PB0035 - Assessing Pharmacokinetics and Pharmacodynamics of daily Enteric-coated Aspirin in patients with StablE Diabetes: preliminary findings from the APPEASED study

Background: Aspirin is widely used for the prevention of major adverse cardiovascular events. Recent studies have shown that the net benefit is uncertain in diabetic patients with no history of cardiovascular disease. However, these studies used an enteric-coated formulation of aspirin given once daily, which could potentially not be suitable for sustained inhibition of platelets in diabetic patients.

Aims: To assess the proportion of patients with diabetes who express unsustained platelet inhibition by once daily enteric-coated aspirin.

Methods: The study received ethical approval and all participants gave informed consent. Patients were eligible if they had diabetes, but no established atherosclerotic cardiovascular disease. Participants provided blood samples before and after 6 days of daily enteric-coated aspirin (24h post last dose), and 2h after the 7th daily dose was administered on site. Platelet aggregation was measured by light transmission aggregometry in response to arachidonic acid (primary outcome) and other classical agonists (secondary outcomes). Insufficient platelet inhibition was defined as >20% residual aggregation to arachidonic acid.

Results: Of the 28 participants included in the study, 4 (14%) demonstrated insufficient inhibition of platelet function in response to arachidonic acid at 24 hours after 6 days of daily aspirin intake. However, 2 hours after the observed intake of aspirin, adequate inhibition of platelet function was seen in all participants.

Conclusion(s): Preliminary results reveal that 14% of patients studied do not respond to aspirin 24 hours after the last dose, and 0% at 2 hours after witnessed intake. Despite previous reports suggesting enteric coating blunts the response to aspirin in patients with diabetes, witnessed intake of aspirin showed no major pharmacokinetic variation 2 hours post-dosing. This suggests pharmacodynamic rather than pharmacokinetic causes of aspirin resistance, and support a trial of twice-daily dosing in patients with diabetes.