Parker, W.A.E. orcid.org/0000-0002-7822-8852, Sagar, R., Kurdee, Z. et al. (5 more authors) (2021) A randomised controlled trial to assess the antithrombotic effects of aspirin in type 1 diabetes : role of dosing and glycaemic control. Cardiovascular Diabetology, 20 (1). 238.
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
Keywords: | Aspirin; Diabetes mellitus; Fibrin; Platelet inhibition |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 11 Jan 2022 07:52 |
Last Modified: | 11 Jan 2022 07:52 |
Published Version: | https://cardiab.biomedcentral.com/articles/10.1186... |
Status: | Published |
Publisher: | BioMed Central |
Refereed: | Yes |
Identification Number: | 10.1186/s12933-021-01427-y |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:182266 |