An extended 36-week oral esomeprazole improved long-term recurrent peptic ulcer bleeding in patients at high risk of rebleeding

Hsueh-Chien Chiang, Er-Hsiang Yang, Huang-Ming Hu, Wei-Ying Chen, Wei-Lun Chang, Chung-Tai Wu, Deng-Chyang Wu, Bor-Shyang Sheu, Hsiu-Chi Cheng, Hsueh-Chien Chiang, Er-Hsiang Yang, Huang-Ming Hu, Wei-Ying Chen, Wei-Lun Chang, Chung-Tai Wu, Deng-Chyang Wu, Bor-Shyang Sheu, Hsiu-Chi Cheng

Abstract

Background: Patients with Rockall scores ≥6 have an increased risk of long-term peptic ulcer rebleeding. This study was aimed toward investigating whether an extended course of oral esomeprazole up to 1 year decreased ulcer rebleeding in such patients.

Methods: We prospectively enrolled 120 patients with peptic ulcer bleeding and Rockall scores ≥6. After an initial 16-week oral proton pump inhibitor (PPI) treatment, patients were randomized to receive a 36-week course of oral twice-daily esomeprazole 20 mg (Group D, n = 60) or once-daily (Group S, n = 60). Thereafter, they were divided into the PPI-on-demand (n = 32) and PPI-discontinued (n = 77) subgroups. Our previous cohort with Rockall scores ≥6 served as the controls (Group C, n = 135); they received only an initial 8- to 16-week oral PPI. The primary and secondary outcomes were peptic ulcer rebleeding during the first year and the second year-and-thereafter, respectively.

Results: For the primary outcome, groups D and S comprised a higher proportion of rebleeding-free than Group C (P = 0.008 and 0.03, log-rank test). The competing-risks regression analysis confirmed that extended PPI use and American Society of Anesthesiologists classification were independent factors contributing to the primary outcome. For the secondary outcome, PPI-on-demand had a borderline higher proportion of rebleeding-free than Group C (P = 0.07, log-rank test); however, only the Rockall score was the independent factor.

Conclusions: An extended 36-week course of oral esomeprazole 20 mg, twice- or once-daily for patients with Rockall scores ≥6 reduced ulcer rebleeding during the first year, but the effect needed to be further validated when PPIs were shifted to on-demand or discontinued thereafter (NCT02456012, 28/05/2015).

Keywords: Duodenal ulcer; Peptic ulcer hemorrhage; Proton pump inhibitors; Risk scores; Stomach ulcer.

Conflict of interest statement

The authors declare neither financial nor non-financial relationship with any company involved in this study. There is no conflict of interest involved in this submission.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Trial profile
Fig. 2
Fig. 2
The cumulative rebleeding-free proportion during the first year. The Kaplan-Meier curves show that the cumulative proportions of patients who were bleeding-free during the first year were higher in Group D than in Group C and higher in Group S than in Group C (P = 0.008 and 0.03, log-rank test, respectively), but were not significantly different between Group D and Group S (P = 0.32, log-rank test)
Fig. 3
Fig. 3
The cumulative rebleeding-free proportion during the second year-and-thereafter. The Kaplan-Meier curves show that the cumulative proportion of patients who were bleeding-free during the second year-and-thereafter was borderline higher in the PPI-on-demand subgroup as compared with those in the PPI-discontinued subgroup (P = 0.06, log-rank test) and in Group C (P = 0.07, log-rank test). However, the cumulative proportion of recurrent bleeding-free patients was not significantly different between the PPI-discontinued subgroup and Group C (P = 0.97, log-rank test). Abbreviations: PPI, proton pump inhibitor

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