# Association of Peptic Ulcer Disease and Gastrointestinal Hemorrhage With Long-Term Use of Antiplatelet and Anticoagulant Therapy in Patients With Ischemic Heart Disease

## TL;DR

This study shows that long-term use of blood-thinning drugs in heart disease patients increases the risk of stomach ulcers and bleeding, especially when multiple drugs are used together.

## Contribution

The study identifies combined antiplatelet and anticoagulant therapy as a significant risk factor for gastrointestinal complications in ischemic heart disease patients.

## Key findings

- 64 out of 210 patients (30.5%) had peptic ulcer disease.
- Combined antiplatelet and anticoagulant therapy was associated with the highest rate of GI hemorrhage (45%).
- NSAID use and prior ulcer history were strong predictors of gastrointestinal bleeding.

## Abstract

Background and aim

Antiplatelet and anticoagulant therapies are essential in the long-term management of ischemic heart disease (IHD). However, their use is associated with increased gastrointestinal (GI) complications, particularly peptic ulcer disease (PUD) and hemorrhage. The aim of the study was to determine the association of peptic ulcer disease and gastrointestinal hemorrhage with long-term use of antiplatelet and anticoagulant therapy in patients with ischemic heart disease.

Methodology

This was a cross-sectional analytical study conducted at a tertiary care hospital in Azad Kashmir, Pakistan, from June 2024 to May 2025. A total of 210 patients receiving antiplatelet and/or anticoagulant therapy for at least six months were enrolled. Data on demographics, comorbidities, therapy category (single, dual, or combined antiplatelet-anticoagulant therapy), drug types, dosages, adherence, nonsteroidal anti-inflammatory drug (NSAID) exposure, H. pylori status, smoking, alcohol intake, proton pump inhibitors (PPI) use, and renal/hepatic disease were collected to assess potential confounders. Only patients presenting with upper GI symptoms or suspected bleeding were referred for endoscopy; thus, asymptomatic PUD may be underestimated. Endoscopic evaluations followed standardized criteria: PUD was diagnosed based on mucosal ulceration ≥5 mm, and hemorrhage severity was classified using the Forrest criteria. Missing data were minimized through direct patient interviews; when unavoidable, listwise deletion was applied. No sensitivity analyses were performed.

Results

Out of 210 patients, 64 (30.5%) were diagnosed with peptic ulcer disease, and 49 (23.3%) developed GI hemorrhage. The highest bleeding frequency was observed in patients receiving combined antiplatelet and anticoagulant therapy (45%, n=18), compared with dual antiplatelet therapy (21.9%, n=23) and single antiplatelet therapy (12.3%, n=8; p<0.01). Logistic regression identified prior ulcer history (OR: 2.6, 95% CI: 1.3-5.1, p=0.004), NSAID use (OR: 3.1, 95% CI: 1.5-6.4, p=0.002), and combined therapy (OR: 4.2, 95% CI: 2.1-8.4, p<0.001) as independent predictors of GI hemorrhage.

Conclusion

Long-term antiplatelet and anticoagulant therapy in patients with IHD is strongly associated with an increased risk of peptic ulcer disease and gastrointestinal hemorrhage, particularly in those receiving combined regimens. Prior ulcer history and NSAID use significantly elevate bleeding risk.