Effects of Helicobacter pylori and nonsteroidal anti-inflammatory drugs on peptic ulcer disease: a systematic review.

BACKGROUND & AIMS: The aim was to systematically review the interactions between Helicobacter pylori (HP) infection and NSAID use on the risk of uncomplicated or bleeding peptic ulcer. METHODS: All relevant full articles published in MEDLINE from January 1989-June 2004 were included. Sensitivity analyses for type of controls or use of aspirin or non-aspirin NSAIDs were performed. RESULTS: In 21 studies involving 10,146 patients, uncomplicated peptic ulcer was more common in HP-positive than HP-negative patients (pooled odds ratio [OR], 2.17) or in HP-positive than HP-negative NSAID users (OR, 1.81). In 6 age-matched controlled studies, ulcer was more common in HP-positive than HP-negative patients (OR, 4.03), irrespective of NSAID use, and in NSAID users than non-users (OR, 3.10), irrespective of HP status; the risk of ulcer was 17.54-fold higher in HP-positive NSAID users than HP-negative non-users. The use of aspirin or non-aspirin NSAIDs did not affect the results. Ulcer bleeding was evaluated in 17 studies involving 4084 patients. NSAID use was more frequent in bleeding patients than control subjects (OR, 5.13), irrespective of HP status and type of controls. In contrast, HP infection in bleeding patients compared with control subjects was less frequent in the 8 studies with ulcer cases as control subjects (OR, 0.40) and more frequent in the 9 studies with uninvestigated subjects as controls (OR, 2.56). In the latter studies, presence compared with the absence of both HP and NSAIDs increased the risk of bleeding 20.83-fold. CONCLUSION: HP infection and NSAID use represent independent and synergistic risk factors for uncomplicated and bleeding peptic ulcer.     

Role of Helicobacter pylori Infection on Upper Gastrointestinal Bleeding in the Elderly (A Case-Control Study)

Nonsteroidal antiinflammatory drug (NSAID) useis known to be associated with a high incidence of uppergastrointestinal tract bleeding in the elderly. Theincreased prevalence of Helicobacter pylori (HP) infection, which also occurs with age, suggeststhat an interaction between NSAID use and HP infectionmay explain the higher incidence of ulcer complicationsin the elderly. The aim of the present study was to determine if a relationship existsbetween HP infection and NSAID use in elderly patientswith upper gastrointestinal bleeding. This was a case-control study on 146 elderly patients (73/group). The bleeding group consisted of 37 males and 36females (mean age 80.4 years, range 70-96) with symptoms(hematemesis, melena, anemia with loss of more than 3 ghemoglobin), and endoscopic stigmata of bleeding. The control group consisted of 73 age- andsex-matched patients with the same endoscopic diagnosisbut with no endoscopic stigmata of bleeding. NSAID usewas evaluated by interview at the time of endoscopy, and HP infection was confirmed in all cases byhistology and the rapid urease test. Statisticalanalyses were performed using the chisquare test andlogistic regression. In both groups, 46.57% of patients were affected with gastric ulcer, 36.98% withduodenal ulcer, and 16.43% with erosive gastritis. Thebleeding group had a significantly higher percentage ofNSAID users (53.42% vs 19.17%, P < 0.0001) and a lower percentage of HP-positive patients(47.94% vs 72.60%, P = 0.004). The NSAID use pattern wasas follows: occasional users (sporadic, as needed duringthe previous week): 53.8% of bleeding cases and 50% of controls; acute users (continuoustherapy for less than one month): 17.9% of bleedingcases and 28.5% of controls; and chronic users(continuous therapy for more than one month): 28.2% ofbleeding cases and 21.4% of controls. The logisticregression demonstrated that NSAID use was significantlyrelated to an increase risk of bleeding both in gastric(odds ratio: 4.98, 95% CI: 1.83-13.6) and duodenal ulcer patients (odds ratio: 10.2, 95% CI: 2.25-46.7) while HP-positivity presented a significantinverse relationship with bleeding only in subjects withgastric lesions (odds ratio: 0.20, 95% CI: 0.07- 0.55). NSAID use and HP infection were alsoshown to be independent, unrelated factors, with theoverall risk of bleeding in HP-positive NSAID usersidentified to be significantly less than in HP-negative NSAID users. In conclusion, in elderlypatients: (1) NSAID use increases the risk of uppergastrointestinal bleeding while HP infection wasassociated with a low risk for gastric bleeding; and (2)the two factors are independent variables, thereforethe HP-positive NSAID user has a lower risk than theHP-negative NSAID user.     

Ranitidine in the treatment of non-steroidal anti-inflammatory drug associated gastric and duodenal ulcers.

In a multicentre study the effect of ranitidine on healing non-steroidal anti-inflammatory drug (NSAID) associated peptic ulcers was compared in a group of patients who had stopped NSAID treatment with another group who continued with NSAID treatment. A total of 190 patients with confirmed ulcers were randomised to continue or stop NSAID treatment. All patients in addition received ranitidine 150 mg twice daily. Patients were endoscopically monitored at four, eight, and 12 weeks. Gastric ulcers at eight weeks had healed in 63% of those taking NSAIDs compared with 95% of those who had stopped NSAID treatment. For duodenal ulcer the healing rates at eight weeks were 84% in the group continuing NSAIDs compared with 100% in those who stopped NSAIDs. The differences in healing rates were statistically significant for both gastric ulcer (p = 0.001) and for duodenal ulcer (p = 0.006). At 12 weeks, 79% of gastric ulcers and 92% of duodenal ulcers were healed in the group continuing with NSAIDs. All patients with gastric and duodenal ulcers who stopped taking NSAIDs were healed at 12 weeks. The study shows that ranitidine 150 mg twice daily effectively heals NSAID associated peptic ulcers. Healing is more successful when NSAID treatment stops but even if these drugs are continued, substantial healing rates are achievable.     

Gastroduodenal Complications of Chronic NSAID Therapy

The fact that nonsteroidal anti-inflammatory drugs (NSAIDs) damage the gastroduodenal mucosa is no longer contested. Endoscopic studies in normal volunteers after NSAID administration have failed to predict which NSAIDs would be safest when administered chronically. NSAID use has been associated with a disproportionately high frequency of upper gastrointestinal bleeding and perforation of ulcers. All of the newer NSAIDs appear to be similar in their propensity to cause mucosal damage, including peptic ulceration. On any given day, more than 10% of patients receiving NSAIDs chronically will have a gastric ulcer, a point prevalence of ulcer disease at least 5 to 10 times higher than in patients who are not taking NSAIDs. The dose-response relationship between anti-inflammatory activity and untoward events, coupled with increased use of newer more potent NSAIDs, explains, in part, the increased incidence of NSAID-associated ulcer complication of bleeding and perforation. The possible association of the increase in prevalence of Campylobacter pylori gastritis with aging and the apparent increase in NSAID-associated complications in the elderly is discussed. The current status of nonsteroidal drug therapy can be summarized as follows: 1) new NSAIDs are not safer than the old NSAIDs, as far as major gastrointestinal side effects are concerned, 2) NSAIDs should be avoided when analgesia is the main goal, 3) if NSAIDs are required, the lowest possible dose that achieves pain relief should be used, 4) newer NSAIDs available only in relatively high anti-inflammatory activity dosages should be restricted to those patients in whom high levels of anti-inflammatory activity are desired.     

Helicobacter pylori and risk of ulcer bleeding among users of nonsteroidal anti-inflammatory drugs: a case-control study.

BACKGROUND & AIMS: Peptic ulcer complications related to use of nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most common serious adverse drug reactions. Whether Helicobacter pylori infection potentiates this gastrointestinal toxicity of NSAIDs is still unresolved. In this study, we investigated the role of H. pylori as a cause of bleeding peptic ulcer among NSAID users. METHODS: A case-control study of current users (n = 132) of NSAIDs (including acetylsalicylic acid), admitted because of bleeding peptic ulcer, was performed. Controls were 136 NSAID users without gastrointestinal complications. H. pylori was diagnosed by either increased levels of serum immunoglobulin G or by 13C-urea breath test. RESULTS: Fifty-eight (44%) case subjects had a bleeding gastric ulcer, 54 (41%) had a bleeding duodenal ulcer, 12 (9%) had both gastric and duodenal ulcers, and 8 (6%) had hemorrhagic gastritis. H. pylori was present in 75 (57%) cases compared with 59 (43%) controls. The adjusted odds ratio of bleeding peptic ulcer among NSAID users associated with H. pylori infection was 1.81 (95% confidence interval, 1.02-3.21). H. pylori accounted for approximately 24% of bleeding peptic ulcers among elderly NSAID users. CONCLUSIONS: NSAID users infected with H. pylori have an almost twofold increased risk of bleeding peptic ulcer compared with NSAID users without H. pylori.     

Gastrointestinal bleeding: dyspeptic symptoms and clinical course in relation to use of non-steroidal antiinflammatory drugs

To study the symptoms of NSAID-associated gastroduodenal bleeding, 94 patients (median age 71 years, range 19-90), were included in a prospective, clinical trial where hematemesis or melena from gastroduodenal ulceration or haemorrhagic/erosive gastritis were the inclusion criteria. NSAID use within one month was studied in relation to subjective symptoms prior to admission and to clinical course of the episode. Significantly fewer of the NSAID users (n = 54) than the non-users (n = 40) had experienced prior peptic ulceration or dyspeptic symptoms. Otherwise, no differences were seen between users and non-users, as regards pre-admission epigastric pain, heartburn or nausea. Also, the clinical course was similar in the two groups. We also found sporadic and regular NSAID use to be similar in this respect. These data do not support the alleged masking of ulcer symptoms by NSAIDs in bleeding ulcers.     

Impact of non-steroidal anti-inflammatory drug and aspirin use on the prevalence of dyspepsia and uncomplicated peptic ulcer disease

BACKGROUND: Non-steroidal anti-inflammatory drug and aspirin (here collectively called NSAIDs) use is the second most common aetiologic factor for peptic ulcer disease and a major factor for peptic ulcer complications. The role of NSAIDs in the pathogenesis of uncomplicated peptic ulcer is less well understood and the interaction between NSAIDs and Helicobacter pylori infection on ulcer development is controversial. The aim of the present study was to examine the role of NSAIDs in the occurrence and clinical features of uncomplicated peptic ulcer disease. METHODS: A total of 1091 consecutive patients referred for open-access upper gastrointestinal endoscopy by general practitioners (GPs) were enrolled. The use of NSAIDs was gathered from a structured questionnaire completed by the patients and from patient files by GPs. The exclusion criteria were previous H. pylori eradication and gastric surgery, as well as symptoms and/or signs suggestive of acute gastrointestinal bleeding. RESULTS: Of the whole study group (n = 1091), 76 (7%) patients had a peptic ulcer. Thirty patients had an NSAID-use-associated peptic ulcer and 46 patients a non-NSAID-use peptic ulcer. Of patients with chronic gastritis (n = 599), 71% were H. pylori-positive and 108 used NSAIDs. Of those with chronic gastritis, 23 had an NSAID-use-associated peptic ulcer and 38 a non-NSAID ulcer. Of patients with normal gastric histology (n = 492), 75 patients used NSAIDs, 7 had an NSAID ulcer and 8 a non-NSAID ulcer. The only independent risk factor for peptic ulcer in patients using NSAIDs was H. pylori infection (odds ratio (OR) 3.1, 95% confidence interval (CI) 1.3-7.3), whereas dyspepsia (OR 1.0, 95% CI 0.4-2.4), male sex (OR 1.4, 95% CI 0.6-3.4), age (OR 1.0 per decade, 95% CI 0.8-1.3) and anaemia (OR 2.9, 95% CI 0.9-8.7) were not risk factors. In patients not using NSAIDs, independent risk factors for peptic ulcer were dyspepsia (OR 4.3, 95% CI 2.1-8.8), male sex (OR 2.0, 95% CI 1.1-2.8), age (OR 1.2 per decade, 95% CI 1.0-1.5), anaemia (OR 6.2, 95% CI 2.6-14.9) and H. pylori infection (OR 7.5, 95% CI 3.4-16.6). When comparing patients using NSAIDs or not, the OR of patients on NSAIDs for peptic ulcer was 2.7 (95% CI 1.5-5.0) among patients with chronic H. pylori gastritis (n = 424) and 5.3 (95% CI 1.8-15.0) among patients with normal gastric mucosa (n = 492). CONCLUSIONS: The use of NSAIDs increases the risk of peptic ulcer 3- and 5-fold in H. pylori-positive and H. pylori-negative patients, respectively. Dyspepsia is a poor predictor of peptic ulcer among patients using NSAIDs, and serologic H. pylori testing and treatment for chronic NSAID users is recommended.     

What consideration should be given to Helicobacter pylori in treating nonsteroidal anti-inflammatory drug ulcers?

Although Helicobacter pylori and nonsteroidal anti-inflammatory drugs (NSAIDs) both cause peptic ulcers, they do so by different mechanisms so any interaction is not necessarily harmful. H. pylori has been shown to enhance gastric mucosal prostaglandin synthesis, while NSAIDs suppress it Pragmatically, there is no compelling evidence in favour of H. pylori eradication in all patients who take NSAIDs. As a broad generalisation, in therapeutic studies of NSAID users, those who have no ulcer at trial entry are more prone to ulcer development if they are H. pylori-positive. By contrast, in those who have ulcers at baseline, H. pylori-positive individuals are less likely to develop ulcers, particularly if taking acid-suppressive therapy. Trials of H. pylori eradication therapy tend to replicate this dichotomy. In one study of patients starting NSAIDs for the first time, with no ulcer history and no baseline ulcer, use of bismuth-based eradication therapy was associated with a lower incidence of gastric ulcer at 2 months. Conversely, in a study of patients with endoscopically proven ulcers and/or troublesome dyspepsia, proton pump inhibitor based eradication treatment had no effect on outcome (of acid suppression) over 6 months. H. pylori eradication has been associated with significantly slower healing of gastric ulcers compared with patients who did not undergo eradication. However, the effect of H. pylori eradication on healing of NSAID-associated duodenal ulcers does not appear to be so dramatic, and limited evidence suggests that it may be possible to prevent H. pylori-associated duodenal ulcer by eradicating the infection. An evidence-based approach to treatment would suggest that NSAID users should undergo H. pylori eradication therapy if they have a duodenal ulcer, whether or not they continue NSAIDs. Because COX-2 inhibitors appear not to be ulcerogenic, management of H. pylori in patients taking these drugs can be based upon the same risk assessment as in patients not taking anti-arthritis drugs. H. pylori eradication should not be used universally or in high-risk gastric ulcer patients who require management with acid suppression.     

Micronutrient antioxidants in gastric mucosa and serum in patients with gastritis and gastric ulcer: does Helicobacter pylori infection affect the mucosal levels?

Free radicals (FRs) play an important role in the pathogenesis of gastroduodenal mucosal inflammation, peptic ulcer disease, and probably even gastric cancer. Various micronutrients protect the gastric mucosa by scavenging FRs. Only limited data is available regarding the concentration of micronutrients in the gastric mucosa in patients with gastritis and peptic ulcer disease. Our aim was to analyze micronutrient antioxidant concentrations in the antral mucosa in patients with gastritis and gastric ulcer and to determine the influence of Helicobacter pylori infection on gastric mucosal antioxidants in patients with gastritis and gastric ulcer. Patients who underwent upper endoscopy for evaluation of dyspepsia were included in the study. Ascorbic acid, alpha-tocopherol, alpha-carotene, beta-carotene, total carotenoids, lutein, cryptoxanthin, and lycopene levels were measured in the sera and antral mucosal biopsies in these patients. The diagnosis of H. pylori was confirmed by histology, urease test (CLO) and serology. Patients with negative endoscopic findings and normal histology and no H. pylori infection served as controls. In patients with gastritis, alpha-tocopherol levels were reduced in serum and mucosa irrespective of H. pylori status, whereas carotenoids and ascorbic acid levels were similar to controls. However, in patients with gastric ulcer, serum and mucosal levels of all micronutrient antioxidants were markedly decreased compared with both controls and patients with gastritis. The degree of depletion of antioxidants was similar in patients with either H. pylori-induced or nonsteroidal antiinflammatory drug (NSAID)-induced ulcers. Patients with gastric ulcer have very low gastric antioxidant concentrations compared to patients with gastritis and normal mucosa. This depletion in antioxidants seems to be a nonspecific response and was not related to H. pylori infection.     

Management of NSAID-associated peptic ulcer disease

Non-steroidal anti-inflammatory drug (NSAID) use increases the risk of gastrointestinal complications such as ulcers or bleeding. The presence of factors like advanced age, history of peptic ulcer, Helicobacter pylori infection and the use of anticoagulants or antiplatelet agents increase this risk further. COX-2 inhibitors and antisecretory drugs, particularly proton pump inhibitors, help to minimize the risk of gastrointestinal complications in high-risk patients. This review presents a practical approach to the prevention and treatment of NSAID-associated peptic ulcer disease and examines the new advances in the rational use of NSAIDs.     

The impact of Helicobacter pylori eradication on peptic ulcer healing

Objective: Current literature was reviewed analyzing the outcome of peptic ulcer healing in relation to the results of the posttherapeutic Helicobacter pylori (HP) status.
Methods: Literature was reviewed along with an analysis of 60 studies, comprising a total of 4329 patients.
Results: Successful Helicobacter pylori eradication was found to induce a better response in peptic ulcer healing, regardless of diagnosis: gastric ulcer 88% vs 73% (odds ratio [OR] 2.7,   p < 0.01  ), duodenal ulcer 95% vs 76% (OR 5.6,   p < 0.0001  ), and peptic ulcer 95% vs 76% (OR 6.6,   p < 0.0001  ), for patients having their HP infection successfully cured versus those remaining HP-positive, respectively (Fisher's exact test). For all evaluated time points (≤ 6, 7–8, and 10–12 wk after beginning treatment), HP-negative patients had higher healing rates than HP-positive patients (95% vs 82%, 94% vs 69%, and 96% vs 78% with corresponding OR of 4.2, 6.5, and 7.4, all   p < 0.0001  , Fisher's exact test). The use of concomitant acid suppression therapy during initial HP eradication provided a benefit on peptic ulcer healing only for patients with persistent HP infection (improved healing rates of 78% vs 67%; otherwise rates were 94–96%). Likewise, prolonged acid inhibition in HP treatment failures after the initial HP treatment phase resulted in 7–20% improved healing rates, whereas patients becoming HP-negative did not profit.
Conclusion: Successful HP eradication therapy accelerates peptic ulcer healing even without concomitant acid suppression.     

Bacterial Mucosal Infiltration in Helicobacter pylori-associated Gastritis: Histological and Clinical Consequences

Objectives: We wished to demonstrate that gastric epithelial cells infiltration by HP is associated with the active inflammatory response and the severity of gastritis in the gastric antrum of patients harboring the bacterium. Methods: We studied 129 patients with HP-associated gastritis and 60 HP-negative controls with gastritis of different origin. Gastric mucosal biopsies were obtained from all subjects at endoscopy and were examined for histological features of active inflammation and type of gastritis, as well as for electronmicroscopical features of invasion and damage, according to a four-degree classification (range 0–3). Results: At entry, the presence of acute inflammatory activity, defined according to the presence of a polymorphonuclear cell infiltrate, was significantly greater in HP-positive patients than in controls ( p < 0.00001) and was well related to the depth of mucosal invasion ( P < 0.001). Accordingly, the prevalence of chronic atrophic gastritis was higher in HP-positive patients ( p < 0.02 vs . controls) and at grade 3 of invasion ( P < 0.04 vs . grade 1 and 2). Peptic ulcers were more frequent in grade 3 patients ( P < 0.04). Conclusion: Gastric epithelial cell infiltration and damage by HP, as assessed by electron microscopy, is an important feature of HP-associated gastritis due to its histological and clinical correlates.     

Risk factors for presentation with bleeding in patients with Helicobacter pylori-related peptic ulcer diseases

At present, there is no study that simultaneously addresses the apparent differences between bacterial and host factors in patients with bleeding and nonbleeding Helicobacter pylori-related ulcer diseases. Therefore, we designed this prospective study to evaluate whether there are identifiable differences between the two groups of patients whose H. pylori-related peptic ulcer diseases present with bleeding or dyspepsia. From July 1996 to November 1996, consecutive patients presenting with upper gastrointestinal bleeding or dyspepsia were enrolled if H. pylori-related ulcer diseases were confirmed. Fifteen clinical, endoscopic, histologic, and serologic factors were tested for association with ulcer bleeding by a logistic regression analysis. In the study period, bleeding occurred in 39 out of 119 patients with H. pylori-related peptic ulcer diseases. Multivariate analysis showed that ingestion of nonsteroidal antiinflammatory drugs (NSAIDs; p = 0.0156; odds ratio = 5:4), ulcer size > or = 1 cm (p = 0.0033; odds ratio = 4:2), and low bacterial density (p = 0.0030; odds ratio = 4:1) were independent factors associated with the risk of bleeding. There were no associations between ulcer bleeding and age, sex, smoking, alcohol consumption, the histologic grade of gastritis, location and number of ulcers, and the cytotoxin-associated gene (CagA) status of H. pylori strain. Therefore, we concluded that H. pylori-related ulcer patients who use NSAIDs or have large ulcers are more likely to present with upper gastrointestinal bleeding; that the CagA-bearing strains are not associated with the development of bleeding complication in patients with peptic ulcer diseases; and that the exact reason concerning the association between low bacterial density and ulcer bleeding merits further investigation.     

Helicobacter pylori infection in elderly dyspeptic patients

The association between Helicobacter pylori (HP) and gastritis is well established. As there is evidence that HP infection increases with age we reviewed the clinicopathological records of 119 consecutive patients aged 65-85 years (mean 71.1 years) on whom gastroscopy had been performed for dyspeptic symptoms. All patients had two antral biopsies--one was assessed for histological evidence of gastritis and the other was independently assessed for evidence of HP infection. Thirty-six patients (30%) had duodenal ulceration, of whom 32 (89%) had an associated HP-positive gastritis. Forty-nine patients (41%) had antral gastritis without ulceration, of whom 38 (78%) were HP positive and 11 (22%) were HP negative. Ninety-one per cent of HP-negative gastritis patients had a history of recent ingestion of non-steroidal anti-inflammatory drugs (NSAID) compared with 29% of HP-positive gastritis patients. Ten patients (8%) had normal antral mucosa but had evidence of reflux oesophagitis (one of these patients was HP-positive). Nineteen patients (16%) had normal antral mucosa and normal endoscopic findings and one of these was HP positive. We conclude that HP infection is associated with the majority of cases of symptomatic gastritis in elderly patients. HP-positive gastritis is associated with the majority of duodenal ulcers. The most important cause of HP-negative gastritis is NSAID ingestion.     

Genotypes of Helicobacter pylori in patients with peptic ulcer bleeding

AIM: Helicobacter pylori causes chronic gastritis, peptic ulcer, gastric cancer and MALT-lymphoma. Different genotypes of Helicobacter pylori are confirmed from diverse geographic areas. Its association with bleeding peptic ulcer remains controversial. The aim of this study was to investigate the Helicobacter pylori vacA alleles, cagA and iceA in patients with bleeding peptic ulcer. METHODS: We enrolled patients with bleeding, non-bleeding peptic ulcers and chronic gastritis. Biopsy specimens were obtained from the antrum of the stomach for rapid urease test, bacterial culture and PCR assay. DNA extraction and polymerase chain reaction were used to detect the presence or absence of cagA and to assess the polymorphism of vacA and iceA. RESULTS: A total of 168 patients (60.4%) (25 patients with chronic gastritis, 26 patients with bleeding gastric ulcer, 51 patients with non-bleeding gastric ulcer, 26 patients with bleeding duodenal ulcer, and 40 patients with non-bleeding duodenal ulcer) were found to have positive PCR results between January 2001 and December 2002. Concerning genotypes, we found cagA (139/278, 50%), vacA s1a (127/278, 45.7%), and ice A1 (125/278, 45%) predominated in all studied patients. In patients with bleeding peptic ulcers, vacA s1a and m1T were fewer than those in patients with non-bleeding peptic ulcers (37/106 vs 69/135, P=0.017, and 4/106 vs 21/135, P =0.002). CONCLUSION: In patients with peptic ulcers, H pylori vacA s1a and m1T prevent bleeding complication.     

Diagnosis and treatment of nonsteroidal anti-inflammatory drug-associated upper gastrointestinal toxicity

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed in the United States to treat pain and reduce inflammation from chronic inflammatory disorders such as rheumatoid arthritis and osteoarthritis. Approximately 40% of older Americans take NSAIDs. Chronic NSAID use carries a risk of peptic ulcer and other gastrointestinal disturbances. This article reviews the diagnosis of medication-induced ulcers based on clinical presentation, laboratory tests, and endoscopic findings to assist the clinician in early diagnosis and appropriate therapy. Risk factors for NSAID-induced ulcers include old age, poor medical status, prior ulcer, alcoholism, smoking, high NSAID dosage, prolonged NSAID use, and concomitant use of other drugs that are gastric irritants, such as alendronate, a bone resorption inhibitor prescribed for osteoporosis. Appropriate treatment options for patients with medication-induced ulcers include dosage reduction, medication substitution, medication withdrawal, antiulcer therapy, and discontinuation of other gastrotoxic drugs.     

Impact of Non-steroidal Anti-inflammatory Drug and Aspirin Use on the Prevalence of Dyspepsia and Uncomplicated Peptic Ulcer Disease

Background: Non-steroidal anti-inflammatory drug and aspirin (here collectively called NSAIDs) use is the second most common aetiologic factor for peptic ulcer disease and a major factor for peptic ulcer complications. The role of NSAIDs in the pathogenesis of uncomplicated peptic ulcer is less well understood and the interaction between NSAIDs and Helicobacter pylori infection on ulcer development is controversial. The aim of the present study was to examine the role of NSAIDs in the occurrence and clinical features of uncomplicated peptic ulcer disease. Methods: A total of 1091 consecutive patients referred for open-access upper gastrointestinal endoscopy by general practitioners (GPs) were enrolled. The use of NSAIDs was gathered from a structured questionnaire completed by the patients and from patient files by GPs. The exclusion criteria were previous H. pylori eradication and gastric surgery, as well as symptoms and/or signs suggestive of acute gastrointestinal bleeding. Results: Of the whole study group (n = 1091), 76 (7%) patients had a peptic ulcer. Thirty patients had an NSAID-use-associated peptic ulcer and 46 patients a non-NSAID-use peptic ulcer. Of patients with chronic gastritis (n = 599), 71% were H. pylori-positive and 108 used NSAIDs. Of those with chronic gastritis, 23 had an NSAID-use-associated peptic ulcer and 38 a non-NSAID ulcer. Of patients with normal gastric histology (n = 492), 75 patients used NSAIDs, 7 had an NSAID ulcer and 8 a non-NSAID ulcer. The only independent risk factor for peptic ulcer in patients using NSAIDs was H. pylori infection (odds ratio (OR) 3.1, 95% confidence interval (CI) 1.3-7.3), whereas dyspepsia (OR 1.0, 95% CI 0.4-2.4), male sex (OR 1.4, 95% CI 0.6-3.4), age (OR 1.0 per decade, 95% CI 0.8-1.3) and anaemia (OR 2.9, 95% CI 0.9-8.7) were not risk factors. In patients not using NSAIDs, independent risk factors for peptic ulcer were dyspepsia (OR 4.3, 95% CI 2.1-8.8), male sex (OR 2.0, 95% CI 1.1-2.8), age (OR 1.2 per decade, 95% CI 1.0-1.5), anaemia (OR 6.2, 95% CI 2.6-14.9) and H. pylori infection (OR 7.5, 95% CI 3.4-16.6). When comparing patients using NSAIDs or not, the OR of patients on NSAIDs for peptic ulcer was 2.7 (95% CI 1.5-5.0) among patients with chronic H. pylori gastritis (n = 424) and 5.3 (95% CI 1.8-15.0) among patients with normal gastric mucosa (n = 492). Conclusions: The use of NSAIDs increases the risk of peptic ulcer 3- and 5-fold in H. pylori-positive and H. pylori-negative patients, respectively. Dyspepsia is a poor predictor of peptic ulcer among patients using NSAIDs, and serologic H. pylori testing and treatment for chronic NSAID users is recommended.     

NSAID-induced ulcers

Opinion statement Nonselective nonsteroidal antiinflammatory drugs (NSAIDs) are used chronically by approximately 13 million to 15 million Americans annually for the treatment of painful and inflammatory conditions. While all these agents are quite effective in reducing inflammation and pain, they are also associated with UGI symptoms and mucosal injury. These include abdominal pain/dyspepsia in the absence of ulcer disease; symptomatic and asymptomatic gastric and duodenal ulcers; and clinically significant upper GI events such as bleeding, gastric outlet obstruction, and perforation. The clinically relevant treatments related to NSAID-associated symptoms and mucosal injury fall into three major categories: symptomatic treatment of dyspepsia while using NSAIDs; treatment of acute endoscopically proven ulcers and ulcer complications in those using these medications; and prevention (prophylaxis) of ulcer and ulcer complications in patients at high risk for ulcer complications. The new COX-2 selective inhibitors are likely to be associated with different short- and long-term safety profiles as compared to traditional NSAIDs; the literature and post-marketing data regarding these agents (celecoxib, rofecoxib) are evolving. As such, this article primarily focuses on the approach to patients using traditional, nonselective, nonsteroidal agents.     

Risk of ulcer bleeding in patients infected with Helicobacter pylori taking non-steroidal anti-inflammatory drugs

OBJECTIVE: To determine whether Helicobacter pylori is an independent risk factor for bleeding peptic ulcer in users of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin. DESIGN: A prospective matched case-control study. SETTING: Odense University Hospital, Denmark. SUBJECTS: 132 patients with a bleeding peptic ulcer (n=124) or haemorrhagic gastritis (n=8) at endoscopy who had taken an NSAID in the previous week and 136 controls who had taken NSAIDs without gastrointestinal complications. The controls were recruited from rheumatology and geriatric outpatient clinics. MEASUREMENTS: H pylori status assessed by serology and 13C-urea breath test and regarded as positive if either test was positive. Data on potential confounding factors including smoking and alcohol were collected by interview. MAIN RESULT: H pylori was present in 57% of cases and 43% of controls. The adjusted odds ratio of bleeding from a peptic ulcer owing to H pylori infection in NSAID users was 1.81 (95% CI 1.02 to 3.21) and was similar in aspirin and non-aspirin NSAID users. Peptic ulcer bleeding was also statistically significantly associated with a history of previous ulcer bleeding, dyspepsia within the previous 3 months, drinking alcohol but not with smoking. About 16% of bleeding peptic ulcers in NSAID users could be attributed to H pylori infection. CONCLUSION: NSAID users infected with H pylori have an almost doubled risk of bleeding peptic ulcer compared with uninfected NSAID users.