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

Abstract

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.

Conflict of interest statement

Competing interests: JMS—consultant: AstraZeneca, Novartis, Pfizer, Bayer, Takeda, Pozen, NiCox. Speaker's honoraria: AstraZeneca. PJD—AstraZeneca previously supplied the study drug for a large, international, investigator-initiated, Canadian Institutes of Health Research funded randomised, controlled trial (ie, the POISE-1 Trial). JH—no conflicts of interest declared. PHK—speaker for AstraZeneca, Nycomed and Janssen-Cilag. No stocks or shares or direct financial links. AL—adviser to AstraZeneca, Pfizer, Nicox, Bayer. Speaker: AstraZeneca, Pfizer. SVvZ—grant/research support and/or honoraria: Abbott, AstraZeneca, Janssen-Ortho, Nycomed and Takeda. EN, L-ES—employees: AstraZeneca.

Figures

Figure 1

Patient flow through the study. All randomised patients are included in the intention-to-treat (ITT) analyses, including those patients who did not complete 26 weeks of treatment. Lack of response was defined as development of gastric and/or duodenal ulcer and/or upper gastrointestinal symptoms requiring active intervention; the study-specific discontinuation criterion was defined as low-dose acetylsalicylic acid (ASA) treatment permanently stopped; severe non-compliance was defined as all other forms of non-compliance except stopping low-dose ASA treatment; safety reasons were defined as those to protect study subjects from potential safety risks—for example, new data causing study termination or subpopulation of subjects to be discontinued. All discontinuations were judged by the study investigators. aTwo patients had positive Helicobacter pylori status and ulcer at baseline endoscopy; bsix patients had Los Angeles(LA) grade C or D erosive (reflux) oesophagitis and ulcer at baseline endoscopy.

Figure 2

Cumulative percentage of patients with peptic ulcer(s) by week 26 (intention-to-treat population, Kaplan–Meier curve).