Biological efficacy of twice daily aspirin in type 2 diabetic patients with coronary artery disease

Background Diabetes is associated with a high rate of events after acute coronary syndrome and percutaneous coronary intervention despite aspirin treatment. Once daily aspirin might not provide 24-hour stable biological efficacy in patients with diabetes. We compared the biological efficacy of the same daily dose of aspirin given either once (OPD) or divided twice per day in a population of diabetic patients with previous coronary artery disease. Methods Ninety-two consecutive diabetic patients with at least 1 criteria of time-dependent aspirin efficacy, elevated high-sensibility C-reactive protein (hs-CRP), fibrinogen, platelet count, or active smoking were prospectively included. Consecutive patients were randomly treated with 150-mg aspirin daily given either OPD (150 mg in the morning) or twice per day (75 mg in the morning and 75 mg in the evening) in a crossover study. The main outcome was platelet reactivity to arachidonic acid (0.5 mg/mL) measured by light transmission aggregometry at trough level before morning aspirin intake. Results Mean maximum aggregation intensity triggered by arachidonic acid was 19.7% +/- 15.4% on OPD and 11.9% +/- 10.4% on twice per day (P < .0001). Biological resistance (maximum aggregation intensity >= 20%) was observed in 42% of patients on OPD and 17% on twice per day (P < .001). Of the 39 patients with biological resistance on OPD, 24 (62%) overcame resistance on twice per day. Of the 16 resistant on twice per day, only 1 patient (6%) overcame resistance on OPD. Results were concordant with global evaluation of platelet reactivity by Platelet Function Analyzer-100. A better twice per day efficacy was independent of clopidogrel cotreatment. Conclusion In a population of diabetic patients with coronary artery disease and a high risk of time-dependent aspirin resistance, aspirin divided twice per day can significantly decrease the rate of biological loss of efficacy at trough level. (Am Heart J 2012;164:600-606.e1.)