In this editorial we comment on the article by Fukushi K et al published in the recent issue of the World Journal of Gastroenterology 2018; 24(34): 3908-3918. We focus specifically on the mechanisms of the anti-thrombotic action of
aspirin, gastric mucosal injury and aging-related increased susceptibility of gastric mucosa to injury.
Aspirin is widely used not only for the management of acute and
chronic pain and
arthritis, but also importantly for the primary and
secondary prevention of cardiovascular events such as
myocardial infarcts and
strokes. Clinical trials have consistently shown that antiplatelet
therapy with long term, low dose
aspirin (LDA) - 75 to 325 mg daily, dramatically reduces the risk of non-fatal
myocardial infarcts,
stroke and mortality in patients with established arterial diseases. However, such treatment considerably increases the risk of gastrointestinal (GI) ulcerations and serious
bleeding by > 2-4 fold, especially in aging individuals. This risk is further increased in patients using LDA together with other
antiplatelet agents, other
nonsteroidal anti-inflammatory agents (
NSAIDs) and/or alcohol, or in patients with Helicobacter pylori (H. pylori)
infection. Previous studies by our group and others have demonstrated prominent structural and functional abnormalities in gastric mucosa of aging individuals (which we refer to as aging gastric mucosa or "aging gastropathy") compared to the gastric mucosa of younger individuals. Aging gastric mucosa has impaired mucosal defense, increased susceptibility to injury by a variety of noxious agents such as
aspirin, other
NSAIDs and
ethanol, and delayed and impaired healing of injury. The mechanism underlying these abnormalities of aging gastric mucosa include reduced mucosal blood flow causing
hypoxia, upregulation of PTEN, activation of pro-apoptotic
caspase-3 and
caspase-9, and reduced
survivin (anti-apoptosis
protein),
importin-α (nuclear transport
protein),
vascular endothelial growth factor, and
nerve growth factor. The decision regarding initiation of a long-term LDA
therapy should be made after a careful consideration of both cardiovascular and GI risk factors. The latter include a previous history of GI
bleeding and/or
ulcers, age ≥ 70, male gender, concurrent use of other
NSAIDs, alcohol consumption and H. pylori
infection. Furthermore, the incidence of GI
ulcers and
bleeding can be reduced in patients on long term LDA treatment by several measures. Clinicians treating such patients should test for and eradicate H. pylori, instruct patients to avoid alcohol and non-
aspirin NSAIDs, including cyclooxygenase-2-selective
NSAIDs, and prescribe
proton pump inhibitors in patients on LDA
therapy. In the future, clinicians may be able to prescribe one of several potential new drugs, which include
aspirin associated with
phosphatidylcholine (
PL2200), which retains all property of
aspirin but reduces by approximately 50% LDA-induced GI ulcerations.