Joseph J.Y. Sung, MD; Alan Barkun, MD; Ernst J. Kuipers, MD; Joachim Mössner, MD; Dennis M. Jensen, MD; Robert Stuart, MD; James Y. Lau, MD; Henrik Ahlbom, BSc; Jan Kilhamn, MD; Tore Lind, MD; Peptic Ulcer Bleed Study Group
Use of proton-pump inhibitors in the management of peptic ulcer bleeding is controversial because discrepant results have been reported in different ethnic groups.
To determine whether intravenous esomeprazole prevents recurrent peptic ulcer bleeding better than placebo in a multiethnic patient sample.
Randomized trial conducted between October 2005 and December 2007; patients, providers, and researchers were blinded to group assignment.
91 hospital emergency departments in 16 countries.
Patients 18 years or older with peptic ulcer bleeding from a single gastric or duodenal ulcer showing high-risk stigmata.
Intravenous esomeprazole bolus, 80 mg, followed by 8-mg/h infusion, over 72 hours or matching placebo, each given after successful endoscopic hemostasis. Intervention was allocated by computer-generated randomization. After infusion, both groups received oral esomeprazole, 40 mg/d, for 27 days.
The primary end point was rate of clinically significant recurrent bleeding within 72 hours. Recurrent bleeding within 7 and 30 days, death, surgery, endoscopic re-treatment, blood transfusions, hospitalization, and safety were also assessed.
Of 767 patients randomly assigned, 764 provided data for an intention-to-treat analysis (375 esomeprazole recipients and 389 placebo recipients). Fewer patients receiving intravenous esomeprazole (22 of 375) had recurrent bleeding within 72 hours than those receiving placebo (40 of 389) (5.9% vs. 10.3%; difference, 4.4 percentage points [95% CI, 0.6% to 8.3%]; P = 0.026). The difference in bleeding recurrence remained significant at 7 days and 30 days (P = 0.010). Esomeprazole also reduced endoscopic re-treatment (6.4% vs. 11.6%; difference, 5.2 percentage points [95% CI of difference, 1.1 percentage points to 9.2 percentage points]; P = 0.012), surgery (2.7% vs. 5.4%), and all-cause mortality rates (0.8% vs. 2.1%) more than placebo, although differences for the latter 2 comparisons were not significant. About 10% and 40% of patients in both groups reported serious and nonserious adverse events, respectively.
Endoscopic therapy was not completely standardized; some patients received epinephrine injection, thermal coagulation, or hemoclips alone, whereas others received combination therapy, but there were similar proportions with single therapy in each group.
High-dose intravenous esomeprazole given after successful endoscopic therapy to patients with high-risk peptic ulcer bleeding reduced recurrent bleeding at 72 hours and had sustained clinical benefits for up to 30 days.
AstraZeneca Research and Development.
Whether profound acid suppression with high-dose proton-pump inhibitors improves outcomes in patients with peptic bleeding ulcers is unclear.
This multicenter trial included 764 adults with a single bleeding gastric or duodenal ulcer that had high-risk stigmata. All had successful endoscopic hemostasis and were randomly assigned to intravenous high-dose esomeprazole or matching placebo for 72 hours. Fewer esomeprazole recipients than placebo recipients experienced recurrent bleeding (5.9% vs. 10.3%) or needed endoscopic re-treatment (6.4% vs. 11.6%).
High-dose esomeprazole, given after successful endoscopic treatment, reduced recurrent bleeding in patients with high-risk peptic ulcer bleeding.
GI = gastrointestinal; ITT = intention-to-treat; PP = per-protocol.
The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.
Sung JJ, Barkun A, Kuipers EJ, Mössner J, Jensen DM, Stuart R, et al. Intravenous Esomeprazole for Prevention of Recurrent Peptic Ulcer Bleeding: A Randomized Trial. Ann Intern Med. 2009;150:455–464. doi: 10.7326/0003-4819-150-7-200904070-00105
Download citation file:
Published: Ann Intern Med. 2009;150(7):455-464.
Gastroenterology/Hepatology, Peptic Disease, Peptic Ulcer.
Copyright © 2018 American College of Physicians. All Rights Reserved.
Print ISSN: 0003-4819 | Online ISSN: 1539-3704
Conditions of Use