Association between eupatilin and reduction in small bowel bleeding in aspirin users and aspirin plus acid suppressant users

Abstract

Background/aims: Capsule endoscopy (CE) has shown that low-dose aspirin occasionally causes small bowel (SB) bleeding. We herein evaluated the protective effects of mucoprotective agents (MPAs) on SB bleeding in aspirin users using the nationwide database of claims data from the National Health Insurance Service (NHIS).

Methods: As CE is an insured procedure, we constructed an aspirin-SB cohort using NHIS claims data, with a maximum follow- up period of 24 months. Patients with anemia, melena, or hematochezia that occurred within 4 weeks before and after performing CE were suspected to have SB bleeding. A Cox proportional hazards regression model was used to determine the risk factors for SB bleeding. Subgroup analyses were conducted among patients who used acid suppressants, such as proton pump inhibitors (PPIs) and histamine-2 receptor antagonists.

Results: A total of 15,542 aspirin users were included. Anticoagulant use (hazard ratio [HR], 3.22), high Charlson comorbidity index score (≥ 2) (HR, 3.54), and PPI use (HR, 2.85) were significantly associated with SB bleeding, whereas eupatilin use (HR, 0.35) was a preventive factor. SB bleeding occurred more frequently in concurrent users of acid suppressants than in nonusers (1.3% vs. 0.5%). Subgroup analysis revealed that eupatilin significantly reduced the risk of SB bleeding in aspirin users with concurrent use of acid suppressants (HR, 0.23 vs. 2.55).

Conclusion: Eupatilin was associated with a reduced risk of SB bleeding in both aspirin users and those with concomitant use of acid suppressants. Eupatilin use should be considered for aspirin users, especially for those concomitantly taking acid suppressants.

Keywords: Anti-ulcer agents; Aspirin; Capsule endoscopy; Eupatilin; Gastrointestinal hemorrhage.

Figure 1

Flow diagram summarizing the general population-based aspirin/NSAID-SB cohort construction to investigate aspirin-induced SB bleeding. NSAID, nonsteroidal anti-inflammatory drug; SB, small bowel; NHIS, National Health Insurance Service; CE, capsule endoscopy.

Figure 2

Schematic diagram depicting the typical follow-up period for aspirin users, observed for up to 24 months.

Figure 3

Kaplan-Meier curve illustrating the cumulative incidence of small bowel bleeding based on the concurrent use of acid suppressants (proton pump inhibitor or histamine-2 receptor antagonist) and mucoprotective agents in aspirin users. None, aspirin users without concurrent use of gastrointestinal drugs; Acid suppressants only, aspirin plus acid suppressants; Acid suppressants + eupatilin, aspirin plus acid suppressants and eupatilin; Acid suppressants + rebamipide, aspirin plus acid suppressants and rebamipide; Acid suppressants + other MPAs, aspirin plus acid suppressants and other mucoprotective agents.