A randomised controlled trial to assess the antithrombotic effects of aspirin in type 1 diabetes: role of dosing and glycaemic control

Abstract

Background The enhanced thrombotic milieu in diabetes contributes to increased risk of vascular events. Aspirin, a key antiplatelet agent, has inconsistent effects on outcomes in diabetes and the best dosing regimen remains unclear. This work investigated effects of aspirin dose and interaction with glycaemia on both the cellular and protein components of thrombosis. Methods A total of 48 participants with type 1 diabetes and 48 healthy controls were randomised to receive aspirin 75 or 300 mg once-daily (OD) in an open-label crossover study. Light transmittance aggregometry and fibrin clot studies were performed before and at the end of each treatment period. Results Aspirin demonstrated reduced inhibition of collagen-induced platelet aggregation (PA) in participants with diabetes compared with controls, although the higher dose showed better efficacy. Higher aspirin dose facilitated clot lysis in controls but not individuals with diabetes. Collagen-induced PA correlated with glycaemic control, those in the top HbA1c tertile having a lesser inhibitory effect of aspirin. Threshold analysis suggested HbA1c levels of > 65 mmol/mol and > 70 mmol/mol were associated with poor aspirin response to 75 and 300 mg daily doses, respectively. Higher HbA1c was also associated with longer fibrin clot lysis time. Conclusions Patients with diabetes respond differently to the antiplatelet and profibrinolytic effects of aspirin compared with controls. In particular, those with elevated HbA1c have reduced inhibition of PA with aspirin. Our findings indicate that reducing glucose levels improves the anti-thrombotic action of aspirin in diabetes, which may have future clinical implications. Trial registration EudraCT, 2008-007875-26, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2008-007875-26.

Evaluating thrombosis risk and patient-specific treatment strategy using an atherothrombosis-on-chip model

“…79 A randomised control trial suggested that participants with diabetes demonstrated reduced inhibition of collagen-induced platelet aggregation with a low dose of aspirin (75 mg once daily), while a higher dose proved effective (300 mg once daily). 80 A recent study involving 15 076 patients with established cardiovascular disease using low (82 mg twice daily) or high (325 mg twice daily) doses of aspirin found no significant differences in mortality, hospitalisation for myocardial infarction, stroke rates, or hazard ratio. 81 Another study suggested that low doses of aspirin fail to prevent vascular prostacyclin formation, whereas high doses suppress COX-2 production and inhibit inflammation.…”

The Cellular and Protein Arms of Coagulation in Diabetes: Established and Potential Targets for the Reduction of Thrombotic Risk

“…Moreover, it remains unclear whether the use of a P2Y 12 inhibitor monotherapy for long-term prevention is superior to aspirin as some biochemical data suggest this may well be the case [116]. Also, the interaction between glycaemia and the response to antiplatelet therapies requires further research [117], in order to optimise antithrombotic management in diabetes. In short, there is still a significant amount of work to do with existing antiplatelet agents to optimise their use, before moving to new antiplatelet targets outside the thromboxane and P2Y 12 pathways.…”