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Background and aims: Factors predisposing to endoscopic ulcer formation or healing with non-steroidal anti-inflammatory drugs (NSAIDs) have not been well defined. Methods: We used multivariate analysis of data from three [...]

Background and aims: 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 [...]

Long-term therapy with low-dose aspirin (acetylsalicylic acid; ASA), 75-325 mg, is highly effective for the secondary prevention of cardiovascular (CV) events. For high-CV-risk patients to attain the full benefits of this therapy, it is important that treatment is continuous and that good compliance is maintained over the long term. We aimed to quantify the level of, and investigate the reasons for, patient-driven non-compliance and treatment discontinuation among patients taking low-dose ASA for the prevention of CV events. We therefore performed a systematic search of the PubMed, Embase, and Cochrane databases using the terms 'aspirin' AND 'patient compliance' OR 'withdrawal', with no restrictions on the start date and up to July 2008. A total of 32 studies, summarizing >144 800 patients, were selected from over 400 results for inclusion. Poor compliance (defined differently among the studies included) with low-dose ASA therapy ranged from approximately 10% to over 50%, and patient-initiated discontinuation of therapy occurred in up to 30% of patients. Common predictors of both non-compliance and treatment discontinuation were lower education level, female sex, or a history of depression, diabetes mellitus, or cigarette smoking. Adverse events were cited as the reason for low-dose ASA discontinuation in almost 50% of patients. The findings of this review suggest that poor compliance is common among patients receiving low-dose ASA therapy, placing them at substantial risk of CV events. By addressing barriers to compliance with low-dose ASA therapy, healthcare professionals can improve CV risk management for such patients. [ABSTRACT FROM AUTHOR]

Objective: To compare the impact on quality of life (QoL) of omeprazole and misoprostol during healing, and omeprazole, misoprostol, and placebo during maintenance treatment in chronic NSAID users with NSAID-associated gastroduodenal lesions.Methods: Validated baseline and follow-up QoL questionnaires were completed by 610 patients (healing: after 4/8 weeks; maintenance: after 6 months).Results: Patients with arthritis being treated with NSAIDs have a poor QoL. Rheumatoid arthritis causes more joint problems and physical mobility limitations than osteoarthritis. Chronic NSAID use causes heartburn and dyspepsia. QoL improved on both treatments (about equally on two general QOL scales), but omeprazole relieved gastrointestinal symptoms more than misoprostol, particularly reflux, abdominal pain and indigestion symptoms. During maintenance, both treatments maintained QoL, but misoprostol induced diarrhoea.Conclusion: QoL in arthritis patients on chronic NSAID treatment is destroyed. Omeprazole is superior to misoprostol for relief and prevention of NSAID-associated gastrointestinal symptoms allowing continued NSAID treatment without compromising the patients' QoL. [ABSTRACT FROM AUTHOR]

The possible presence of parietal cell stimulating antibodies was examined in sera from 57 patients with relapsing ulcer disease. The sera were obtained at the time of symptomatic relapse and all patients had ulcers confirmed by endoscopy. A sensitive assay based on adenosine 3':5' cyclic monophosphate (cAMP) production in isolated porcine gastric mucosal cells was used as a measure. cAMP production increased up to four hours of incubation and was histamine responsive; an approximately 20-fold increase was found with histamine 10(-4) mol/l. Sera from both patients and healthy control subjects showed some inhibitory effect on basal cAMP production compared with incubation in medium only, whereas immunoglobulin preparations had a weaker non-specific effect. No stimulation was found when the patients' sera and immunoglobulins (up to a concentration of 6 mg/ml) were examined. These results suggest that gastric acid hypersecretion in duodenal ulcer disease is not an effect of histamine receptor stimulating antibodies. The data thus argue against a recent hypothesis that severe chronic ulcer disease in some patients has an autoimmune origin. [ABSTRACT FROM PUBLISHER]

We tested the hypothesis that the gastric H+/K+ adenosine triphosphatase inhibitor, omeprazole, because of its different mode of action and pronounced inhibitory effect on gastric acid secretion, may be more effective in peptic ulcer that is refractory to histamine H2 receptor antagonist treatment than continuing the same therapy. Altogether 107 patients (duodenal ulcer, n = 88; prepyloric ulcer, n = 14; gastric ulcer, n = 3; mixed sites, n = 2) with refractory peptic ulcer - that is ulcer unhealed after at least two months' treatment with cimetidine 0.8 g or 1 g daily or with ranitidine 0.3 g daily - were randomly allocated to receive either omeprazole 40 mg daily (n = 54) or to continue treatment with the same H2 receptor antagonist and at the same dose (n = 53) for up to eight weeks. The patients in the two treatment groups were well matched demographically. Healing by 'intent to treat' analysis was as follows: at four weeks, omeprazole 46 of 54 (85%), H2 receptor antagonist 18 of 53 (34%) (p less than 0.0001); and at eight weeks, 52 of 54 (96%) and 30 of 53 (57%) respectively (p less than 0.0001). One patient was lost to follow up but of the 22 patients whose ulcers were shown to be unhealed at endoscopy after receiving continued H2 receptor antagonist treatment, 21 healed in four to eight weeks when changed to omeprazole. Daytime epigastric pain cleared at four weeks in 43 of 47 (91%) patients on omeprazole and in 32 of 46 (70%) on H2 receptor antagonists (p=0.01) and relief of all dyspeptic symptoms occurred in 39 of 47 (83%) and 23 of 45 (51%) (p=0.0009) patients respectively. Adverse events occurred in 11 of 54 (20%) patients on omeprazole and in 12 of 35 (34%) on cimetidine but in none on ranitidine. The events were mild and none required treatment withdrawal. The commonest event in patients on omeprazole was loose stools or diarrhoea (n=5). Omeprazole was significantly better than continued H2 receptor antagonist treatment for the short term management of refractory peptic ulcer as judged by healing rate and pain relief, and it was safe. [ABSTRACT FROM PUBLISHER]

Tests the effects of a single dose of A-64077 (5-lipoxygenase inhibitor) on concentrations of leukotriene B4 and prostaglandin E2 in rectal dialysis fluid from patients with relapsing ulcerative colitis. Patients and methods; Results; Discussion.

Background: Continuous low-dose acetylsalicylic acid (aspirin; ASA) is a mainstay of cardiovascular (CV) risk management. It is well established, however, that troublesome upper gastrointestinal (GI) symptoms are commonly experienced among low-dose ASA users., Objective: The objective of this study was to investigate the occurrence of upper GI symptoms, and their impact on well-being, among patients taking low-dose ASA for CV risk management., Study Design: This was a multicenter, non-interventional, 12-week study carried out in primary-care, cardiology, and practice group centers in the USA, Canada, and France., Patients: Eligible patients were adults (age ≥18 years) at risk of or with confirmed CV disease, with physician-prescribed/-recommended low-dose ASA (75-325 mg) use., Main Outcome Measures: An electronic device (eDiary) was used to collect patient-reported outcome data three times per day (morning, afternoon, and evening; regular reports), including upper GI (gastroesophageal disease [GERD]-like or dyspepsia-like) symptoms and the impact of such symptoms on sleep quality, perceived stress, and emotions. In addition to regular reports, patients were able to self-initiate a report of upper GI symptoms (spontaneous reports)., Results: Overall, 81,282 eDiary reports (including 4,407 spontaneous reports of upper GI symptoms) were collected from 340 patients. Upper GI symptoms (most commonly GERD-like) were commonly blamed on food/drink (39 %), and around one-third of patients (37 %) used medication to relieve their symptoms. Analysis showed that upper GI symptoms had a negative impact on sleep quality, perceived stress, and emotions (all p < 0.01). Overall, GI medication use was infrequent, but was more common among low-dose ASA-experienced patients (41 % vs. 12 % of evening reports in patients naïve to low-dose ASA at baseline; p < 0.01); adherence to prescribed daily proton pump inhibitors (PPIs) was poor (47 %)., Conclusion: Upper GI symptoms impact negatively on well-being among low-dose ASA users, in terms of decreased quality of sleep, increases in perceived stress, and negative impact on emotions. Despite this, patients may not necessarily associate these symptoms with their low-dose ASA therapy and do not readily take steps to manage such symptoms, which extends to poor adherence to prescribed daily PPIs.

Background: Disease burden and associated costs are not well understood among patients with gastroesophageal reflux disease (GERD) who have persistent symptoms despite optimized proton pump inhibitor (PPI) therapy. The aim of this study was to investigate disease burden and costs of GERD in partial responders to PPI therapy., Methods: The Partial Response to PPI treatment: the Cost to Society and the Burden to the Patient in the US (REMAIN US) study was a 12-month, multicenter, noninterventional, observational study of 552 partial PPI responders in the USA. Participating sites were comprised of family practice (n = 30), internal medicine (n = 8), and specialist (gastroenterologist) centers (n = 15). GERD symptoms, health-related quality of life (HRQL), and impact on productivity were evaluated from patient-reported outcome instruments. Resource utilization data were also collected., Results: Patients had a high symptom burden, impaired HRQL, and reduced productivity while at work and in daily activities, despite optimized PPI therapy. Mean annual GERD-related costs were US$9944 per patient, comprising total direct costs and mean productivity loss costs of US$4068 and US$5876 per patient, respectively., Conclusion: Patients with GERD and a partial response to PPI therapy have considerable direct and indirect costs, along with substantial impairments in HRQL and productivity.

Objective: The aim of this study was to investigate the bioequivalence of a single oral dose of esomeprazole 40 mg and acetylsalicylic acid 325 mg when formulated as a single capsule, relative to the components given as separate monotherapies., Methods: This was an open, randomized, single-center, single-dose, 2-stage group sequential design, 2-way crossover study (NCT00688428) in 49 healthy adult volunteers (29 women). In each treatment period, subjects received a single dose of esomeprazole 40 mg and ASA 325 mg formulated as a single capsule or as separate monotherapies given in combination. Treatment periods were separated by a washout period of at least 6 days. The bioequivalence of a single-capsule formulation of esomeprazole 40 mg and ASA 325 mg relative to the monotherapies given individually was assessed by the geometric mean ratios of the area under the plasma concentration-time curve (AUC) and observed maximum plasma concentration (Cmax). If the 94% confidence interval (CI) of the geometric mean ratios of AUC and Cmax were within 0.80 - 1.25, bioequivalence would be established. A 94% CI was used to compensate for the multiple analyses of the study design, and to assure that the actual overall confidence level was 90%., Results: The geometric mean ratios of the AUC for esomeprazole 40 mg and ASA 325 mg when administered in the single capsule formulation, relative to the monotherapies were 0.97 (94% CI, 0.90 - 1.04) and 1.04 (94% CI, 1.00 - 1.08). The corresponding mean geometric ratios for Cmax were 0.99 (94% CI, 0.90 - 1.09) and 1.02 (94% CI, 0.92 - 1.13)., Conclusions: Treatment with esomeprazole 40 mg and ASA 325 mg formulated as a single capsule is bioequivalent to the separate monotherapies of esomeprazole 40 mg and ASA 325 mg when given in combination as separately-administered drugs in healthy adult subjects.

Background: Low-dose acetylsalicylic acid (ASA; 75-325 mg) is a mainstay of therapy for patients at high risk of cardiovascular (CV) events. However, in some patients, such treatment is associated with upper gastrointestinal (GI) adverse effects, e.g. dyspeptic symptoms, peptic ulceration, and GI bleeding, that may interfere with adequate adherence to, and continuation of, low-dose ASA for CV protection., Objective: The objective of this study was to explore the extent of, and drivers for, poor adherence to, and discontinuation of, low-dose ASA treatment for CV protection among a representative sample of patients in the US with GI problems., Methods: An online questionnaire was completed by eligible US adult patients (aged ≥20 years) who had been recommended low-dose ASA by a healthcare professional for secondary CV prevention or high-risk primary CV prevention (defined as diabetes mellitus or three or more risk factors for CV disease) and had experience of upper GI problems. Participants were asked questions about their demographic profile, general health, and attitudes towards low-dose ASA use. Patients were classified as 'lapsers' if they reported no longer regularly taking low-dose ASA; patients were also asked if they ever took deliberate, short-term breaks from their low-dose ASA regimen ('breakers'). Statistical analysis was descriptive., Results: From 56 296 invitation emails that were sent out, 1007 questionnaires were completed in full and were eligible for the analysis. The main reason for ineligible responses was unread emails. Respondents had a mean age of 52 years and 59% were women. Some 57% of patients were categorized as being at high primary CV risk and 43% were categorized as secondary CV prevention patients. A total of 67% of all patients used ASA at a daily dose of 81 mg. Overall, 28% of patients were considered to be poorly adherent through lapsing and/or taking deliberate, short-term breaks, and those receiving low-dose ASA for secondary CV prevention were more likely to be poorly adherent than were high-risk primary CV prevention patients (32% vs 25%). Of the overall population, 15% were lapsers (12% of secondary and 18% of high-risk primary CV prevention patients). The most common spontaneously reported reasons for lapse of low-dose ASA therapy were contraindicated combinations of medications and 'stomach problems'. Deliberate, short-term breaks from treatment were reported by 19% of all patients (24% of secondary and 15% of high-risk primary CV prevention). The most common spontaneously reported reasons for breaks were 'stomach problems' and preparation for surgery. Overall, 88% of patients reported experiencing heartburn or acid reflux symptoms. Self-reported rates of GI problems were greater in secondary than in high-risk primary CV prevention patients., Conclusion: Among the US cohort studied (i.e. low-dose ASA users with experience of upper GI problems), poor adherence to low-dose ASA treatment for both secondary and high-risk primary CV prevention was common.

Background: While low-dose acetylsalicylic acid (ASA [aspirin]; 75-325 mg) is a mainstay of cardiovascular (CV) protection in patients at high risk of CV events, such protection may be compromised due to poor adherence (or discontinuation) resulting from gastrointestinal (GI) adverse events. To date, however, the link between GI adverse events and nonadherence to, and discontinuation of, low-dose ASA is not well established in the literature., Objective: The aim of this study was to characterize the real-world impact of upper GI symptoms on low-dose ASA nonadherence and discontinuation in patients with CV risk taking low-dose ASA for CV protection., Study Design: Multicenter, observational, noninterventional study., Setting: Primary-care, cardiology, and practice group centers in the US, Canada, and France., Patients: Subjects aged ≥18 years at risk of, or with confirmed, CV disease, and who had been prescribed or recommended low-dose ASA (75-325 mg daily) by a physician., Main Outcome Measure: Adherence to low-dose ASA was assessed using 3 months of data prospectively collected using an electronic diary (completed at least three times/day). Adherence was defined as low-dose ASA intake of ≥75% over the 3-month eDiary phase. Discontinuation was defined as no reported low-dose ASA intake for ≥7 continuous days. The odds of daily adherence were calculated using a mixed-model analysis for repeated measures, and a Cox-proportional hazard model was used to assess the association between upper GI symptoms and time to discontinuation of low-dose ASA., Results: Overall, 340 patients (mean age 50 years; 59% women) participated in the analysis. Most patients (75%) were low-dose ASA naïve at inclusion, and had not experienced upper GI symptoms within the previous 14 days. Among these patients, the onset of upper GI symptoms was rapid; symptoms were reported by 19% of patients on the first day of the study, rising to 46% of patients at the end of the first week. Over the 3-month study period, 18% of patients were nonadherent to low-dose ASA treatment. The occurrence of upper GI symptoms negatively affected low-dose ASA adherence, in both the overall patient population (odds ratio [OR] = 0.84; 95% CI 0.70, 1.0) and among patients who were low-dose ASA naïve at baseline (OR = 0.76; 95% CI 0.57, 1.0). A total of 13% of patients discontinued low-dose ASA therapy. For the overall cohort and for the low-dose ASA-naïve patients at baseline, more than three episodes of upper GI symptoms during the previous week was associated with an increased risk of low-dose ASA discontinuation compared with no episodes of upper GI symptoms during the previous week (hazard ratio [HR] = 2.60; 95% CI 1.00, 6.80, and HR = 7.52; 95% CI 2.57, 22.04, respectively)., Conclusions: Upper GI symptoms can lead to nonadherence to, and discontinuation of, low-dose ASA CV-protective therapy. Patients who initiate low-dose ASA may experience an early onset of upper GI symptoms. (, Trial Registration Number: NCT00681759 [ClinicalTrials.gov Identifier]; AstraZeneca study code: D961FC00004).

Background: Low-dose acetylsalicylic acid (ASA; aspirin; 75-325 mg/day) is effective for the prevention of cardiovascular events, and its use in this indication is rapidly increasing. However, the use of ASA and, indeed, other non-steroidal anti-inflammatory drugs (NSAIDs) is limited by the incidence of adverse gastroduodenal events. OBJECTIVES AND SCOPE: To review the clinical evidence for, and the pharmacodynamic basis of, ASA-induced gastroduodenal toxicity in comparison with NSAIDs, and address the question of whether low-dose ASA is 'safe' from a gastroduodenal perspective. This was a narrative, descriptive review, rather than a formal systematic review., Findings: Adverse gastroduodenal effects, which are well known to occur with NSAIDs, are also prevalent in patients receiving low-dose ASA for cardiovascular protection even at doses as low as 75 mg/day. The risk of gastroduodenal toxicity is particularly high among 'at-risk' low-dose ASA patients (aged >70 years, previous ulcer or upper gastrointestinal bleeding and users of antiplatelets or NSAIDs). There are important differences in the mechanism of ASA-induced gastroduodenal toxicity, relative to NSAIDs. These differences include the effects on the cyclooxygenase (COX)-1 isoenzyme, local effects on the gastroduodenal mucosa specific to ASA and a reduction in platelet aggregation., Conclusion: Data suggest that ASA causes significant gastroduodenal damage even at the low doses used for cardiovascular protection. These effects (both systemic and possibly local) may be pharmacodynamically distinct from the gastroduodenal toxicity seen with NSAIDs. Studies are required to establish strategies for improving the tolerability of low-dose ASA, allowing patients to continue to benefit from the cardiovascular protection associated with such therapy.

Objective: To evaluate the effect of esomeprazole on the pharmacokinetics of low-dose acetylsalicylic acid (ASA) during repeated co-administration., Methods: This was an open, randomized, 3-way crossover study in 55 healthy volunteers. Treatment periods comprised 5 days' oral esomeprazole (40 mg) or ASA (325 mg) alone, or in combination, separated by washout of >or= 13 days. The primary pharmacokinetic end points were steady-state area under the concentration-time curve (AUCtau) and observed maximum plasma concentration (Cmax) of ASA +/- esomeprazole., Results: The estimates (90% confidence interval) of the geometric mean ratios for AUCtau and Cmax of ASA +/- esomeprazole were 1.04 (1.00 - 1.09) and 1.12 (1.03 - 1.22), respectively. Corresponding results for esomeprazole +/- ASA were 0.93 (0.89 - 0.98) and 0.96 (0.91 - 1.01), respectively. Administration of esomeprazole and ASA in combination was well tolerated., Conclusions: There was no pharmacokinetic interaction between esomeprazole (40 mg) and ASA (325 mg) during repeated co-administration in healthy volunteers.

Background and Objective: : As upper gastrointestinal (GI) symptoms are common with the use of low-dose aspirin (low-dose acetylsalicylic acid [LDASA]; 75-325 mg/day), this exploratory qualitative study evaluated the upper GI symptom experience and attribution of symptoms among patients taking LDASA for coronary artery disease (CAD) or known CAD risk factors., Methods: : Focus groups were conducted among patients aged ≥40 years with CAD or known CAD risk factors currently taking daily LDASA. Patients were recruited from primary-care clinical sites, and all had experienced upper GI symptoms the week before inclusion (including heartburn, acid reflux, and stomach or abdominal pain). The focus group discussions were designed to explore the participants' experience with upper GI symptoms, LDASA use, potential adverse effects of treatment, and physician interactions. Content analysis and descriptive statistics were used to analyze the data., Results: : Thirty-three men and women participated in four focus group sessions in France and in the US. All participants recognized the cardioprotective benefits of LDASA and reported a high level of compliance with therapy. Although participants regarded LDASA as a necessary and valuable treatment, many participants had concerns about LDASA use, primarily because of the bleeding risk. Many participants were aware that LDASA may cause GI symptoms. Participants experienced a range of upper GI symptoms, including heartburn, regurgitation, and nausea. Almost half of the participants believed that their GI symptoms were solely due to lifestyle issues such as stress and eating spicy food rather than being caused by medication, where others reported that they were directly related to LDASA use. The GI symptoms experienced by LDASA users were cited as troublesome, causing the participants to change eating habits, avoid stress or employ stress-reduction techniques, change physical activities, and take more medication to treat the symptoms., Conclusion: : Participants were well aware of the potential adverse effects of LDASA use and reported that GI symptoms had a high impact on several areas of their lives. To maintain the cardioprotective benefits of LDASA, participants used several strategies to deal with their upper GI symptoms, including changing their eating habits, avoiding stress, changing their physical activities, and taking medication.

Background and Objective: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for the treatment of pain in rheumatic disorders and chronic pain syndromes. Their use is, however, limited by gastrointestinal (GI) toxicity, including upper GI symptoms, ulcers and related complications. Using data from the NASA/SPACE studies, we have reviewed the efficacy and tolerability of esomeprazole (20 or 40 mg once daily) in the management (i.e. short-term resolution plus long-term prevention of relapse) of upper GI symptoms in users of continuous daily NSAIDs., Methods: The NASA/SPACE programme comprised four double-blind, placebo-controlled studies in NSAID users. Two studies evaluated the efficacy of esomeprazole for upper GI symptom relief over 4 weeks. Those patients with symptom relief were then enrolled into a further two studies that assessed efficacy over 6 months., Results: In the 4-week studies, more patients in the esomeprazole groups achieved relief from upper GI symptoms at week 4 compared with placebo (p<0.05). The proportion of patients with symptom relapse at 6 months was lower with esomeprazole 20 mg and 40 mg than with placebo (p

Objectives: To investigate the efficacy and safety of the 5-hydroxytrypamine 1A (5-HT(1A)) receptor antagonist AZD7371 tartrate monohydrate (robalzotan tartrate monohydrate), termed AZD7371 here, in patients with irritable bowel syndrome (IBS)., Methods: Patients meeting the Rome II criteria for IBS (N = 402) were randomized to treatment with AZD7371 20 mg or 5 mg or matching placebo tablets twice daily for 12 wk. The patients completed daily and weekly diary assessments, reporting abdominal discomfort or pain and description of bowel movements. They also completed validated symptom and quality-of-life questionnaires., Results: Neither AZD7371 regimen was significantly more effective than placebo in providing adequate relief from IBS symptoms in at least 2 out of 4 wk per month over the 12 wk of treatment. There was also no significant difference between the treatment groups and placebo in the change in score in the validated symptom and quality-of-life questionnaires. Overall, 22.1% of patients experienced adverse events (AEs) attributed to the study medication: 44 of 133 (33.1%) in the 20 mg AZD7371 group, 27 of 131 (20.6%) in the 5 mg AZD7371 group, and 17 of 134 (12.7%) in the placebo group. Also, 31 of 57 (54%) of AEs leading to discontinuation were central nervous system-related. Hallucinations or hallucination-like AEs were reported by eight patients taking AZD7371, and by none of the patients in the placebo group. After these events led to discontinuation in six patients, the study was prematurely terminated., Conclusions: In view of the AE profile and lack of efficacy in IBS, the clinical development of AZD7371 has been stopped.

Non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclo-oxygenase-2 (COX-2) inhibitors, cause upper gastrointestinal (GI) symptoms that are relieved by treatment with esomeprazole. We assessed esomeprazole for maintaining long-term relief of such symptoms. Six hundred and ten patients with a chronic condition requiring anti-inflammatory therapy who achieved relief of NSAID-associated symptoms of pain, discomfort, or burning in the upper abdomen during two previous studies were enrolled and randomly assigned into two identical, multicentre, parallel-group, placebo-controlled studies of esomeprazole 20 mg or 40 mg treatment (NASA2 [Nexium Anti-inflammatory Symptom Amelioration] and SPACE2 [Symptom Prevention by Acid Control with Esomeprazole] studies; ClinicalTrials.gov identifiers NCT00241514 and NCT00241553, respectively) performed at various rheumatology, gastroenterology, and primary care clinics. Four hundred and twenty-six patients completed the 6-month treatment period. The primary measure was the proportion of patients with relapse of upper GI symptoms, recorded in daily diary cards, after 6 months. Relapse was defined as moderate-to-severe upper GI symptoms (a score of more than or equal to 3 on a 7-grade scale) for 3 days or more in any 7-day period. Esomeprazole was significantly more effective than placebo in maintaining relief of upper GI symptoms throughout 6 months of treatment. Life-table estimates (95% confidence intervals) of the proportion of patients with relapse at 6 months (pooled population) were placebo, 39.1% (32.2% to 46.0%); esomeprazole 20 mg, 29.3% (22.3% to 36.2%) (p = 0.006 versus placebo); and esomeprazole 40 mg, 26.1% (19.4% to 32.9%) (p = 0.001 versus placebo). Patients on either non-selective NSAIDs or selective COX-2 inhibitors appeared to benefit. The frequency of adverse events was similar in the three groups. Esomeprazole maintains relief of NSAID-associated upper GI symptoms in patients taking continuous NSAIDs, including selective COX-2 inhibitors.