Mechanisms of the Development of Aspirin-Induced Gastroduodenopathies in Patients with Ischemic Heart Disease during Acetylsalicylic Acid Therapy

Abstract

Aspirin (acetylsalicylic acid, ASA) remains the cornerstone of antiplatelet therapy for secondary prevention in ischemic heart disease (IHD); however, its chronic use is frequently associated with gastrointestinal (GI) complications, collectively known as aspirin-induced gastroduodenopathies. The ulcerogenic effect of ASA is multifactorial and primarily determined by inhibition of cyclooxygenase-1 (COX-1) with subsequent suppression of protective prostaglandins (PGE₂, PGI₂), direct topical mucosal injury, and activation of inflammatory and oxidative pathways. ASA disrupts the balance between mucosal protective and aggressive factors at all levels of the intestinal barrier, leading to epithelial injury, increased permeability, microvascular ischemia, and impaired mucosal repair. Experimental data demonstrate that ASA shifts arachidonic acid metabolism toward the lipoxygenase pathway, resulting in elevated leukotriene B4 and tumor necrosis factor-alpha (TNF-α), promoting neutrophil adhesion, oxidative stress, and epithelial apoptosis. In patients with IHD, pre-existing endothelial dysfunction, reduced mucosal perfusion, and concomitant risk factors (advanced age, H. pylori infection, use of anticoagulants or corticosteroids) exacerbate mucosal vulnerability. Preventive strategies include acid suppression with proton pump inhibitors, mucoprotective agents, eradication of H. pylori, and cautious selection of antiplatelet regimens. Understanding the underlying mechanisms of ASA-induced mucosal injury in IHD patients is essential for balancing cardiovascular protection and gastrointestinal safety.