Assessing Pharmacokinetics and Pharmacodynamics of Daily Enteric-Coated Aspirin in Patients with Type 2 Diabetes: the Pilot APPEASED Study

Background Diabetes is a major cardiovascular risk factor. Although aspirin is recommended for secondary prevention, its role in primary prevention among patients with diabetes remains unclear. The APPEASED trial aimed to evaluate aspirin’s pharmacokinetics and pharmacodynamics in this population. Methods In this single-arm, open-label trial, 50 patients with type 2 diabetes and no evidence of atherosclerotic disease, received 81 mg of enteric-coated aspirin once daily for 7 days. Platelet function was assessed at baseline and on day 7 using light transmission aggregometry in response to arachidonic acid (primary endpoint) and measurement of circulating thromboxane B2 (TxB2) level (secondary endpoint). Oxidative stress markers, COX-1 acetylation, and COX-2 expression were also measured to explore mechanisms of on-treatment platelet reactivity. Results Ten participants (20%) exhibited high on-treatment platelet reactivity 24 hours after 6 days of aspirin. However, all showed complete platelet inhibition 2 hours after observed ingestion on day 7. Despite variability in platelet reactivity, COX-1 acetylation and TxB2 suppression were consistent across participants. No significant differences were found in oxidative stress markers or COX-2 expression. Conclusion In patients with type 2 diabetes in primary prevention, low-dose enteric-coated aspirin consistently achieved platelet inhibition shortly after ingestion, 20% of participants showed incomplete inhibition at 24 hours, despite adequate COX-1 acetylation and TxB2 suppression. These findings suggest that alternative aspirin regimens may be needed to ensure continuous platelet inhibition and optimize cardiovascular prevention in this high-risk population.