastritis with intestinal metaplasia, then the angularis primarily and the gastric antrum secondarily need to be studied because that is where most IM resides in the intestinal types of cancer. Instead of focusing on the angularis an antrum, the studies have evaluated biopsies from the gastric body, the least likely spot to be intestinalized in association with the intestinal type of gastric cancer. H. pylori is associated with both intestinal and diffuse types of gastric cancer. Obtaining an answer to the question of whether PPI therapy or any other type of therap increases gastric cancer risk in H. pylori-positive patients will require epidemiologic studies in which cancer is the end point. Intermediate theoretic markers are not available for diffuse cancers. If intermediate markers are used for the intestinal type of gastric cancer, then atrophic gastritis with intestinal metaplasia might provide some insight on theoretical grounds. However, the published long-term studies to date have not addressed that question because of where they have focused the biopsy sampling, and/or because of failure to report data on intestinal metaplasia.     

Chronic use of proton pump inhibitors: is the risk of osteoporosis and fractures real?

Proton pump inhibitors (PPI) are one of the most widely used groups of drugs and their potential toxicity is periodically reviewed, emphasizing aspects originally considered secondary. The present review analyzes the physiological and pharmacological bases and the scarce clinical evidence for a potential association between the continued administration of PPI and the development of osteoporosis and bone fractures. Both disorders are clearly related to calcium homeostasis and are highly important in elderly patients due to their poor general prognosis and disabling consequences.     

Does proton pump inhibition change the on-treatment anti-Xa activity in xabans-treated patients with atrial fibrillation? A pilot study

Journal of Thrombosis and Thrombolysis - Proton pump inhibition (PPI) reduces gastrointestinal bleeding on direct oral anticoagulants. However, PPI may affect dabigatran on-treatment levels; and...     

Which is the best choice for gastroesophageal disorders: Melatonin or proton pump inhibitors?

Melatonin is used in many countries to improve sleep disorders. Melatonin is a hormone produced by the pineal gland and enterochromaffin cells which control sleep and gastrointestinal motility. Low levels of melatonin lead to gastroesophageal reflux disease (GERD). Most of patients with GERD have a sleep disorder. So, low melatonin levels is the main cause of insomnia. Beyond this, it has an inhibitory action on gastric acid secretion and seems to control the lower esophageal sphincter. Proton pump inhibitors (PPIs) are a group of drugs whose main action is a pronounced and long-lasting reduction of gastric acid production. They are the most potent inhibitors of acid secretion available today. Omeprazole (one of the PPIs) and melatonin have similarities in their chemical structures. Therefore, we could consider omeprazole as a rough copy of melatonin. In this paper, we compare the advantages and disadvantages of the clinical use of melatonin and PPIs.     

Inhibition of the antithrombotic effects of clopidogrel by proton pump inhibitors: Facts or fancies?

Clopidogrel plus aspirin is considered the antiplatelet treatment of choice in patients with acute coronary syndrome, whether or not they are undergoing a percutaneous coronary intervention (PCI). The same treatment is mandatory in all patients undergoing a PCI with stent implantation. Clopidogrel is a pro-drug that needs metabolic activation through a cytochrome P450-dependent pathway, with an extensive involvement of the CYP 2C19 isoenzyme. Proton pump inhibitors (PPIs) reduce the risk of gastrointestinal bleeding in patients receiving dual antiplatelet therapy. In the past two years some scientific evidences have suggested a possible negative interference of PPIs on antiplatelet effect of clopidogrel because of the competitive inhibition of the CYP 2C19 isoenzyme. Few studies testing platelet reactivity in patients receiving both clopidogrel and a PPI have demonstrated a reduced inhibitory effect of the association on platelet aggregation. Moreover, results from retrospective observational studies have shown a higher incidence of major cardiovascular events in patients receiving both clopidogrel and PPIs. These data have not been confirmed neither by the only prospective randomized study comparing clopidogrel plus omeprazole with clopidogrel alone, nor by the retrospective analysis of the TRITON TIMI 38 trial, where PPIs did not affect the clinical outcome of patients given clopidogrel or prasugrel. Nevertheless both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) have discouraged the concomitant use of clopidogrel and PPIs. Important questions concerning a true interference between the two classes of drugs still remain unanswered and need to be addressed by adequately powered studies.