Nonsteroidal anti-inflammatory drug use and increased risk for peptic ulcer disease in elderly persons

OBJECTIVE: To evaluate the relative risk for peptic ulcer disease that is associated with the use of nonaspirin nonsteroidal anti-inflammatory drugs. DESIGN: Nested case-control study. SETTING: Tennessee Medicaid program. PARTICIPANTS: Medicaid enrollees 65 years of age or older were included in the study. The 1415 case patients had been hospitalized for confirmed peptic ulcer disease at some point from 1984 through 1986. The 7063 control persons represented a stratified random sample of other Medicaid enrollees. MEASUREMENTS AND MAIN RESULTS: The estimated relative risk for the development of peptic ulcer disease among current users of nonaspirin nonsteroidal anti-inflammatory drugs, compared with that among nonusers, was 4.1 (95% CI, 3.5 to 4.7). For current users, the risk increased with increasing dose, from a relative risk of 2.8 (CI, 1.8 to 4.3) for the lowest to a relative risk of 8.0 (CI, 4.4 to 14.8) for the highest dose category. The risk was greatest in the first month of use (relative risk, 7.2; CI, 4.9 to 10.5). If the association is fully causal, 29% of peptic ulcers in the study sample resulted from the use of these drugs, and the excess risk associated with such use was 17.4 hospitalizations for ulcer disease per 1000 person-years of exposure. CONCLUSIONS: These data support other findings indicating that a clinically significant risk for serious ulcer disease is associated with the use of nonaspirin nonsteroidal anti-inflammatory drugs. The data show that this risk increases with dose and recency of use and that use of these drugs may be responsible for a large proportion of peptic ulcer disease among elderly persons.     

Underutilization of gastroprotective measures in patients receiving nonsteroidal antiinflammatory drugs

OBJECTIVE: To determine the frequency of use of recommended gastroprotective strategies in a cohort of patients receiving recurrent treatment with nonsteroidal antiinflammatory drugs (NSAIDs). METHODS: A cross-sectional study was performed using administrative data from the Tennessee Medicaid (TennCare) program. The study population consisted of 76,765 recurrent recipients of NSAIDs (NSAID users), comprising 24% of the 319,402 persons ages 50 years or older enrolled in the TennCare program from January 1999 through June 2000. Frequency of use of either of 2 recommended gastroprotective strategies, involving either traditional NSAIDs combined with recommended anti-ulcer cotherapy or use of a selective cyclooxygenase 2-inhibiting drug (coxib), was measured and categorized by risk for ulcer complication. RESULTS: Among this cohort of recurrent NSAID users, 16% received 1 of the 2 recommended gastroprotective therapies: 10% received traditional NSAIDs along with antiulcer drugs at the recommended doses and 6% received coxibs. Among those patients with > or=2 risk factors for ulcer complications (age 75 years or older, peptic ulcer or gastrointestinal bleeding in the past year, or concurrent use of oral anticoagulants or corticosteroids), 30% received such gastroprotective therapy. CONCLUSION: Use of recommended strategies to decrease ulcer complications in vulnerable populations is relatively uncommon.     

30-day mortality after peptic ulcer perforation among users of newer selective COX-2 inhibitors and traditional NSAIDs: a population-based study

OBJECTIVES: Nonsteroidal anti-inflammatory drug (NSAID) use is a strong risk factor for peptic ulcer perforation, yet little is known about the outcome of this condition among NSAID users. We examined 30-day mortality after peptic ulcer perforation associated with the use of traditional NSAIDs and newer selective cyclo-oxygenase-2 (COX-2) inhibitors. METHODS: We conducted a cohort study of patients with the first hospitalization for peptic ulcer perforation, identified in discharge registries of three Danish counties between 1991 and 2003. Data on preadmission NSAID use, other ulcer-related drugs, and comorbidity were likewise from population-based registries. Mortality was ascertained from the Civil Registration System. We compared 30-day mortality in NSAID users and nonusers while adjusting for age, gender, comorbidity, previous uncomplicated peptic ulcer, and ulcer medication use. RESULTS: Of the 2,061 patients hospitalized with peptic ulcer perforation, 38% were current NSAID users. The 30-day mortality was 25% overall, and 35% among current NSAID users. Compared with never-use, the adjusted 30-day mortality rate ratios (MRRs) were 1.8 (95% CI 1.4-2.3) for current use of NSAIDs alone and 1.6 (95% CI 1.2-2.2) for current use combined with other ulcer-associated drugs. The mortality increase associated with the use of COX-2 inhibitors was similar to that of traditional NSAIDs: adjusted MRR for users of COX-2 inhibitors alone and in combination, 2.0 (1.3-3.1) and 1.4 (0.8-2.5), and for users of traditional NSAIDs alone or in combination, 1.7 (1.3-2.3) and 1.6 (1.2-2.3). CONCLUSION: Current use of NSAIDs, including COX-2 inhibitors, is associated with a poor prognosis for patients hospitalized with peptic ulcer perforation.     

Risk of peptic ulcer hospitalizations in users of NSAIDs with gastroprotective cotherapy versus coxibs

BACKGROUND & AIMS: The primary strategies to reduce the risk of serious gastropathy caused by traditional nonsteroidal anti-inflammatory drugs (NSAIDs) are use of a coxib or concurrent use of a proton pump inhibitor or double-dose histamine-2 receptor antagonist. However, the relative clinical effectiveness of these therapeutic alternatives is understudied. METHODS: We studied peptic ulcer hospitalizations in a cohort of Tennessee Medicaid enrollees between 1996 and 2004. To decrease potential "channeling" bias, the study included only new episodes of prescribed NSAID or coxib use and controlled for multiple baseline risk factors for upper gastrointestinal disease. There were 234,010 and 48,710 new episodes of NSAID and coxib use, respectively, with 363,037 person-years of follow-up and 1223 peptic ulcer hospitalizations. RESULTS: Current users of NSAIDs with no gastroprotective cotherapy had an adjusted incidence of peptic ulcer hospitalizations of 5.65 per 1000 person-years, 2.76 (95% confidence interval, 2.35-3.23) times greater than that for persons not currently using either NSAIDs or coxibs. This risk was reduced by 39% (16%-56%, 95% CI) for current users of NSAIDs with gastroprotective cotherapy and 40% (23%-54%) for current users of coxibs without such cotherapy. Concurrent users of NSAIDs and proton pump inhibitors had a 54% (27%-72%) risk reduction, very similar to the 50% (27%-66%) reduction for concurrent users of proton pump inhibitors and coxibs. CONCLUSIONS: These findings suggest that coprescribing a proton pump inhibitor with an NSAID is as effective as use of a coxib for reducing the risk of NSAID-induced gastropathy.     

Gastrointestinal toxicity associated with nonsteroidal anti-inflammatory drugs. Epidemiologic and economic issues.

The large body of literature on the gastrointestinal side effects of NSAIDs has shown consistently that populations can be identified that have a markedly elevated risk for these iatrogenic conditions. These groups include the elderly, persons with prior history of peptic ulcer disease and its complications, persons receiving anticoagulant and corticosteroid therapy, and persons who require long-term NSAID therapy, especially at high dose. It is possible that several comorbidities (e.g., rheumatoid arthritis) predispose patients to gastrointestinal complications caused by NSAIDs, but few studies have adjusted carefully for the possibility that concomitant medication use (e.g., oral anticoagulants, corticosteroids) or increased NSAID dose may account best for apparent association of comorbidities as a risk factor for serious gastrointestinal events. The role of H. pylori infection in affecting the risk of complicated ulcer disease among NSAID users remains to be fully elucidated. Low-dose aspirin for cardioprotective use is associated with an increased risk for PUBs; when used concomitantly with NSAIDs, this increases the risk of PUBs above that of the NSAID itself. Apart from the physical toll NSAID-related gastrotoxicity places on the patient, there are considerable economic consequences to patients, providers, and society. This cost presents a subject for research for those interested not only in improving the quality of patient care, but also in the prudent use of health care resources.     

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.     

Clinical significance of cytotoxin-associated gene A status of Helicobacter pylori among non-steroidal anti-inflammatory drug users with peptic ulcer bleeding: a multicenter case-control study

BACKGROUND: The role of Helicobacter pylori infection and especially of the cytotoxin-associated gene A (CagA) product strain in peptic ulcer bleeding among non-steroidal anti-inflammatory drugs (NSAIDs) users remains controversial. METHODS: A case-control study was carried out including 191 consecutive chronic NSAIDs users admitted to hospital because of peptic ulcer bleeding. Peptic ulcer was verified by endoscopy. Controls comprised 196 chronic NSAIDs users without signs of bleeding of similar age and gender to cases. Multivariate regression analysis was performed for further evaluation of the relationship between H. pylori, CagA status and other risk factors. RESULTS: H. pylori infection was present in 121 (63.4%) cases compared with 119 (60.7%) controls (odds ratio (OR) = 1.14, 95% CI, 0.76-1.72). CagA-positive strains were found to be significantly more frequent in cases than in controls (65/106 versus 41/99 P = 0.008). Current smoking (OR = 2.65; 95% CI, 1.14-6.15; P= 0.02), CagA status (OR = 2.28; 95% CI, 1.24-4.19; P = 0.008), dyspepsia (OR = 6.89; 95% CI, 1.84-25.76; P = 0.004) and past history of peptic ulcer disease (OR=3.15; 95% CI, 1.43-6.92; P=0.004) were associated significantly with increased risk of bleeding peptic ulcer. CONCLUSIONS: The results suggest that CagA-positive H. pylori infection is associated with a more than 2-fold increased risk of bleeding peptic ulcer among chronic NSAIDs users.     

Reserpine reconsidered

A history of peptic ulcer disease is frequently cited as a contraindication to the use of reserpine. However, the risk of ulcer disease associated with the use of reserpine at current therapeutic doses is unknown. To address this question, the authors conducted a nested case-control study of the association between reserpine use and hospitalizations for peptic ulcer disease in elderly Tennessee Medicaid enrollees. When compared with that of nonusers of reserpine, the relative risk of hospitalization for peptic ulcer disease was 0.8 (95% CI, 0.6–1.0) among current users and 0.8 (95% CI, 0.5 –1.3) among former users. The authors’ data provide evidence that reserpine is not associated with ulcer disease in elderly persons and suggest that a history of ulcer disease need not be a contraindication to the use of this drug. Received from the Division of Pharmacoepidemiology, Department of Preventive Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2637. Supported in part by FDA Cooperative Agreement^#FD-U-000073. Dr. Shorr is the recipient of an NIA Clinical Investigator Award (K08-00559).     

Peptic ulcer bleeding: accessory risk factors and interactions with non-steroidal anti-inflammatory drugs

AIMS: To determine risk factors for peptic ulcer bleeding other than non-steroidal anti-inflammatory drugs (NSAIDs). Methods-Data on possible antecedent risk factors obtained in a large case control study of 1121 patients admitted to hospitals in Glasgow, Newcastle, Nottingham, Oxford, and Portsmouth with bleeding peptic ulcers were compared with the same information obtained in 989 population controls. Data were analysed by logistic regression with the calculation of odds ratios (OR) and 95% confidence intervals (CI). RESULTS: From a logistic regression model, oral anticoagulants (OR 7. 8; 95% CI 2.8-21.5), previous peptic ulcer (3.8; 2.6-4.9), treatment for heart failure (5.9; 2.3-13.1), oral corticosteroid use (2.7; 1. 3-4.5), treatment for diabetes (3.1; 1.2-4.3), and current smoking (1.6; 1.2-2.0) were all independent risk factors. No association was found with use of calcium channel antagonists. Odds ratios for concomitant NSAID usage were multiplicative with the exception of current smoking. CONCLUSIONS: Some 45% of admissions for peptic ulcer bleeding in England and Wales in those aged 60 or more are calculated to be attributable to, or associated with, these accessory risk factors, which, together with those associated with aspirin or other NSAID use will account for over 80% of predisposing factors to ulcer bleeding.     

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.     

Use of oral corticosteroids and the risk of acute myocardial infarction

INTRODUCTION: A few epidemiological studies suggested an increased coronary heart disease (CHD) risk with high doses of oral corticosteroids. METHODS: We performed a cohort study with nested case-control analysis to estimate the risk of acute myocardial infarction (AMI) associated with the use of oral corticosteroids by dose and duration. We followed-up 404,183 persons, 50-84 years old, without cancer from the general UK population. After validation of a random sample (confirmation rate of 96%), we included 4795 hospitalised cases of AMI or CHD deaths. We randomly sampled 20,000 controls, frequency matched by sex, age and calendar year. Relative risks were estimated using unconditional logistic regression. RESULTS: The adjusted OR for AMI in current users of oral corticosteroids compared to non-users was 1.42 (95% CI: 1.17-1.72). The risk during the first 30 days of use (OR=2.24; 95% CI: 1.56-3.20) was greater than with longer duration (OR=1.22; 95% CI 0.98-1.52). The risk was more pronounced (OR=2.15; 95% CI 1.45-3.14) among users of prednisolone equivalent doses >10mg/day. The dose effect was observed both among patients with and without CHD or COPD/asthma. CONCLUSION: These results suggest a small increased risk of AMI with oral corticosteroid use with a greater risk observed among users of high corticosteroid dose.     

Clinical significance of cytotoxin-associated gene A status of Helicobacter pylori among non-steroidal anti-inflammatory drug users with peptic ulcer bleeding: a multicenter case-control study

Background: The role of Helicobacter pylori infection and especially of the cytotoxin-associated gene A (CagA) product strain in peptic ulcer bleeding among non-steroidal anti-inflammatory drugs (NSAIDs) users remains controversial. Methods: A case-control study was carried out including 191 consecutive chronic NSAIDs users admitted to hospital because of peptic ulcer bleeding. Peptic ulcer was verified by endoscopy. Controls comprised 196 chronic NSAIDs users without signs of bleeding of similar age and gender to cases. Multivariate regression analysis was performed for further evaluation of the relationship between H. pylori, CagA status and other risk factors. Results:H. pylori infection was present in 121 (63.4%) cases compared with 119 (60.7%) controls (odds ratio (OR)?=?1.14, 95% CI, 0.76-1.72). CagA-positive strains were found to be significantly more frequent in cases than in controls (65/106 versus 41/99 P?=?0.008). Current smoking (OR?=?2.65; 95% CI, 1.14-6.15; P?=?0.02), CagA status (OR?=?2.28; 95% CI, 1.24-4.19; P?=?0.008), dyspepsia (OR?=?6.89; 95% CI, 1.84-25.76; P?=?0.004) and past history of peptic ulcer disease (OR?=?3.15; 95% CI, 1.43-6.92; P?=?0.004) were associated significantly with increased risk of bleeding peptic ulcer. Conclusions: The results suggest that CagA-positive H. pylori infection is associated with a more than 2-fold increased risk of bleeding peptic ulcer among chronic NSAIDs users.     

Should we eradicate Helicobacter pylori infection in patients receiving nonsteroidal anti-inflammatory drugs or low-dose aspirin?

Whether Helicobacter pylori infection alters the risk of ulcer disease in patients receiving nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin is one of the most controversial topics in peptic ulcer research. This is an important management issue, particularly in countries where peptic ulcer disease is common and the prevalence of H. pylori infection is high. Current evidence shows that H. pylori infection increases the ulcer risk associated with NSAIDs or low-dose aspirin. Eradication of H. pylori reduces the subsequent risk of endoscopic and complicated ulcers in patients who are about to start long-term NSAIDs. Among patients with H. pylori infection and a history of ulcer bleeding who continue to use low-dose aspirin, 1 week of eradication therapy prevents recurrent ulcer bleeding. Failure of eradication and concomitant use of NSAIDs, however, account for most cases of recurrent bleeding with low-dose aspirin. The apparent protective effect of H. pylori in long-term NSAIDs users reported in some studies was actually the weeding out of susceptible patients who were intolerant to NSAIDs. There is no convincing evidence that eradication of H. pylori has any clinically important adverse effect on the healing and prevention of ulcers in NSAIDs users.     

Association between nonsteroidal anti-inflammatory drugs and upper gastrointestinal tract bleeding/perforation: an overview of epidemiologic studies published in the 1990s

BACKGROUND: In the last decades, studies have estimated the upper gastrointestinal tract bleeding/perforation (UGIB) risk associated with individual nonsteroidal anti-inflammatory drugs (NSAIDs). Later analyses have also included the effect of patterns of NSAID use, risk factors for UGIB, and modifiers of NSAID effect. METHODS: Systematic review of case-control and cohort studies on serious gastrointestinal tract complications and nonaspirin NSAIDs published between 1990 and 1999 using MEDLINE. Eighteen original studies were selected according to predefined criteria. Two researchers extracted the data independently. Pooled relative risk estimates were calculated according to subject and exposure characteristics. Heterogeneity of effects was tested and reasons for heterogeneity were considered. RESULTS: Advanced age, history of peptic ulcer disease, and being male were risk factors for UGIB. Nonsteroidal anti-inflammatory drug users with advanced age or a history of peptic ulcer had the highest absolute risks. The pooled relative risk of UGIB after exposure to NSAIDs was 3.8 (95% confidence interval, 3.6-4.1). The increased risk was maintained during treatment and returned to baseline once treatment was stopped. A clear dose response was observed. There was some variation in risk between individual NSAIDs, though these differences were markedly attenuated when comparable daily doses were considered. CONCLUSIONS: The elderly and patients with a history of peptic ulcer could benefit the most from a reduction in NSAID gastrotoxicity. Whenever possible, physicians may wish to recommend lower doses to reduce the UGIB risk associated with all individual NSAIDs, especially in the subgroup of patients with the greatest background risk.     

Relation of upper gastrointestinal bleeding to non-steroidal anti-inflammatory drugs and aspirin: a case-control study.

We conducted a case-control study in five general hospitals in the region of Antwerp, studying 161 patients (102 men, 59 women) and hospital control subjects matched for age and sex to explore the relation between drug use and upper gastrointestinal bleeding from 'erosive lesions' (peptic oesophagitis, gastric erosions, gastric ulcer(s), or duodenal ulcer(s]. There was a highly significant difference between cases and control subjects in the use of non-steroidal anti-inflammatory drugs (NSAIDs, excluding aspirin) (odds ratio 7.4, p less than 0.001; 95% confidence interval odds ratio 3.7 to 14.7). There also was a significant difference in the use of aspirin (odds ratio 2.2, p = 0.025; 95% CI odds ratio 1.3 to 4.0) and a highly significant difference regarding the presence of antecedents of peptic ulcer disease (odds ratio 5.5, p less than 0.001; 95% CI odds ratio 3.2 to 9.6). There was no significant difference in the use of other drugs, paracetamol and corticosteroids in particular, nor in the use of alcohol or tobacco. The patient group using NSAIDs was older, had more women, and had a higher mortality than the group not using NSAIDs. Among patients with bleeding gastric or duodenal ulcer(s), NSAID users were not more or less likely to have had symptoms of peptic ulcer disease, and had no higher frequency of multiple gastric or duodenal ulcers. The attributable risk for NSAID use was 0.30 (95% CI 0.23 to 0.37) and for aspirin use 0.14 (95% CI 0.08 to 0.20).     

Diagnosis and Treatment of Peptic Ulcer Disease

Peptic ulcer disease continues to be a source of significant morbidity and mortality worldwide. Approximately two-thirds of patients found to have peptic ulcer disease are asymptomatic. In symptomatic patients, the most common presenting symptom of peptic ulcer disease is epigastric pain, which may be associated with dyspepsia, bloating, abdominal fullness, nausea, or early satiety. Most cases of peptic ulcer disease are associated with Helicobacter pylori infection or the use of nonsteroidal anti-inflammatory drugs (NSAIDs), or both. In this review, we discuss the role of proton pump inhibitors in the management of peptic ulcer disease, highlight the latest guidelines about the diagnosis and management of H. pylori, and discuss the latest evidence in the management of complications related to peptic ulcer disease, including endoscopic intervention for peptic ulcer-related bleeding. Timely diagnosis and treatment of peptic ulcer disease and its sequelae are crucial in order to minimize associated morbidity and mortality, as is prevention of peptic ulcer disease among patients at high risk, including those infected with H. pylori and users of NSAIDs.     

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.     

The Risk of Sepsis with Inhaled and Oral Corticosteroids in Patients with COPD

The use of oral and inhaled corticosteroids is associated with increases in the risk of infection, especially pneumonia. The risk of sepsis with corticosteroid treatment in patients with chronic obstructive pulmonary disease (COPD) has been little studied, however. We assessed whether the use of inhaled and oral corticosteroids in COPD is associated with an increase in the risk of sepsis. We carried out a retrospective cohort study using the administrative health databases of the province of Quebec, Canada, over the period 1990–2007. The cohort of patients with COPD included patients aged 55 years or older who used respiratory medications. A quasi-cohort analysis was used to estimate the rate ratio (RR) of sepsis in current users of inhaled corticosteroids and oral corticosteroids separately, after adjusting for differences in COPD disease severity and co-morbid conditions. The cohort included 163,514 patients treated for COPD, including 1,704 who were hospitalized for or died with sepsis during follow-up (incidence rate 1.94 per 1000 per year). The RR of sepsis associated with current use of inhaled corticosteroids was 0.98 (95%confidence interval [CI] 0.84–1.14). Current oral corticosteroid use was associated with a 66% increase in the risk of sepsis (RR 1.66; 95% CI: 1.35–2.05). The increase in risk remains for around 5 months after the oral corticosteroid exposure. Among patients treated for COPD, the risk of sepsis is not increased with inhaled corticosteroids, even at high doses, while the risk is increased with oral corticosteroids. This risk should be considered when treating exacerbations of COPD.     

Should we eradicate Helicobacter pylori infection in patients receiving nonsteroidal anti‐inflammatory drugs or low‐dose aspirin?

Whether Helicobacter pylori infection alters the risk of ulcer disease in patients receiving nonsteroidal anti‐inflammatory drugs (NSAIDs) or low‐dose aspirin is one of the most controversial topics in peptic ulcer research. This is an important management issue, particularly in countries where peptic ulcer disease is common and the prevalence of H. pylori infection is high. Current evidence shows that H. pylori infection increases the ulcer risk associated with NSAIDs or low‐dose aspirin. Eradication of H. pylori reduces the subsequent risk of endoscopic and complicated ulcers in patients who are about to start long‐term NSAIDs. Among patients with H. pylori infection and a history of ulcer bleeding who continue to use low‐dose aspirin, 1 week of eradication therapy prevents recurrent ulcer bleeding. Failure of eradication and concomitant use of NSAIDs, however, account for most cases of recurrent bleeding with low‐dose aspirin. The apparent protective effect of H. pylori in long‐term NSAIDs users reported in some studies was actually the weeding out of susceptible patients who were intolerant to NSAIDs. There is no convincing evidence that eradication of H. pylori has any clinically important adverse effect on the healing and prevention of ulcers in NSAIDs users.