Randomized, multicenter study: on-demand versus continuous maintenance treatment with esomeprazole in patients with non-erosive gastroesophageal reflux disease.

BACKGROUND: Most patients with gastroesophageal reflux disease experience symptomatic relapse after stopping acid-suppressive medication. The aim of this study was to compare willingness to continue treatment with esomeprazole on-demand versus continuous maintenance therapy for symptom control in patients with non-erosive reflux disease (NERD) after 6 months. METHODS: This multicenter, open-label, randomized, parallel-group study enrolled adults with NERD who were heartburn-free after 4 weeks' treatment with esomeprazole 20 mg daily. Patients received esomeprazole 20 mg daily continuously or on-demand for 6 months. The primary variable was discontinuation due to unsatisfactory treatment. On-demand treatment was considered non-inferior if the upper limit of the one-sided 95 % confidence interval (CI) for the difference between treatments was <10 %. RESULTS: Of 877 patients enrolled, 598 were randomized to maintenance treatment (continuous: n = 297; on-demand: n = 301). Discontinuation due to unsatisfactory treatment was 6.3 % for on-demand and 9.8 % for continuous treatment (difference -3.5 % [90 % CI: -7.1 %, 0.2 %]). In total, 82.1 and 86.2 % of patients taking on-demand and continuous therapy, respectively, were satisfied with the treatment of heartburn and regurgitation symptoms, a secondary variable (P = NS). Mean study drug consumption was 0.41 and 0.91 tablets/day, respectively. Overall, 5 % of the on-demand group developed reflux esophagitis versus none in the continuous group (P < 0.0001). The Gastrointestinal Symptom Rating Scale Reflux dimension was also improved for continuous versus on-demand treatment. Esomeprazole was well tolerated. CONCLUSIONS: In terms of willingness to continue treatment, on-demand treatment with esomeprazole 20 mg was non-inferior to continuous maintenance treatment and reduced medication usage in patients with NERD who had achieved symptom control with initial esomeprazole treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier (NCT number): NCT02670642 ; Date of registration: December 2015.

Esomeprazole for prevention and resolution of upper gastrointestinal symptoms in patients treated with low-dose acetylsalicylic acid for cardiovascular protection: the OBERON trial.

Although low-dose acetylsalicylic acid (ASA) is recommended for prevention of cardiovascular events in at-risk patients, its long-term use can be associated with the risk of peptic ulcer and upper gastrointestinal (GI) symptoms that may impact treatment compliance. This prespecified secondary analysis of the OBERON study (NCT00441727) determined the efficacy of esomeprazole for prevention/resolution of low-dose ASA-associated upper GI symptoms. A post hoc analysis of predictors of symptom prevention/resolution was also conducted. Helicobacter pylori-negative patients taking low-dose ASA (75-325 mg) for cardiovascular protection who had ≥1 upper GI risk factor were eligible. The patients were randomized to once-daily esomeprazole 40 mg, 20 mg, or placebo, for 26 weeks; 2303 patients (mean age 67.6 years; 36% aged >70 years) were evaluable for upper GI symptoms. The proportion of patients with dyspeptic or reflux symptoms (self-reported Reflux Disease Questionnaire) was significantly lower (P < 0.0001) in those treated with esomeprazole versus in those treated with placebo. Treatment with esomeprazole (P < 0.0001), age >70 years (P < 0.01), and the absence of upper GI symptoms at baseline (P < 0.0001) were all factors associated with prevention/resolution of upper GI symptoms. Together, these analyses demonstrate that esomeprazole is effective in preventing and resolving patient-reported upper GI symptoms in low-dose ASA users at increased GI risk.

Impact of gastrointestinal problems on adherence to low-dose acetylsalicylic Acid: a quantitative study in patients with cardiovascular risk.

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.

Prevention of peptic ulcers with esomeprazole in patients at risk of ulcer development treated with low-dose acetylsalicylic acid: a randomised, controlled trial (OBERON).

OBJECTIVE: To determine whether once-daily esomeprazole 40 mg or 20 mg compared with placebo reduces the incidence of peptic ulcers over 26 weeks of treatment in patients taking low-dose acetylsalicylic acid (ASA) and who are at risk for ulcer development. DESIGN: Multinational, randomised, blinded, parallel-group, placebo-controlled trial. SETTING: Cardiology, primary care and gastroenterology centres (n=240). PATIENTS: Helicobacter pylori-negative patients taking daily low-dose ASA (75-325 mg), who fulfilled one or more of the following criteria: age ≥18 years with history of uncomplicated peptic ulcer; age ≥60 years with either stable coronary artery disease, upper gastrointestinal symptoms and five or more gastric/duodenal erosions, or low-dose ASA treatment initiated within 1 month of randomisation; or age ≥65 years. All patients were ulcer-free at study entry. INTERVENTIONS: Once-daily, blinded treatment with esomeprazole 40 mg, 20 mg or placebo for 26 weeks. MAIN OUTCOME MEASURES: The primary end point was the occurrence of endoscopy-confirmed peptic ulcer over 26 weeks. RESULTS: A total of 2426 patients (52% men; mean age 68 years) were randomised. After 26 weeks, esomeprazole 40 mg and 20 mg significantly reduced the cumulative proportion of patients developing peptic ulcers; 1.5% of esomeprazole 40 mg and 1.1% of esomeprazole 20 mg recipients, compared with 7.4% of placebo recipients, developed peptic ulcers (both p<0.0001 vs placebo). Esomeprazole was generally well tolerated. Conclusions Acid-suppressive treatment with once-daily esomeprazole 40 mg or 20 mg reduces the occurrence of peptic ulcers in patients at risk for ulcer development who are taking low-dose ASA. Clinical trial registration number ClinicalTrials.gov identifier: NCT00441727.

Esomeprazole for the management of upper gastrointestinal symptoms in patients who require NSAIDs: a review of the NASA and SPACE double-blind, placebo-controlled studies.

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

Efficacy of esomeprazole (20 mg once daily) for reducing the risk of gastroduodenal ulcers associated with continuous use of low-dose aspirin.

OBJECTIVES: Low-dose aspirin is standard treatment for prevention of cardiovascular events in at-risk patients. However, long-term administration of low-dose aspirin is associated with a greater risk of adverse events, including gastroduodenal ulcers. This study determined the efficacy of esomeprazole for reducing the risk of gastric and/or duodenal ulcers and dyspeptic symptoms in patients receiving continuous, low-dose aspirin therapy. METHODS: Patients aged > or =60 yr, without baseline gastroduodenal ulcer at endoscopy, who were receiving aspirin 75-325 mg once daily, were randomized to esomeprazole 20 mg once daily or placebo for 26 wk. The presence of endoscopic gastric and/or duodenal ulcers and esophageal lesions was assessed at weeks 8 and 26. Upper gastrointestinal symptoms were assessed at weeks 8, 16, and 26. RESULTS: The intention-to-treat population comprised 991 patients (esomeprazole, N = 493; placebo, N = 498). Twenty-seven patients (5.4%) in the placebo group developed a gastric or duodenal ulcer during 26 weeks' treatment compared with eight patients (1.6%) in the esomeprazole group (life-table estimates: 6.2%vs 1.8%; P= 0.0007). At 26 wk, the cumulative proportion of patients with erosive esophagitis was significantly lower for esomeprazole versus placebo (4.4% and 18.3%, respectively; P < 0.0001). At 26 wk, esomeprazole-treated patients were more likely to experience resolution of heartburn, acid regurgitation, and epigastric pain (P < 0.05). CONCLUSIONS: Esomeprazole 20 mg once daily reduces the risk of developing gastric and/or duodenal ulcers and symptoms associated with the continuous use of low-dose aspirin in patients aged > or =60 yr without preexisting gastroduodenal ulcers.

Esomeprazole 40 mg administered intravenously has similar safety and efficacy profiles to the oral formulation in patients with erosive esophagitis.

BACKGROUND/AIMS: An intravenous formulation of esomeprazole has been developed for use in patients where oral administration is not appropriate. This study evaluated safety after 1 and 4 weeks, and efficacy after 4 weeks' esomeprazole 40 mg once daily treatment, administered via an intravenous injection, intravenous infusion or orally, in patients with erosive esophagitis. METHODS: In this double-blind, multi-centre study, patients with endoscopically confirmed erosive esophagitis (Los Angeles grade A-D) were randomized to receive 1 week's treatment of esomeprazole 40 mg once daily, via a 3-min injection, a 30-min infusion or orally, followed by 3 weeks of open treatment with oral esomeprazole 40 mg once daily. Safety variables were evaluated following 1 and 4 weeks' esomeprazole treatment. Healing rates at 4 weeks were estimated. RESULTS: Intravenous and oral esomeprazole were equally well tolerated during the first week, and after 4 weeks' treatment. The 3 treatment groups showed similar levels of healing following 4 weeks' treatment with esomeprazole (injection + oral: 79.7%; infusion + oral: 80.2%; oral alone: 82.6%). CONCLUSIONS: Esomeprazole 40 mg administered via an intravenous injection, intravenous infusion or orally administered for 1 week, followed by 3 weeks of oral dosing, is well tolerated and provides effective healing of erosive esophagitis.

Clopidogrel and warfarin: absence of interaction in patients receiving long-term anticoagulant therapy for non-valvular atrial fibrillation.

The effect of concomitantly administered clopidogrel on anti-coagulation status was investigated in patients receiving long-term warfarin therapy. Forty-three patients with non-valvular atrial fibrillation who were receiving long-term warfarin and had a stable international normalized ratio (INR) between 2 and 3 were randomly assigned to clopidogrel 75 mg daily or placebo for 8 days (Days 1-8). INR (primary endpoint) and plasma levels of warfarin enantiomers (secondary endpoint) were evaluated at Days 3, 6, 9, 13 and 22. Mean INR remained extremely stable in the clopidogrel group, the maximum percentage change from baseline being 0.6% at Day 6. Plasma levels of R- and S-warfarin also remained very stable in those receiving clopidogrel. No serious adverse events, premature discontinuations of study drug or bleeding occurred with clopidogrel. In conclusion, the stable anticoagulation status of patients receiving long-term warfarin therapy is unaffected by concomitant administration of clopidogrel 75 mg daily.