Retrospective Cohort Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 14, 2018; 24(34): 3908-3918
Published online Sep 14, 2018. doi: 10.3748/wjg.v24.i34.3908
Gastroduodenal ulcer bleeding in elderly patients on low dose aspirin therapy
Koh Fukushi, Keiichi Tominaga, Kazunori Nagashima, Akira Kanamori, Naoya Izawa, Mimari Kanazawa, Takako Sasai, Hideyuki Hiraishi
Koh Fukushi, Keiichi Tominaga, Kazunori Nagashima, Akira Kanamori, Naoya Izawa, Mimari Kanazawa, Hideyuki Hiraishi, Department of Gastroenterology, Dokkyo Medical University, Tochigi 3210293, Japan
Takako Sasai, Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, Okayama 700850, Japan
Author contributions: All authors contributed to this research study; Fukushi K contributed to manusucript writing, performing procedures and data analysis; Tominaga K, Sasai T and Hiraishi H contributed to draft conception and design; Nagashima K contributed to data analysis; Nagashima K, Kanamori A, Izawa N and Kanazawa M contributed to writing the manuscript.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of the Dokkyo Medical University.
Informed consent statement: Patients were not required to give informed consent to this study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: All authors declare no conflicts-of-interest related to this article.
Data sharing statement: No additional data are available.
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:
Correspondence to: Keiichi Tominaga, MD, PhD, Doctor, Department of Gastroenterology, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Shimotuga, Tochigi 3210293, Japan.
Telephone: +81-282-872147 Fax: +81-282-867761
Received: April 4, 2018
Peer-review started: April 4, 2018
First decision: May 29, 2018
Revised: July 12, 2018
Accepted: July 22, 2018
Article in press: July 21, 2018
Published online: September 14, 2018
Research background

As the Japanese population ages, the prevalence of cerebrovascular disorders and ischemic heart diseases have been increasing. Under these circumstances, low-dose aspirin (LDA) has increasingly been used for secondary prevention of such conditions in recent years. Severe adverse reactions to LDA include hemorrhagic gastroduodenal ulcer. In the future, the incidences of LDA-induced peptic ulcer and ulcer hemorrhage are expected to rise in the elderly.

Research motivation

As previously reported, the concomitant use of LDA and other antithrombotic drugs increases the risk of ulcer hemorrhage. However, no report of any study that LDA-induced ulcer hemorrhage in elderly patients who expected to become severe. Elucidation of the current status of this condition would thus be useful.

Research objectives

Of patients with hemorrhagic gastroduodenal ulcer caused by oral administration of antithrombotic drugs, those receiving oral LDA, which is likely to be particularly problematic, were targeted. By comparing elderly and non-elderly patients, this study aimed to identify clinical features of the ulcer and factors contributing to its progression to severe conditions. These issues are particularly important in countries that have become aged societies, like Japan, or are aging at a rapid rate.

Research methods

This study included 1105 patients with hemorrhagic gastroduodenal ulcer, who were divided according age (the elderly group consisting of those 70 years of age or older and the non-elderly group consisting of those less than 70 years of age) and orally administered drugs (the LDA monotherapy group and the LDA combination therapy group). We retrospectively compared and analyzed the length of hospital stay, presence or absence of decreased hemoglobin (Hb) level, use of blood transfusion, rate of severe conditions, etc.

Research results

When elderly patients were compared between the LDA monotherapy and LDA combination therapy groups, the rate of severe conditions was higher in the LDA combination therapy group. Concomitant use of LDA with antithrombotic drugs or nonsteroidal anti-inflammatory drugs was found to contribute to the progression of severe hemorrhagic gastroduodenal ulcer to severe conditions. Moreover, among the LDA monotherapy group, no significant difference in the rate of severe conditions was observed between elderly and non-elderly patients. Oral administration of LDA alone was not found to be a risk factor for progression to severe conditions in elderly patients.

Research conclusions

This study showed that LDA combination therapy contributes to progression to severe conditions, such as markedly decreased Hb levels, increased frequency of blood transfusion, and prolonged hospital stay, in elderly patients. Meanwhile, in cases receiving LDA monotherapy, advanced age is not a risk factor for progression to severe conditions. Based on these findings, when LDA combination therapy is administered to elderly patients, efforts should be made toward adequate prevention of hemorrhage. In cases with ulcer hemorrhage, while treatment is given, appropriate antithrombotic therapy is required to prevent the occurrence of vascular events. Furthermore, apparently, if LDA monotherapy is administered, even elderly patients may be at a risk of progression to severe conditions similar to that in non-elderly patients.

Research perspectives

The limitations of this study include the single-center retrospective design. In addition, because the analysis in the LDA combination therapy group was not stratified according to the types of antithrombotic drugs used in combination with LDA, the effects of different combinations of drugs on the risk of hemorrhage should be examined in future studies. Although the use of proton pump inhibitors (PPIs) is preferable for prevention of hemorrhage as described in the guidelines, further accumulation of additional data and studies on effects, adverse events, etc. are needed to use PPIs appropriately. Furthermore, evidence must be accumulated for the prophylactic effect of novel therapeutic drugs, such as vonoprazan, for ulcers in elderly patients.