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

Platelets (2014-04-23)
Kristian H Christensen, Erik L Grove, Morten Würtz, Steen D Kristensen, Anne-Mette Hvas
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Aspirin, meets USP testing specifications
Sigma-Aldrich
Arachidonic acid, from non-animal source, ≥98.5% (GC)
Supelco
Aspirin (Acetyl Salicylic Acid), Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Arachidonic acid, >95.0% (GC)
USP
Aspirin, United States Pharmacopeia (USP) Reference Standard
Acetylsalicylic acid for peak identification, European Pharmacopoeia (EP) Reference Standard
Acetylsalicylic acid, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Acetylsalicylic acid, ≥99.0%
Sigma-Aldrich
Acetylsalicylic acid, analytical standard