The platelet-inhibitory effect of low-dose acetylsalicylic acid is dependent on glycaemic control in type 2 diabetes

Background and aims: The clinical benefit of low-dose acetylsalicylic acid (ASA) treatment in primary prevention of cardiovascular events in type 2 diabetes (DM2) remains controversial. The platelet response to ASA has been suggested to be diminished in diabetes, but the role of hyperglycaemia has not yet been elucidated. In this study we determined whether (i) the baseline platelet activity and response to ASA differs in patients with DM2 as compared to healthy controls, (ii) glycaemic control influences the platelet response to ASA in DM2 and (iii) higher doses of ASA improve the platelet response in DM2. Materials and methods: This is a prospective, single-centre, open-label trial. We aim to include 125 subjects and report here the preliminary data for 102 subjects. DM2 patients are categorized by HbA1c value <7.0% (DC1: n=34), 7.0- 8.5% (DC2: n=33) and > 8.5% (DC3: n=22) and compared to healthy controls (HC: n=13). All subjects underwent three treatment periods, sequentially using 30 mg, 100 mg and 300 mg of ASA for ten days. Laboratory measurements were performed at baseline and following each treatment period. To assess the pharmacological efficacy of ASA, urinary 11-dehydrothromboxane B2 (11dhTxB2) was measured by ELISA. Platelet function was measured by optical platelet aggregation and Verify Now. Results: Median baseline urinary 11dhTxB2 excretion was 45 pg/mmol (IQR 36-59) in HC, compared to 69 in DC1 (IQR 37-93), 84 in DC2 (IQR 47- 101) and 95 in DC3 (IQR 73-143) (p=0.007, ANOVA). Treatment with ASA 30 mg significantly reduced 11dhTxB2 by 62%, 67%, 64% and 68% respectively. Absolute excretion remained significantly different between groups, and followed the same pattern as baseline (p=0.001). Subsequent treatment with 100 mg ASA further reduced 11dhTxB2 in DC2 (p