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.


CONCLUSIONS
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.
Cardiology-Lariboisiere Hospital, AP-HP-Paris Diderot University, INSERM U942, Paris, France.
Jean-Guillaume
JG
Dillinger
Akram
A
Drissa
Georgios
G
Sideris
Claire
C
Bal dit Sollier
Sebastian
S
Voicu
Stephane
S
Manzo Silberman
Damien
D
Logeart
Ludovic
L
Drouet
Patrick
P
Henry
D000704:Analysis of Variance; D016718:Arachidonic Acid / Q000008:administration & dosage; D001241:Aspirin / Q000008:administration & dosage*; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood* / Q000150:complications; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications; D003925:Diabetic Angiopathies / Q000097:blood*; D004334:Drug Administration Schedule; D004351:Drug Resistance / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D011446:Prospective Studies; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives
D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin