Reduced antiplatelet effect of aspirin during 24 hours in patients with coronary artery disease and type 2 diabetes

Abstract

Reduced antiplatelet effect of aspirin has been reported in patients with type 2 diabetes, and recent studies suggest that once-daily aspirin provides insufficient platelet inhibition. We investigated if the effect of aspirin declined during the 24-hour dosing interval in patients with coronary artery disease and type 2 diabetes, and whether this correlated with increased platelet turnover. Furthermore, the intra-individual variation in platelet aggregation was determined during a 28-day period. We included 47 patients with coronary artery disease and type 2 diabetes treated with aspirin 75 mg daily. Blood samples were obtained 1 and 24 hours after aspirin intake, and this was repeated three times with a 2-week interval between each visit. Platelet aggregation was evaluated by impedance aggregometry (Multiplate® Analyzer) using arachidonic acid (1.0 mM) and collagen (3.2 µg/ml) as agonists. Markers of platelet turnover were measured by flow cytometry. Compliance was confirmed by serum thromboxane B₂. Platelet aggregation levels measured 1 and 24 hours after aspirin intake were compared using the mean of 1- and 24-hour measurements at the three study visits. The difference in platelet aggregation was 70 ± 97 AU × min (p < 0.0001) when using arachidonic acid as agonist and 33 ± 76 AU × min (p = 0.01) when using collagen. Markers of platelet turnover correlated positively, though not significantly, with residual platelet aggregation 24 hours after aspirin intake (p values 0.06 and 0.07). Median intra-individual variation of platelet aggregation was 9–16%. Patients with coronary artery disease and type 2 diabetes had increased platelet aggregation at the end of the 24-hour aspirin dosing interval. Platelet turnover did not correlate significantly with residual platelet aggregation, although a trend was observed. The intra-individual variation of platelet aggregation after aspirin intake was low.

• Aspirin
• coronary artery disease
• diabetes mellitus
• platelet aggregation
• platelet function tests
• platelet turnover

Acknowledgements

We gratefully acknowledge the help from laboratory technicians Vivi Bo Mogensen and Mai Stenulm Therkelsen who provided laboratory assistance and performed all ELISA analyses.

Declaration of interest

E.L.G. has received speaker honoraria from AstraZeneca, Baxter, Bayer, Boehringer Ingelheim, Pfizer and Sysmex and serves on advisory boards for AstraZeneca, Bayer, and Bristol-Myers Squibb. S.D.K. has received speaker honoraria form AstraZeneca, Eli Lilly, Sanofi and The Medicines Company. K.H.C., A.M.H. and M.W. have no conflicts of interest to declare. The study was financially supported by The Central Denmark Region and the Institute of Clinical Medicine at Aarhus University, Arvid Nilssons Fond, Snedkermester Sophus Jacobsen og Hustru Astrid Jacobsens Fond, and Direktør Jacob Madsen og Hustru Olga Madsens Fond.