Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 28, 2016; 22(48): 10477-10481
Published online Dec 28, 2016. doi: 10.3748/wjg.v22.i48.10477
Protons pump inhibitor treatment and lower gastrointestinal bleeding: Balancing risks and benefits
Alberto Lué, Angel Lanas
Alberto Lué, Angel Lanas, Digestive Diseases Service, University Clinic Hospital Lozano Blesa, Avenida San Juan Bosco, 50009 Zaragoza, Spain
Alberto Lué, Angel Lanas, IIS Aragon, Avenida San Juan Bosco, 50009 Zaragoza, Spain
Angel Lanas, University of Zaragoza, Calle de Pedro Cerbuna, 50009 Zaragoza, Spain
Angel Lanas, CIBERehd, Av. Monforte de Lemos, 28029 Madrid, Spain
Author contributions: Lué A and Lanas A contributed to this paper.
Conflict-of-interest statement: Lué A and Lanas A declare no conflict of interest related to this publication.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Angel Lanas, MD, DSc, Professor, Chairman, Digestive Diseases Service, University Clinic Hospital Lozano Blesa, Avenida San Juan Bosco, 50009 Zaragoza, Spain. alanas@unizar.es
Telephone: +34-97-6768886 Fax: +34-97-6768846
Received: August 27, 2016
Peer-review started: August 31, 2016
First decision: September 20, 2016
Revised: September 28, 2016
Accepted: November 12, 2016
Article in press: November 13, 2016
Published online: December 28, 2016

Proton pump inhibitors (PPIs) represent a milestone in the treatment of acid-related diseases, and are the mainstay in preventing upper gastrointestinal bleeding in high-risk patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin. However, this beneficial effect does not extend to the lower gastrointestinal tract. PPIs do not prevent NSAID or aspirin-associated lower gastrointestinal bleeding (LGB). PPIs may increase both small bowel injury related to NSAIDs and low-dose aspirin treatment and the risk of LGB. Recent studies suggested that altering intestinal microbiota by PPIs may be involved in the pathogenesis of NSAID-enteropathy. An increase in LGB hospitalization rates may occur more frequently in older patients with more comorbidities and are associated with high hospital resource utilization, longer hospitalization, and increased mortality. Preventive strategies for NSAID and aspirin-associated gastrointestinal bleeding should be directed toward preventing both upper and lower gastrointestinal damage. Future research should be directed toward identifying patients at low-risk for gastrointestinal events associated with the use of NSAIDs or aspirin to avoid inappropriate PPI prescribing. Alternatively, the efficacy of new pharmacologic strategies should be evaluated in high-risk groups, with the aim of reducing the risk of both upper and lower gastrointestinal bleeding in these patients.

Keywords: Proton pump inhibitor, Small bowel, Small bowel, Lower gastrointestinal bleeding, Nonsteroidal anti-inflammatory drugs

Core tip: Proton pump inhibitors (PPIs) reduce the risk of upper, but not lower gastrointestinal bleeding (LGB) in patients receiving nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin. PPIs could exacerbate small bowel damage related to NSAIDs and low-dose aspirin, which contributes to an increased risk of LGB possibly related to pathological modifications of small bowel microbiota. LGB is a life-threatening condition, especially in older patients with comorbidities treated with NSAIDs, aspirin, or anticoagulants. No accepted treatments exist for decreasing the risk of LGB in these patients. Future research is needed on reducing inappropriate PPI use and evaluating possible pharmacologic interventions to decrease the risk of gastrointestinal bleeding.