Long-Term Effects of Low-Dose Aspirin on Gastrointestinal Symptoms and Bleeding Complications in Patients with Type 2 Diabetes

Am J Cardiovasc Drugs. 2024 Sep 28. doi: 10.1007/s40256-024-00679-9. Online ahead of print.

Abstract

Background: Low-dose aspirin for primary prevention is determined by the balance of risks of cardiovascular events and adverse effects. We assessed the long-term gastrointestinal symptoms or bleeding with low-dose aspirin in diabetic patients.

Methods: The Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial was a randomized clinical trial to evaluate the efficacy and safety of low-dose aspirin in patients with type 2 diabetes. As a post hoc analysis, we investigated the incidence of upper gastrointestinal symptoms or bleeding in aspirin (100 mg enteric-coated aspirin or 81 mg buffered aspirin daily) and no-aspirin groups within and beyond 3 years.

Results: Of 2535 patients (mean age 65 years, 55% male) followed for a median of 11.2 years, 1258 were included in the aspirin group (951 enteric-coated, 208 buffered, 99 unknown) and 1277 were included in the no-aspirin group. The cumulative incidence of upper gastrointestinal symptoms or bleeding was higher in the aspirin group than the no-aspirin group (8.8% vs. 5.7% at 18 years; p < 0.0001). The increased risk in the aspirin group was prominent within 3 years, and the hazard ratio (HR) [95% confidence interval (CI)] of the aspirin group was 7.10 [3.21-15.7], but attenuated beyond 3 years (HR 1.20 [0.76-1.89]). In 1159 patients in the aspirin group, the cumulative incidence was lower in the enteric-coated than in the buffered aspirin groups (2.9% vs. 7.3%; p = 0.003) within 3 years, and the adjusted HR of enteric-coated aspirin was 0.38 [0.20-0.72] compared with the buffered aspirin group.

Conclusion: The upper gastrointestinal symptoms or bleeding of low-dose aspirin within 3 years, and the aspirin formulations, were relevant for decision making of initiation and continuation of low-dose aspirin for primary prevention.