Impact of Acid Inhibition on Esophageal Mucosal Injury Induced by Low-Dose Aspirin

Abstract

Background and Aim: Aspirin enjoys widespread use as an antithrombotic drug, but such ubiquity also increases the risk of gastrointestinal mucosal injury. Recent studies have shown that aspirin can also induce esophageal mucosal injury. We resolved to determine the intragastric pH value necessary to prevent aspirin-induced esophageal mucosal injury. Methods: 15 healthyJapanese volunteers were dosed for 7 days in a four-way random crossover trial with 100 mg entero-coated type aspirin only once daily, 100 mg aspirin + 20 mg famotidine twice daily, 15 mg lansoprazole once daily, or 10 mg rabeprazole once daily. All subjects underwent endoscopy and intragastric pH monitoring on day 7. Results: 7 individuals (46.7%) developed esophageal mucosal injury when ingesting aspirin alone. The incidence of esophageal mucosal injury was reduced however with concomitant dosing of aspirin and famotidine (26.6%; p = 0.193), lansoprazole (0%; p = 0.004), and rabeprazole (6.7%; p = 0.019). Among individuals for whom mean 24-h pH was >5.0 and who experienced pH <4.0 less than 40% of the time, none developed aspirin-induced esophageal mucosal injury. Conclusion: Acid inhibition achieved with a half-dose of a proton pump inhibitor effectively prevented development of aspirin-induced esophageal mucosal injury, whereas a standard dose of a histamine-2-receptor antagonist failed to achieve the same results.

Antiplatelet Drugs Are a Risk Factor for Esophageal Mucosal Injury

“…LDA causes not only gastric mucosal injury, but also esophageal and small bowel mucosal injury [3,7]. In our study, esophageal and gastric mucosal lesions were observed in 52 and 93% volunteers, respectively, on LDA treatment for 7 days [4,5,6,7], suggesting that LDA may be a risk factor for esophageal mucosal injury.…”

“…Epidemiological studies of aspirin users to investigate relationship between the incidence of esophageal injury and LDA intake are limited in number [3,6,7,22,23,24,25,26,27,28], Lanas and Hirschowitz [22] were the first to demonstrate that 62% of GERD patients undergoing endoscopy were currently taking LDA, whereas only 26% of controls without GERD reported LDA use. Although half of the previous studies did not find a significant relationship with esophageal injury with mucosal break and LDA intake [23,24,25,26,28], there was no study which investigated risks for development of color changes without mucosal breaks at the EC junction.…”

“…Previously, there was no report showed intraesophageal pH on the development of LDA-induced esophageal damage [6,7]. Therefore, our aim was to clarify whether antiplatelet drug-induced esophageal injury depended on level of acid reflex to esophagus by using 24-hour intraesophageal and intragastric pH monitoring.…”

“…Low-dose aspirin (LDA) exerts an antiplatelet effect by decreasing the production of platelet thromboxane B2 via inhibition of cyclooxygenase-1 (COX-1), and inhibition of gastrointestinal mucosal COX-1 often causes gastric mucosal injury [3,4,5,6,7,8]. 10.7 and 63.1% of patients taking LDA showed endoscopic evidence of peptic ulcer and gastric erosions, respectively [9], and long-term LDA therapy significantly increases the incidence of gastrointestinal hemorrhage, which is not decreased by either a decrease in the LDA dose or by the use of enteric-coated LDA [8].…”

“…10.7 and 63.1% of patients taking LDA showed endoscopic evidence of peptic ulcer and gastric erosions, respectively [9], and long-term LDA therapy significantly increases the incidence of gastrointestinal hemorrhage, which is not decreased by either a decrease in the LDA dose or by the use of enteric-coated LDA [8]. LDA causes not only gastric mucosal injury, but also esophageal and small bowel mucosal injury [3,7]. In our study, esophageal and gastric mucosal lesions were observed in 52 and 93% volunteers, respectively, on LDA treatment for 7 days [4,5,6,7], suggesting that LDA may be a risk factor for esophageal mucosal injury.…”