misoprostol and Helicobacter-Infections

Around 17 million items for non-steroidal anti-inflammatory drugs (NSAIDs) are prescribed annually in England alone.1 These drugs are associated with upper gastrointestinal complications.2 For example, each year, NSAIDs cause about 3,500 hospitalisations for, and 400 deaths from, ulcer bleeding in people aged 60 years or above.3 Aspirin, even in low doses, is also associated with gastrointestinal complications.4 5 Here we assess strategies for reducing gastrointestinal complications induced by NSAIDs, including aspirin and selective inhibitors of cyclo-oxygenase-2 (coxibs).

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Cyclooxygenase Inhibitors; Drug Therapy, Combination; Gastrointestinal Diseases; Helicobacter Infections; Helicobacter pylori; Humans; Misoprostol; Proton Pump Inhibitors; Risk Factors

Aspirin is widely used for the prevention of thrombotic cardiovascular disease. The effect of platelet antiaggregation is achieved with low doses of 75-325 mg/day. Due to COX-1 inhibition, associated gastrointestinal adverse effects can occur. Other drugs whose platelet antiaggregant effect is achieved through different mechanisms of action have been developed, such as clopidogrel and ticlopidine, which do not inhibit COX-1. The proportion of patients taking low-dose aspirin alone or in combination with other antiaggregants is high and consequently the use of these drugs should be optimized by reducing their gastrointestinal adverse effects to a minimum. Knowledge of the risk factors that increase the risk of gastrointestinal adverse effects with platelet antiaggregants, such as age, concomitant use of other drugs such as anticoagulants or non-steroidal anti-inflammatory drugs, a history of peptic ulcer -whether complicated or uncomplicated-, and Helicobacter pylori infection, would help to allow management to be individually tailored to each patient. The use of proton pump inhibitors and/or H. pylori eradication should allow a positive balance, even in patients with gastrointestinal risk factors.

Topics: Age Factors; Aged; Aged, 80 and over; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Clopidogrel; Cyclooxygenase 1; Cyclooxygenase Inhibitors; Dinoprostone; Gastrointestinal Hemorrhage; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Middle Aged; Misoprostol; Peptic Ulcer Hemorrhage; Platelet Aggregation Inhibitors; Proton Pump Inhibitors; Risk Factors; Thromboxanes; Ticlopidine

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed but can have serious gastrointestinal (GI) and cardiovascular side effects, which have led to the withdrawal of some of these drugs and continuing uncertainty about the best approach to patients requiring NSAID therapy, particularly in those with GI or cardiovascular risk factors. To define the risks to the GI and cardiovascular systems associated with NSAID therapy, we have undertaken a series of systematic reviews of original articles published between January 1995 and December 2006. In this article we describe the mechanisms and patterns of GI and cardiovascular side effects in NSAID-taking patients and identify a range of drug and patient factors that contribute to an increased risk of adverse events. We conclude that NSAID therapy should not be started unless it is essential, and that Helicobacter pylori eradication should be considered in patients at increased GI risk. We discuss the use of gastroprotective agents and provide practical advice to help physicians assess and balance both cardiovascular and GI risks and benefits in their prescribing decisions.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cardiovascular System; Cyclooxygenase 2 Inhibitors; Endoscopy, Gastrointestinal; Gastrointestinal Tract; Helicobacter Infections; Helicobacter pylori; Humans; Misoprostol; Prostaglandin-Endoperoxide Synthases; Proton Pump Inhibitors; Risk Assessment

Gastrointestinal toxicity is a common adverse effect of traditional non-steroidal anti-inflammatory drugs (NSAIDs) and patients at risk should receive prevention therapies. Selective cyclooxygenase-2 (COX-2) inhibitors (coxibs) are safer to the gastrointestinal tract than traditional NSAIDs. Current prevention strategies in patients who need NSAIDs should also take into account the presence of cardiovascular risk factors, as coxibs and probably most traditional NSAIDs increase the incidence of serious cardiovascular events. Patients without risk factors should be treated with traditional NSAIDs, whereas patients at risk may receive cotherapy with a proton pump inhibitor (PPI) or misoprostol, or a coxib alone. However, patients with a previous bleeding ulcer should receive the combination of a coxib plus a PPI, and Helicobacter pylori should be tested for and treated if present. Coxib and NSAID therapy should be prescribed with caution in patients with increased cardiovascular risk and should be prescribed at the lowest possible dose and for the shortest period of time. These patients will probably be treated with low-dose aspirin or other antiplatelet agents, which puts them at increased risk of upper gastrointestinal complications. The risk of gastrointestinal toxicity with combined therapy of aspirin and coxib may be lower than that with traditional NSAIDs plus aspirin, but all these patients may benefit from PPI cotherapy. When the lower gastrointestinal tract is of concern, coxib instead of NSAID therapy should be considered. Coxib therapy has better gastrointestinal tolerance than traditional NSAIDs and PPI therapy is effective both in the treatment and prevention of NSAID-induced dyspepsia and should be considered in patients who develop dyspepsia during NSAID or coxib therapy.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Cyclooxygenase 2 Inhibitors; Drug Combinations; Dyspepsia; Evidence-Based Medicine; Gastrointestinal Diseases; Gastrointestinal Hemorrhage; Helicobacter Infections; Helicobacter pylori; Humans; Middle Aged; Misoprostol; Proton Pump Inhibitors

The incidence of non-steroidal anti-inflammatory drug-related ulcer complications remains high despite the availability of potent anti-ulcer drugs and selective cyclo-oxygenase-2 inhibitors. Non-steroidal anti-inflammatory drug-related ulcer complications can be minimized by prospective assessment of patients' baseline risk, rational choice and use of non-steroidal anti-inflammatory drugs, and selective use of co-therapy strategies with gastroprotectives. Current recommendations regarding strategies using anti-ulcer drugs and cyclo-oxygenase-2 inhibitors for prevention of clinical non-steroidal anti-inflammatory drug upper gastrointestinal events are largely derived from studies using surrogates such as endoscopic ulcers, erosions, and symptoms in low- to average-risk patients. Conclusions based on surrogate and potentially manipulatable end-points are increasingly suspect with regard to applicability to clinical situations. This article reviews the risks associated with non-steroidal anti-inflammatory drugs including aspirin and includes the effect of the patients' baseline risk, and the confounding effects of Helicobacter pylori infection. In addition, uncertainties regarding the clinical efficacy of anti-ulcer drugs and cyclo-oxygenase-2 inhibitors against non-steroidal anti-inflammatory drug-related ulcer complications are put into perspective. We propose management strategies based on the risk category: low risk (absence of risk factors) (least ulcerogenic non-steroidal anti-inflammatory drug at lowest effective dose), moderate risk (one to two risk factors) (as above, plus an antisecretory agent or misoprostol or a cyclo-oxygenase-2 inhibitor), high risk (multiple risk factors or patients using concomitant low-dose aspirin, steroids, or anticoagulants) (cyclo-oxygenase-2 inhibitor alone with steroids, plus misoprostol with warfarin, or plus a proton pump inhibitors or misoprostol with aspirin), and very high risk (history of ulcer complications) (avoid all non-steroidal anti-inflammatory drugs, if possible or a cyclo-oxygenase-2 plus a proton pump inhibitors and/or misoprostol). The presence of H. pylori infection increases the risk of upper gastrointestinal complications in non-steroidal anti-inflammatory drug users by two- to fourfold suggesting that all patients requiring regular non-steroidal anti-inflammatory drug therapy be tested for H. pylori.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Aspirin; Cyclooxygenase 2; Decision Making; Gastrointestinal Diseases; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Isoenzymes; Membrane Proteins; Misoprostol; Prostaglandin-Endoperoxide Synthases; Proton Pump Inhibitors; Risk Assessment; Risk Factors; Stomach Ulcer

Due to the extraordinary high prevalence of peptic lesions in the upper gastrointestine in the long-term treatment with nonsteroidal anti-inflammatory drugs, a prophylaxis in patients belonging to high-risk groups is essential. Misoprostol, proton pump inhibitors and histamine 2-receptor antagonists have been evaluated in prospective studies. The efficacy of Misoprostol is well documented, though its use in prevention is frequently limited due to side effects. Proton pump inhibitors are also well established, especially in the therapy of nonsteroidal anti-inflammatory drugs associated peptic ulcers and in consecutive secondary prevention. The histamine 2-receptor antagonist Famotidine in a high oral dosage is able to reduce the frequency of peptic lesions too, but not to the same degree as Misoprostol and proton pump inhibitors. It is very likely that helicobacter pylori eradication without any further mucosaprotective therapy will only decrease the incidence of upper gastrointestinal bleeding in low dose Aspirin application. In spite of controversial studies this eradication seems to be a useful additional therapy for ulcer prophylaxis in high risk groups. Selective Cyclooxygenase-2 inhibitors may become a promising alternative, from a pathophysiological perspective. However, to date there has been a lack of clear comparative studies with common nonsteroidal anti-inflammatory drugs plus mucosaprotecting agents. Daily therapy costs are higher with a Cyclooxygenase-2 inhibitor than using the traditional nonsteroidal anti-inflammatory drugs together with either proton pump inhibitors, histamine 2-receptor antagonists or Misoprostol--a fact that should be considered in primary therapeutic decisions. In the following review we will present the most important results of the different prophylactic and therapeutic modalities. On the basis of placebo-controlled, prospective studies on the one hand and the recommendations of the scientific societies on the other, a guideline for daily clinical practice will be suggested.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Misoprostol; Peptic Ulcer; Proton Pump Inhibitors

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Amoxicillin; Anti-Inflammatory Agents, Non-Steroidal; Clarithromycin; Drug Therapy, Combination; Evidence-Based Medicine; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Lansoprazole; Misoprostol; Omeprazole; Peptic Ulcer; Proton Pump Inhibitors

Topics: Alprostadil; Anti-Ulcer Agents; Cytokines; Dinoprostone; Drug Therapy, Combination; Enprostil; Helicobacter Infections; Helicobacter pylori; Humans; Misoprostol; Peptic Ulcer; Secondary Prevention

Nonsteroidal anti-inflammatory drugs (NSAIDs) have superseded Helicobacter pylori infection as the most important cause of peptic ulcer bleeding. Eradication of H. pylori in NSAID users will not affect ulcer healing. In high-risk patients with a history of ulcer bleeding, curing H. pylori infection alone without acid suppression has substantially reduced the risk of rebleeding caused by low-dose aspirin but not nonaspirin NSAIDs. In a study comparing the safety profile of misoprostol in combination with NSAID against nabumetone in high-risk patients with a history of ulcer bleeding, both strategies were unable to confer significant protection against the risk of rebleeding.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Aspirin; Butanones; Helicobacter Infections; Helicobacter pylori; Humans; Misoprostol; Nabumetone; Peptic Ulcer Hemorrhage; Secondary Prevention

Two recently reported studies of nonsteroidal anti-inflammatory drugs (NSAIDs), the Omeprazole versus Misoprostol for NSAID-induced Ulcer Management and the Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID-associated Ulcer Treatment studies, concluded that omeprazole was superior to a subtherapeutic misoprostol or an ineffective dose of ranitidine for the endpoint, prevention of gastroduodenal ulcers in chronic NSAID users. Helicobacter pylori status was collected prospectively but was not reported. We report separate analyses for patients with unequivocal NSAID ulcers (H. pylori negative) and patients whose NSAID use was complicated by the presence of an active H. pylori infection. Omeprazole was superior to placebo for the prevention of ulcer recurrence in chronic NSAID users. However, omeprazole was not significantly better than a subtherapeutic dose of misoprostol for the prevention of gastroduodenal ulcers in chronic NSAID users. Misoprostol was superior to omeprazole for the prevention of gastric ulcers among those patients with unequivocal NSAID ulcers (8.2% vs 16.6%, respectively; P <0.05). Omeprazole was not statistically different from misoprostol for gastric ulcer prevention in those whose NSAID use was complicated by an active H. pylori infection. Ranitidine and omeprazole were also not statistically different for the prevention of unequivocal NSAID gastric ulcers (14.6% vs 11.6%, respectively; P = 0.56). That the Misoprostol Ulcer Complications Outcomes Safety Assessment (MUCOSA) trial found full-dose misoprostol to be more effective in ulcer prevention than it was in prevention of ulcer complications suggests that either many of the ulcer complications were related to H. pylori ulcers or that more antisecretory activity than can be provided with misoprostol is needed, or both. The question remains whether the combination of low-dose misoprostol plus an antisecretory drug (either an H(2)-receptor antagonist or a proton pump inhibitor) would provide superior results compared with either alone. That omeprazole was not superior to one half the dose of misoprostol used in the ulcer complication prevention, or MUCOSA, study indicates that it would not be prudent to suggest that ulcer prevention with omeprazole alone would be able to provide similar protection to misoprostol.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Clinical Trials as Topic; Enzyme Inhibitors; Helicobacter Infections; Helicobacter pylori; Humans; Misoprostol; Omeprazole; Peptic Ulcer; Proton Pump Inhibitors; Ranitidine

When considering the diseases of the stomach and duodenum, peptic ulcer disease has been the one of greatest clinical impact. Although there are several components that contribute mechanistically to ulcer disease, it is recognized that gastroduodenal mucosal prostaglandins play a central pathogenic role, especially in ulcers related to the use of NSAIDs. As a result of understanding the mechanisms of NSAID-induced ulceration, the crucial function that gastroduodenal mucosal prostaglandins have in mucosal defense and repair is appreciated. It now is held widely that mucosal prostaglandin deficiency increases susceptibility to ulcer formation and that exogenous administration of supplemental prostaglandins reduces ulcer risk. This article reviews the role that mucosal prostaglandins play in defense of the gastric and duodenal mucosa against injury and ulceration.

Topics: Age Factors; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Duodenal Ulcer; Gastric Mucosa; Helicobacter Infections; Humans; Intestinal Mucosa; Isoenzymes; Membrane Proteins; Misoprostol; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Stomach Ulcer

Our knowledge of the mechanism by which aspirin and traditional NSAIDs work and damage the gastrointestinal mucosa, recently markedly improved, has suggested a number of measures for the prevention of the NSAID-induced GI lesions. Among these, perhaps the most innovative approach seems to be the nitric oxide-releasing NSAIDs or compounds, like amtolmetin guacyl, that work by increasing the endogenous biosynthesis of NO selectively at gastric mucosa level. Further data, stemming from large RCTs and confirming the results of experimental studies and the initial clinical experiences, are needed to better define the true clinical impact of this approach.

Topics: Age Factors; Aged; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Cytoprotection; Duodenal Ulcer; Female; Gastrointestinal Diseases; Glycine; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Intestinal Diseases; Male; Middle Aged; Misoprostol; Pyrroles; Risk Factors; Stomach Ulcer; Sucralfate; Ulcer

The authors review the digestive ulceration risk factors and the criteria for selecting a non steroidal antiinflammatory (NSAI), included the most recent drugs, such as selective anti-cyclo-oxygenases 2. They actualize the preventive strategies and insist on the values of misoprostol and of slow acting anti-rheumatic drugs. In the case of digestive ulcerations, they plead for the immediate stop of the NSAI and its replacement if necessary by corticosteroids, for the prescription of a proton pump inhibitor (PPI) or mesalazine according to the localisation of the lesion, finally for the eradication within 8 days of Helicobacter pylori.

Topics: Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Cyclooxygenase Inhibitors; Drug Interactions; Helicobacter Infections; Helicobacter pylori; Humans; Misoprostol; Peptic Ulcer; Steroids; Sulfasalazine

To integrate the realization that peptic ulcer most commonly reflects infection with Helicobacter pylori or use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) into a disease management approach.. Guidelines were outlined by the author and presented for review to the American College of Gastroenterology (ACG) Practice Parameters Committee, selected by the president of the ACG, and a panel of experts in peptic ulcer, selected by the committee.. These guidelines were formulated following extensive review of the literature obtained by MEDLINE search and presented for detailed review and revision to unpublicized committee meetings on three occasions and to experts by mail. These recommendations are an official statement of the ACG and have been approved by the American Gastroenterological Association and the American Society for Gastroenterological Endoscopy. Firm recommendations are discriminated from reasonable suppositions pending definitive data.. Since cure of H. pylori infection decreases recurrence rates and facilitates healing, antibiotic therapy is indicated for all H. pylori-infected ulcer patients. No optimal, simple antibiotic regimen has yet emerged. Simultaneous conventional ulcer therapy is recommended to facilitate symptom relief and healing. For refractory ulcers, only maximal acid inhibition offers advantage over continued conventional therapy; cure of H. pylori infection is likely to facilitate healing of refractory ulcers. Only with complicated or refractory ulcers should conventional maintenance therapy be continued, at least until successful H. pylori eradication is confirmed. A search for NSAID use is indicated for all ulcer patients. For NSAID-associated ulcers these drugs should be discontinued if possible and H. pylori, if present, should be cured.

Topics: Antacids; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Biopsy; Bismuth; Breath Tests; Contraindications; Drug Therapy, Combination; Dyspepsia; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Metronidazole; Misoprostol; Peptic Ulcer; Predictive Value of Tests; Proton Pump Inhibitors; Recurrence

Despite the progress in the diagnosis and treatment of Helicobacter pylori-related peptic ulcer disease, it has become apparent that we may be in the midst of an epidemic of nonsteroidal anti-inflammatory drug ulcers and ulcer complications. We also have almost no information about whether there is a link between ulcers in NSAID users and H. pylori infection or whether clinically significant interactions occur.. Current data regarding the diagnosis, prevention, and treatment of NSAID-induced ulcers and the possible relationship between H. pylori ulcers and NSAID use is reviewed.. We need to rethink past conclusions about NSAIDs and gastroduodenal complications and also re-do many of the experiments, taking into account the H. pylori status of the patient (infected, uninfected, cured). It is predicted that the epidemic of NSAID complications will only get worse. Only the future will tell whether selective COX II inhibitors or NO-NSAIDs that incorporate a nitroxybutyl moiety will actually provide the same benefit at lower risk. Until then we must rely on more rational use of NSAIDs, and misoprostol to keep the number of complications at a minimum.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Cyclooxygenase Inhibitors; Helicobacter Infections; Helicobacter pylori; Humans; Misoprostol; Peptic Ulcer; Peptic Ulcer Hemorrhage; Peptic Ulcer Perforation; United States

Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective medications and are very commonly prescribed. They are used by a large proportion of elderly persons who are most prone to adverse events. NSAID gastropathy is the commonest side effect. The relative risk of adverse events is high, but the absolute risk for any individual patient is low. Individualizing the risk/benefit ratio would lead to cost effective care.

Topics: Age Factors; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Duodenal Ulcer; Gastric Mucosa; Gastrointestinal Diseases; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Misoprostol; Prostaglandins; Risk Factors; Sex Factors; Stomach Ulcer

Aspirin and nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal bleeding is recognized as an important health problem. We performed a single-center randomized clinical trial to compare the effect of high-dose intravenous proton pump inhibitor (omeprazole) alone (group 1) with omeprazole in combination with a low-dose prostaglandin analog (misoprostol; group 2) on clinical outcomes in patients with aspirin/NSAID-induced upper gastrointestinal bleeding. Additionally, we evaluated the contribution of Helicobacter pylori eradication therapy on the late consequences. Patients were recruited to the study if they had upper gastrointestinal bleeding with history of taking aspirin or other NSAIDs within the week before the onset of bleeding. All were evaluated in terms of probable risk factors. After the standard treatment protocol, patients with histologically proven H pylori infection were prescribed a triple eradication therapy for 14 days. The primary end points were recurrent bleeding, surgery requirement, and death rates before discharge and at the end of follow-up period. This study lasted for 2 years. A total of 249 patients with upper gastrointestinal bleeding were admitted, and 49.7% of these patients were users of aspirin/NSAIDs. There were 67 patients in group 1 and 56 in group 2. The distributions for gender, age, comorbidity, H pylori infection, and high-risk ulcer rate were similar in both groups. Among aspirin/NSAID users, endoscopy revealed duodenal ulcer in 47 (38.2%), gastric ulcer in 10 (8.1%), and erosive gastropathy in 33 (26.8%). The overall rebleeding occurred in 12.2%, death in 2.4% of the patients. The in-hospital death (P=.414), rebleeding (P=.925), and surgery (P=.547) rates were similar in both treatment groups. After the follow-up period of 3 months, overall rebleeding occurred in 4.1%, and death in 4.8% of the patients. The overall mortality rate was highest in those >65 years old, who were chronic low-dose aspirin users with comorbidity. One died of transfusion-related graft-versus-host disease. In this pilot study, we indicated that adding misoprostol (600 microg/day) to standardized proton pump inhibitor treatment did not improve or change the rebleeding or mortality rates of patients with upper gastrointestinal bleeding related to aspirin/NSAID use. Other prospective studies on higher doses of misoprostol are needed to establish the coeffect. One should bear in mind that all blood products must be irradiated befo

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Aged; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Aspirin; Comorbidity; Drug Therapy, Combination; Duodenal Ulcer; Endoscopy, Gastrointestinal; Female; Gastric Mucosa; Gastrointestinal Hemorrhage; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Misoprostol; Omeprazole; Pantoprazole; Pilot Projects; Prospective Studies; Recurrence

Our aim was to investigate the effect of misoprostol on NSAID-induced gastroduodenal mucosal damage in patients with rheumatoid arthritis. The study included 40 patients, and it was designed as a double-blind, placebo-controlled trial. Misoprostol significantly reduced the gastroduodenal mucosal lesions found at endoscopy (P < 0.05) and prevented the development of ulcers. The cumulative incidence of ulcers at four weeks was 5% in the placebo group and 0% in the misoprostol group. The basal and pentagastrin-stimulated acid output as evaluated after 23 days of treatment with misoprostol was not significantly affected. Forty-one percent of the patients had signs of current Helicobacter pylori infection, 33% had positive serology only, and 26% had no evidence of infection. Most of the patients with current infection belonged to blood group O (P < 0.05). Misoprostol treatment did not affect the occurrence of Helicobacter pylori or the rheumatic disease activity. It is concluded that the protective actions of misoprostol on the gastroduodenal mucosa of NSAID-treated patients are largely mediated by mechanisms other than inhibition of acid secretion. The relationship among active Helicobacter pylori infection, blood group O, and peptic ulcer may be helpful to identify a subpopulation of patients taking NSAIDs at risk of developing peptic ulcers.

Topics: ABO Blood-Group System; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Double-Blind Method; Duodenum; Female; Gastric Acid; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Intestinal Mucosa; Male; Middle Aged; Misoprostol; Peptic Ulcer

Topics: Animals; Caspases, Initiator; Helicobacter Infections; Helicobacter pylori; Humans; Inflammasomes; Interleukin-1beta; Macrophages; Mice; Misoprostol; Peptic Ulcer; Pyroptosis

Guidelines for clinical practice are intended to indicate preferred approaches to medical problems as established by scientifically valid research. Double-blind, placebo-controlled studies are preferable, but compassionate use reports and expert review articles are used in a thorough review of the literature conducted through Medline with the National Library of Medicine. Only when data that will not withstand objective scrutiny are available is a recommendation identified as a consensus of experts. Guidelines are applicable to all physicians who address the subject, without regard to specialty training or interests, and are intended to indicate the preferable, but not necessarily the only, acceptable approach to a specific problem. Guidelines are intended to be flexible and must be distinguished from standards of care, which are inflexible and rarely violated. Given the wide range of specifics in any health-care problem, the physician must always choose the course best suited to the individual patient and the variables in existence at the moment of decision. These guidelines were developed under the auspices of the American College of Gastroenterology by a committee of experts in the field, reviewed by its Practice Parameters Committee, and approved by the Board of Trustees. The recommendations of these guidelines are therefore considered valid at the time of production based on the data available. New developments in medical research and practice pertinent to each guideline will be reviewed at an established time and indicated at publication to assure continued validity. Owing to the volume of new data on the subject of non-steroidal anti-inflammatory drug (NSAID)-related injury to the upper gastrointestinal tract, i.e., the advent of cyclooxygenase (COX)-2 inhibitors, new data on interactions between these agents, as well as traditional NSAIDs, with aspirin and H. pylori, it was elected by the Committee to confine these guidelines to upper gastrointestinal (GI) injury and to leave post-duodenal injury as the subject of a separate guideline.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Anticoagulants; Aspirin; Cyclooxygenase 2 Inhibitors; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Misoprostol; Peptic Ulcer; Peptic Ulcer Hemorrhage; Proton Pump Inhibitors; Risk Factors

Peptic ulcer (PU) bleeding is the main cause of non-variceal gastrointestinal bleeding. Negative outcomes include re-bleeding and death, and many of the deaths are associated with decompensation of coexisting medical conditions precipitated by acute bleeding event. Accurate analysis of risk for clinical features can help physician to decide treatment modality. Endoscopy can detect bleeding stigmata and perform therapeutic hemostasis. Proton pump inhibitor (PPI) 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 upper gastrointestinal (UGI) bleeding significantly reduces the proportion of patients with stigmata of recent hemorrhage (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 endoscopic hemostasis for those with major SRH, is likely to be the most cost-effective. The treatment of H. pylori infection was found to be more effective than anti-secretory therapy in preventing recurrent bleeding from PU. H. pylori eradication alone and eradication followed by misoprostol (with switch to PPI, if misoprostol is not tolerated) are the two most cost-effective strategies to prevent ulcer bleeding among H. pylori-infected NSAID users, although the data cannot exclude PPIs also being cost-effective treatment. This review focuses specifically on the current treatment of patients with acute bleeding from a peptic ulcer.

Topics: Anti-Ulcer Agents; Endoscopy, Gastrointestinal; Gastrointestinal Hemorrhage; Helicobacter Infections; Helicobacter pylori; Hemostasis, Endoscopic; Humans; Misoprostol; Peptic Ulcer; Peptic Ulcer Hemorrhage; Proton Pump Inhibitors

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used medications in Korea. Gastrointestinal toxicity, including peptic ulcer, is a common adverse effect of NSAIDs. Risk factors for NSAID-related peptic ulcer include a previous history of peptic ulcer, advanced age, high dose, concomitant use of corticosteroids, anticoagulants, other NSAIDs including low-dose aspirin. Preventive measure(s), such as COX-2 inhibitor, proton pump inhibitor or misoprostrol, should be done for patients requiring NSAID therapy who have high-risk factor(s) for peptic ulcer. Low dose aspirin also increases the risk of peptic ulcer, so preventive measure(s) should be done for high-risk patients. The eradication of Helicobacter pylori is recommended for high-risk NSAID-users. Treatment strategies for peptic ulcers in NSAID users are mostly the same for peptic ulcers in NSAID non-users.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Anticoagulants; Aspirin; Cyclooxygenase 2 Inhibitors; Helicobacter Infections; Helicobacter pylori; Humans; Misoprostol; Peptic Ulcer; Proton Pump Inhibitors

Topics: Age Factors; Aged; Aged, 80 and over; Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Aspirin; Cardiovascular Diseases; Gastric Mucosa; Gastrointestinal Hemorrhage; Helicobacter Infections; Helicobacter pylori; Humans; Meta-Analysis as Topic; Middle Aged; Misoprostol; Peptic Ulcer; Peptic Ulcer Hemorrhage; Platelet Aggregation Inhibitors; Risk Factors

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Cyclooxygenase 2 Inhibitors; Dyspepsia; Female; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Ibuprofen; Middle Aged; Misoprostol; Osteoarthritis; Sucralfate

A past history of peptic ulceration increases the risk of an ulcer developing during non-steroidal anti-inflammatory drug (NSAID) use. Whether this is due to Helicobacter pylori infection or to reactivation of the original lesion is unclear.. We used multivariate regression analyses of three large similar trials to identify factors that placed patients at high risk of ulcer development or relapse. We compared the efficacy of omeprazole 20 mg daily, misoprostol 200 micro g twice daily, and ranitidine 150 mg twice daily in preventing ulcers and erosions at different sites and in patients who were H pylori positive and negative.. Patients with endoscopic lesions (which healed) initially were significantly more likely than those without to develop further erosions or ulcers during treatment (rate ratio 2.12, 1.07-4.17). Risk mounted further with ulcers versus erosions, particularly those that had been slow to heal. There was a highly significant tendency for the relapse lesion to replicate the site and type of the original lesion (mean odds ratios ranging from 3 to 14). Treatment failure was significantly less likely with omeprazole than with placebo, misoprostol, or ranitidine. This advantage was especially evident in H pylori positive patients receiving acid suppression (5.7% v 16.6% for gastric ulcer with omeprazole).. Relapse of lesions in patients taking NSAIDs was highly site and type specific and not adversely affected by H pylori status. This strongly implies that local mucosal factors predispose to ulcer development in patients taking NSAIDs. Identification of the responsible mucosal changes would aid understanding and could promote better treatment.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Cohort Studies; Duodenal Ulcer; Female; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Misoprostol; Multivariate Analysis; Omeprazole; Ranitidine; Recurrence; Risk Factors; Stomach Ulcer; Treatment Failure

Factors predisposing to endoscopic ulcer formation or healing with non-steroidal anti-inflammatory drugs (NSAIDs) have not been well defined.. We used multivariate analysis of data from three large similar trials to identify factors associated with endoscopic lesions and healing. We compared the effectiveness of omeprazole 20 mg and 40 mg daily, misoprostol 200 micro g four times daily, and ranitidine 150 mg twice daily in healing ulcers and erosions at different sites and in patients who were Helicobacter pylori positive and negative.. Older age, past ulcer history, rheumatoid arthritis, and H pylori infection were significantly associated with ulcers. Duodenal ulcer was significantly more likely than gastric ulcer with a past ulcer history (odds ratio 1.59, 1.16-2.17), H pylori infection (1.4, 1.04-1.92), and male sex (2.35, 1.75-3.16) while female sex, older age (> or = 60 years: 1.39, 1.03-1.88), and higher NSAID dose (>1 defined daily dose: 1.57, 1.16-2.14) were associated with gastric ulceration. Sex differences were seen in both H pylori positive and negative patients. Gastric and duodenal ulcer healing was significantly faster with omeprazole 20 mg than with misoprostol 200 micro g four times daily or ranitidine 150 mg twice daily although misoprostol was more effective at healing erosions. Gastric ulcer healing was slower with large ulcers (0.37, 0.25-0.54 for >10 mm v 5-10 mm) or a past ulcer history (0.51, 0.34-0.76), and faster with H pylori infection (1.55, 1.06-2.29), especially with acid suppression (72% v 37% at four weeks with ranitidine).. Among NSAID users, H pylori and male sex independently increase the likelihood of duodenal ulceration. H pylori infection does not affect duodenal ulcer healing and enhances gastric ulcer healing by ranitidine and possibly other acid suppressing treatments.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Disease Susceptibility; Duodenal Ulcer; Endoscopy, Digestive System; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Misoprostol; Multivariate Analysis; Omeprazole; Ranitidine; Sex Factors; Stomach Ulcer; Treatment Outcome; Wound Healing

Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of clinical upper gastrointestinal tract (UGI) events, namely, symptomatic ulcer, perforation, bleeding, and obstruction. Our objective in this study was to compare the cost-effectiveness of several strategies aimed at reducing the risk of clinical UGI events in NSAID users.. A decision tree model was used for patients requiring long-term treatment with NSAIDs to compare conventional NSAID therapy alone with 7 other treatment strategies to reduce the risk of NSAID-related clinical UGI events (cotherapy with proton-pump inhibitor, cotherapy with misoprostol, cyclooxygenase [COX]-2-selective NSAID therapy, or Helicobacter pylori treatment followed by each of the previous strategies, including conventional NSAID treatment, respectively). The outcome measure is the incremental cost per clinical UGI event prevented compared with conventional NSAID treatment over 1 year.. The use of a COX-2-selective NSAID and cotherapy with proton-pump inhibitors were the 2 most cost-effective strategies. However, the incremental cost associated with these strategies was high (>$35 000) in persons with a low risk of clinical UGI event with conventional NSAIDs (eg, 2.5% per year). If the baseline risk of clinical UGI events is moderately high (eg, 6.5%), using a COX-2-selective NSAID becomes the most effective and least costly (dominant) treatment strategy, followed closely by cotherapy with a daily proton-pump inhibitor. Because small changes in costs or assumed efficacy of these drugs could change the conclusions, the incremental cost-effectiveness ratios between any 2 strategies were presented in a nomogram that allows the flexible use of a wide range of values for costs and rates of clinical UGI events.. The risk of clinical UGI events in NSAID users depends on their baseline risk, the added risk associated with the individual NSAID, and the protection conferred by cotherapy. A nomogram can be used to incorporate these factors and derive estimates regarding cost-effectiveness of competing strategies aimed at reducing the risk of clinical UGI events.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Cost-Benefit Analysis; Decision Support Techniques; Drug Costs; Health Care Costs; Helicobacter Infections; Humans; Misoprostol; Peptic Ulcer; Peptic Ulcer Hemorrhage; Peptic Ulcer Perforation; Primary Prevention; Proton Pump Inhibitors; Risk Assessment; Risk Factors; United States

The recently reported OMNIUM and ASTRONAUT NSAID ulcer prevention trials using omeprazole to prevent endoscopic ulcer recurrence among chronic NSAID users suggested superiority over misoprostol or ranitidine.. To test the hypothesis the results from the OMNIUM and ASTRONAUT studies would not be generalizible as ulcer healing and ulcer recurrence would differ in relation to Helicobacter pylori status.. The data regarding H. pylori status were made available by AstraZenca allowing separate analysis of the outcome of those with NSAID ulcers (i.e. without H. pylori infection) and those NSAID use was complicated with the presence of an active H. pylori infection.. Reanalysis confirmed that omeprazole was superior to placebo for the prevention of ulcer recurrence in chronic NSAID users. However, overall omeprazole was not significantly better than the subtherapeutic dose (400 microg/day) of misoprostol (14.5% vs. 19.6%, respectively, p =.93); 400 microg of misoprostol was actually superior to omeprazole for the prevention of gastric ulcers among those NSAID ulcers (8.2% vs. 16.6% for misoprostol and omeprazole, respectively; p <.05). Omeprazole was also not statistically different from misoprostol for gastric ulcer prevention in those whose NSAID use was complicated by an active H. pylori infection. Omeprazole was not significantly different from 300 mg of ranitidine for the prevention of NSAID gastric ulcers (14.6% vs. 11.6%, respectively, p =.56). Duodenal ulcers were over represented among H. pylori infected NSAID users and duodenal ulcer prevention was more sensitive to acid suppression than gastric ulcer.. The OMNIUM and ASTRONAUT trials may have provided an unrealistic sense of security regarding the effectiveness of omeprazole for protection against ulcer recurrence in chronic NSAID users.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Clinical Trials as Topic; Helicobacter Infections; Helicobacter pylori; Humans; Misoprostol; Omeprazole; Peptic Ulcer; Ranitidine; Recurrence; Treatment Outcome

Use of low-dose aspirin is associated with gastroduodenal mucosal damage and increased risk of upper gastrointestinal (GI) bleeding. Many patients on low-dose aspirin should receive prophylactic treatment, because they often present several risk factors that may lead to upper GI complications in nonsteroidal anti-inflammatory drug (NSAID) users. It is reasonable to assume that effective therapy (e.g., omeprazole, misoprostol, and high-dose famotidine) in the prevention of NSAID-induced gastroduodenal ulcers will also be effective in this setting. However, the best therapeutic approach to reducing GI toxicity in low-dose aspirin users is not defined, because only a few studies have focused on this problem. Omeprazole seems very effective in reducing both acute gastroduodenal mucosal damage and upper GI bleeding in the high-risk patient taking low-dose aspirin, but data with other antiulcer agents are lacking (misoprostol) or inconsistent (ranitidine) at present. No data are available on the effect of these drugs on dyspepsia or chronic gastroduodenal ulcers in the long-term use of low-dose aspirin. The role of Helicobacter pylori is controversial, but it may increase mucosal damage and the risk of upper GI bleeding in these patients. More data are needed to define the best therapeutic regimen in patients taking low-dose aspirin.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Aspirin; Gastrointestinal Hemorrhage; Helicobacter Infections; Helicobacter pylori; Humans; Lansoprazole; Misoprostol; Omeprazole; Peptic Ulcer; Ranitidine

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Cost-Benefit Analysis; Drug Therapy, Combination; Enzyme Inhibitors; Helicobacter Infections; Helicobacter pylori; Humans; Misoprostol; Omeprazole; Stomach Diseases

Topics: Adult; Amoxicillin; Anti-Ulcer Agents; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Misoprostol; Omeprazole; Penicillins; Pilot Projects

Topics: Amoxicillin; Antacids; Anti-Bacterial Agents; Anti-Ulcer Agents; Clarithromycin; Diarrhea; Drug Interactions; Drug Resistance, Microbial; Duodenal Ulcer; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Metronidazole; Misoprostol; Peptic Ulcer; Proton Pump Inhibitors; Salicylates; Salicylic Acid; Sucralfate; Tetracycline

Prostaglandins are widely used in the prevention and healing of non-steroidal anti-inflammatory drug (NSAID) induced gastric and duodenal ulcers, but their longterm effect on the human gastric mucosa is unknown. This study assessed the effect of coadministration of prostaglandins with NSAIDs on the histology of the gastroduodenal mucosa. Histological appearances (using the Sydney system) of gastric biopsy specimens from 180 patients receiving longterm NSAID treatment of whom 90 had been receiving misoprostol (400-800 micrograms/day) for one to two years were studied. Both groups of patients were comparable with regard to clinical and demographic details. There was no significant difference (p > 0.1) in the prevalence of chronic gastritis (total, corpus or antrum only) between patients receiving (36 of 90 (40%)) or not receiving misoprostol (35 of 90 (39%)). Chronic gastritis was equally associated with the presence of Helicobacter pylori, 86% and 73% (p > 0.1), respectively, in the two groups. Significantly fewer patients receiving misoprostol had reactive gastritis than those receiving only NSAIDs (8 (9%) versus 27 (30%), p < 0.01). Reactive gastritis was not associated with H pylori. Thirty nine (43%) of the misoprostol treated patients had normal histology compared with 16 (18%) receiving only NSAIDs (p < 0.01). These results show two different patterns of gastric damage in patients receiving NSAIDs, namely chronic and reactive gastritis. Misoprostol treatment was associated with a significantly reduced prevalence of reactive gastritis and it is suggested that this, along with its antisecretory action, may explain the reduced prevalence of gastroduodenal lesions when coadministered with NSAIDs.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Arthritis; Drug Therapy, Combination; Female; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Misoprostol; Time Factors

Topics: Antacids; Anti-Bacterial Agents; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Misoprostol; Omeprazole; Peptic Ulcer; Sucralfate