NSAID-related Ulcers Research Articles

Is the new potent acid-inhibitory drug vonoprazan effective for healing idiopathic peptic ulcers? A multicenter observational study in Akita Prefecture, Japan.

The incidence of peptic ulcers unrelated to H. pylori infection and non-steroidal anti-inflammatory drugs (NSAIDs), termed idiopathic peptic ulcers (IPUs), has increased worldwide. We recently reported that IPUs were refractory to proton pump inhibitor (PPI) treatment. Vonoprazan, which was recently developed in Japan, has shown a more potent acid-inhibitory effect than ordinary PPIs. In the present study, we compared the healing rates among peptic ulcers of different etiologies following treatment with vonoprazan. A multicenter observational study was performed at six participating hospitals in Akita Prefecture, Japan. Consecutive patients who had endoscopically confirmed gastro-duodenal ulcers were enrolled between August 2016 and March 2018. For each patient, the Helicobacter pylori infection status and NSAID use, including aspirin, were checked, and 20mg vonoprazan was administered for 6weeks for duodenal ulcers and 8weeks for gastric ulcers. The healing status was checked by endoscopy at the end of vonoprazan treatment. Patients were divided into four subgroups according to the H. pylori status and NSAID usage. The proportion of IPUs was 18.2%. A total of 162 patients completed the study protocol. The healing rate of IPUs was marginally lower than that of simple H. pylori-associated ulcers (81.2% vs. 93.5%, P = 0.05). Similarly, the healing rate of NSAID-related ulcers, irrespective of concomitant H. pylori infection, was significantly lower than that of simple H. pylori-associated ulcers. Six- or 8-week vonoprazan treatment still seems to be insufficient for healing IPUs. Longer-term vonoprazan or another treatment option may be required to heal potentially refractory peptic ulcers.

Knowledge and Attitudes of Internal Medicine Trainees' Co-Prescribing Patterns of Gastroprotective Agents in Patients Taking Long-Term Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

The side effect profile of NSAIDs is well-established. For prevention of NSAID-related ulcers, the evidence suggests that misoprostol and PPIs (proton pump inhibitors) are superior to H2RAs (histamine-2-receptor-antagonists). Current guidelines recommend use of the lowest possible NSAID dose, as well as consideration of the patients' gastrointestinal and cardiovascular risk profile.

1110 - Misoprostol for the Healing of Aspirin and Nsaid-Related Small Bowel Ulcers in Obscure Gastro-Intestinal Bleeding (Masters Trial)

1110 - Misoprostol for the Healing of Aspirin and Nsaid-Related Small Bowel Ulcers in Obscure Gastro-Intestinal Bleeding (Masters Trial)

Helicobacter pylori and Nonsteroidal Antiinflammatory Drug Peptic Ulcers

Peptic ulcers are defects or breaks in the gastric or small intestinal mucosa that have depth and extend through the muscularis mucosae. The pathogenesis of peptic ulcers is multifactorial and arises from an imbalance of protective and aggressive factors such as when gastrointestinal mucosal defence mechanisms are impaired in the presence of gastric acid and pepsin. Infection with Helicobacter pylori and the use of nonsteroidal anti-inflammatory drugs and acetylsalicylic acid are major risk factors associated with peptic ulcers. In general, these factors disrupt normal mucosal defenses and repair, making the mucosa more susceptible to acid. This review covers the epidemiology of peptic ulcers, diagnostic tests for H. pylori, and treatment of peptic ulcers and H. pylori. The figure shows gastric biopsy samples stained with hematoxylin and eosin demonstrating chronic active gastritis both with and without the presence of H. pylori organisms. The tables list diagnostic tests for H pylori, and common treatment regimens for H. pylori. Key words: Helicobacter pylori, H. pylori, NSAID-related peptic ulcer, diagnosis of helicobacter pylori, H. pylori treatment, urea breath test, ASA after bleeding ulcer This review contains 1 highly rendered figure, 2 tables, and 54 references

Evidence-based clinical practice guidelines for peptic ulcer disease 2015.

The Japanese Society of Gastroenterology (JSGE) revised the evidence-based clinical practice guidelines for peptic ulcer disease in 2014 and has created an English version. The revised guidelines consist of seven items: bleeding gastric and duodenal ulcers, Helicobacter pylori (H. pylori) eradication therapy, non-eradication therapy, drug-induced ulcer, non-H. pylori, non-nonsteroidal anti-inflammatory drug (NSAID) ulcer, surgical treatment, and conservative therapy for perforation and stenosis. Ninety clinical questions (CQs) were developed, and a literature search was performed for the CQs using the Medline, Cochrane, and Igaku Chuo Zasshi databases between 1983 and June 2012. The guideline was developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Therapy is initially provided for ulcer complications. Perforation or stenosis is treated with surgery or conservatively. Ulcer bleeding is first treated by endoscopic hemostasis. If it fails, surgery or interventional radiology is chosen. Second, medical therapy is provided. In cases of NSAID-related ulcers, use of NSAIDs is stopped, and anti-ulcer therapy is provided. If NSAID use must continue, the ulcer is treated with a proton pump inhibitor (PPI) or prostaglandin analog. In cases with no NSAID use, H. pylori-positive patients receive eradication and anti-ulcer therapy. If first-line eradication therapy fails, second-line therapy is given. In cases of non-H. pylori, non-NSAID ulcers or H. pylori-positive patients with no indication for eradication therapy, non-eradication therapy is provided. The first choice is PPI therapy, and the second choice is histamine 2-receptor antagonist therapy. After initial therapy, maintenance therapy is provided to prevent ulcer relapse.

Nonsteroidal Anti-inflammatory Drug and Aspirin-induced Peptic Ulcer Disease

Despite decreasing Helicobacter pylori prevalence, the prevalence of peptic ulcer disease is increasing in the aged population, mainly due to increasing use of NSAIDs to manage pain and inflammation. In addition, low dose aspirin is employed as an anti-coagulant for those who have suffered or are at high risk of ischemic stroke and cardiovascular disease. However, NSAIDs and aspirin are injurious to mucosa of stomach and duodenum. NSAID-induced inhibition of mucosal prostaglandin synthesis is thought to be a major mechanism of gastrointestinal mucosal injury. The proportion of elderly has increased rapidly in Korea, with the proportion over 65 years old expected to be 24.3% in 2030. In this higher-risk population, the strategy to reduce the incidence of NSAID-related peptic ulcers and complications such as bleeding, obstruction and perforation is very important. Proton pump inhibitors (PPIs) with cyclooxygenase-2 inhibitor can be used for reducing the risk of NSAID-related ulcers and upper gastrointestinal (GI) complications. However, continuous use of PPI has several problems. In addition, NSAID-related problems in the lower GI tract have increased, in contrast to the decrease of NSAID-related upper GI disease. The aim of this review is to provide an evidence-based knowledge regarding the mechanism, complications of treatment, and prevention strategies for NSAID- or aspirin-related peptic ulcer disease in Korea.

75-Year-Old Man With Abdominal Pain and Reflux

75-Year-Old Man With Abdominal Pain and Reflux

Risk and preventive factors of low‐dose aspirin‐induced gastroduodenal injuries: A comprehensive review

The risk of peptic ulcer complications, particularly bleeding, is increased in association with the use of low-dose aspirin (LDA). Risk factors for upper gastrointestinal (GI) ulcer or bleeding among LDA users include a history of prior GI events, older age, chronic renal failure, combined antithrombotic therapy and nonsteroidal anti-inflammatory drugs (NSAIDs). Helicobacter pylori and aspirin seem to be independent risk factors for peptic ulcer and bleeding. The studies report conflicting findings about the effect of H. pylori infection on NSAID-related ulcers, and proton-pump inhibitors (PPIs) seem to be superior to eradication only to prevent recurrent ulcer bleeding with LDA. Previous studies indicate that hypoacidity related to corpus atrophy, as well as taking PPIs and co-treatment with angiotensin type 1 receptor blockers (ARBs) and statins seem to reduce peptic ulcer among LDA users. In addition, the interleukin-1β (IL-1β)-511 T allele and angiotensinogen (AGT)-20 CC, which work as the high-producer allele of IL-1β and AGT, are significantly associated with ulcer or ulcer bleeding. The SLCO1B1*1b haplotype, which has the highest transport activity, may diminish the preventive effect of statins or ARBs. The data are still lacking and further prospective studies are needed to identify the specific risk or protective factors for upper GI ulcer and its complications associated with LDA.

Expressions of MMPs and TIMP-1 in Gastric Ulcers May DifferentiateH. pylori-Infected from NSAID-Related Ulcers

Background. Two major causes of gastric ulcers are Helicobacter pylori (H. pylori) infection and nonsteroidal anti-inflammatory drug (NSAID) use. Aims. This study aimed to determine if there were different expressions of matrix metalloproteinases (MMPs) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) between H. pylori-infected and NSAID-related ulcers. Methods. The 126 gastric ulcer patients (H. pylori infected n = 46; NSAID related n = 30; combined with two factors n = 50) provided ulcer and nonulcer tissues for assessment of MMP-3, -7, and -9 and TIMP-1 expression by immunohistochemical staining. Results. Gastric ulcer tissues had significantly higher MMP-3, -7, and -9 and TIMP-1 expressions than nonulcer tissues (P < 0.05). H. pylori-infected gastric ulcers had even higher MMP-7, MMP-9, and TIMP-1 expressions in epithelial cells than NSAID-related gastric ulcers (P < 0.05). In patients with the two combined factors, gastric ulcers expressed similar proportions of antral ulcers and MMP-7 and MMP-9 intensities to NSAID-related gastric ulcers, but lower MMP-9 and TIMP-1 than H. pylori-infected gastric ulcers (P < 0.05). Conclusions. H. pylori-infected gastric ulcers express higher MMP-7, MMP-9, and TIMP-1 than NSAID-related ulcers. In patients with the two combined factors, ulcer location and MMP-7 and MMP-9 intensities are similar to NSAID use.

Gastrocolic Fistula Related to NSAID-Related Gastric Ulcer

Gastrocolic Fistula Related to NSAID-Related Gastric Ulcer

Guidelines for Prevention of NSAID-Related Ulcer Complications

Guidelines for Prevention of NSAID-Related Ulcer Complications

Guidelines for Prevention of NSAID-Related Ulcer Complications

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.

Management of NSAID-Induced Gastrointestinal Toxicity

The association between NSAIDs and the presence of upper gastrointestinal (GI) complications is well established. Evidence that acid aggravates NSAID-induced injury provides a rationale for minimizing such damage by acid suppression. Proton pump inhibitors (PPIs) appear to be very effective in treating NSAID-related dyspepsia, and also in healing gastric and duodenal ulcers in patients continuing to receive the NSAID. An analysis of data from comparative studies of PPIs versus ranitidine, misoprostol and sucralfate shows a therapeutic advantage in favour of the PPI. Several studies now confirm the efficacy of co-therapy with PPIs in the short- and long-term prevention of NSAID-induced upper GI injury. PPIs are more effective than histamine H(2)-receptor antagonists at standard dosages in reducing the risk of gastric and duodenal ulcer, and are superior to misoprostol in preventing duodenal but not gastric lesions. However, when balancing effectiveness and tolerance, PPIs may be considered the treatment of choice in the short- and long-term prevention of NSAID-related mucosal lesions. To date, there are only a few published articles dealing with the role of PPIs in the prevention of upper GI complications. Recent epidemiological and interventional studies provide some evidence that PPIs are of benefit. However, more controlled studies using clinical outcomes are needed to establish the best management strategy (PPIs combined with traditional NSAIDs or with cyclo-oxygenase-2 selective inhibitors) especially in patients with multiple risk factors, in patients using concomitant low-dose aspirin, corticosteroids or anticoagulants (high risk group), or in patients with a history of ulcer complications (very high risk group). Furthermore, it should be underlined that Helicobacter pylori infection positively interacts with the gastroprotective effect of PPIs; therefore, the true efficacy of these drugs in preventing NSAID-related ulcer complications should be reassessed without the confounding influence of this microorganism.

Chronic longitudinal NSAID-related ulcer of the colon (“colon single-stripe sign”) in Munchhausen syndrome

A 62-year-old woman presented with chronic gastrointestinal bleeding. Colonoscopy showed a longitudinal ulcer extending from the ascending to the transverse colon ([Fig. 1 ] a). Biopsies taken from the ulcer ruled out malignancy and inflammatory bowel disease. Despite extensive diagnostic workup, including angiography and CT scan, the cause of the ulcer remained unclear. The patient denied taking nonsteroidal anti-inflammatory drugs (NSAIDs). The patient received empiric treatment with antibiotics, steroids, and mesalamine (5-aminosalicylic acid, 5-ASA), but the ulcer persisted for 6 months on repeated endoscopy. During this period the patient required the transfusion of 17 units of red blood cells. Repeated gastrointestinal hemorrhage finally prompted right hemicolectomy.

Prevention of NSAID-induced ulcers

Cyclooxygenase-2 (COX-2) selective inhibitors were developed as gastrointestinal (GI) safer alternatives to nonselective NSAIDs--providing equivalent analgesic and anti-inflammatory efficacy. Their GI sparing is impaired by concomitant aspirin use, and concerns regarding adverse cardiovascular effects have emerged. Risk factors for NSAID-related complications include a history of ulcer disease or bleeding, concomitant corticosteroid or anticoagulant therapy, use of high-dose or multiple NSAIDs (including low-dose aspirin), advanced age, and certain chronic diseases. If an NSAID must be used in a patient at risk, the lowest-risk NSAID should be used with, in many cases, cotherapy to reduce the risk for ulcers. COX-2 drugs have been associated with a significantly higher risk of vascular events than placebo or naproxen. This increase may be shared by nonselective NSAIDs and appears to be medication- and dose-dependent. Prostaglandin depletion is a central mechanism for NSAID ulcer development, and replacement therapy with misoprostol reduces NSAID toxicity; however, it is rarely used due to side effects. The acid suppression provided by traditional doses of histamine 2-receptor antagonists (H(2)RAs) does not prevent most NSAID-related gastric ulcers. Despite a single study demonstrating that H(2)RAs at double the dose may be effective, studies comparing such high doses with misoprostol or proton pump inhibitors (PPIs) for preventing NSAID ulcers are not available. PPIs are effective at single daily doses, do not demonstrate tachyphylaxis, and are superior to H(2)RAs and misoprostol in reducing ulcers and NSAID-associated dyspepsia. NSAID choice should be predicated by an assessment of an individual's cardiovascular and GI risk. For those with competing cardiovascular and GI risks, the tradeoffs between reducing adverse GI events (COX-2 inhibitor instead of a nonselective NSAID) must be explicitly weighed against concerns about cardiovascular side effects (naproxen instead of other agents). Considering cost is appropriate because it may not be feasible to recommend the "safest" regimen in every circumstance. The cost effectiveness of risk-reducing therapies is intimately tied to the patient's underlying risk. For those at highest GI risk, using a PPI and a low-dose COX-2 inhibitor seems appropriate for those without high cardiovascular risk. For patients whose cardiovascular risk parallels or exceeds GI concerns, naproxen with a PPI is recommended when non-NSAID approaches fail.

Serious NSAID-related GI ulcer complications* are associated with direct annual costs of more than euro42 750 000 in The Netherlands,

Serious NSAID-related GI ulcer complications* are associated with direct annual costs of more than euro42 750 000 in The Netherlands,

Serious NSAID-related GI ulcer complications* are associated with direct annual costs of more than euro42 750 000 in The Netherlands,

Serious NSAID-related GI ulcer complications* are associated with direct annual costs of more than euro42 750 000 in The Netherlands,

Serious NSAID-related GI ulcer complications* are associated with direct annual costs of more than euro42 750 000 in The Netherlands,

Serious NSAID-related GI ulcer complications* are associated with direct annual costs of more than euro42 750 000 in The Netherlands,

A “remarkable” proportion of patients with NSAID-related gastroduodenal ulcers do not receive adequate gastroprotection,

A “remarkable” proportion of patients with NSAID-related gastroduodenal ulcers do not receive adequate gastroprotection,

Under-utilization of gastroprotective drugs in patients with NSAID-related ulcers

To determine the proportion of patients with a risk of NSAID gastropathy receiving adequate gastroprotection. This observational study was performed between November 2001 and December 2003. We selected patients who were hospitalized with perforated and bleeding gastroduodenal ulcers attributable to NSAID use and controls without ulcers. Data were collected on their sociodemographic characteristics, actual and recent medication, comorbidity and medical history. For each patient and control the number of different risk factors associated with NSAID gastropathy was calculated. A composite risk factor (CRF) was obtained from the sum of all separate risk factors. During the observational period a total of 388 patients using NSAID were included in the study, 104 patient cases and 284 matched community-based controls. The mean CRF was significantly higher in patient cases than in controls (cases mean CRF 3.31 (SD 1.67) and controls mean CRF 2.76 (SD 1.45), p = 0.002). A total of 148 (38%) patients used an adequate preventive strategy. Significant variables for using a preventive strategy were concomitant use of steroids (corrected odds ratio 4.22, 95% CI 2.11 8.47, p < 0.001), a history of gastroduodenal ulcers (corrected odds ratio 2.90, 95% CI 1.51 - 5.56, p = 0.001) and concomitant use of low-dose aspirin (corrected odds ratio 1.96,95% CI 1.18 3.25, p= 0.01). Among patients with 4 or more risk factors associated with NSAID gastropathy, 47% still did not use adequate gastroprotection. Gastroprotective drugs are greatly under-utilized in patients with a risk of NSAID gastropathy.