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

Am Heart J. 2012 Oct;164(4):600-606.e1. doi: 10.1016/j.ahj.2012.06.008.

Abstract

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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Analysis of Variance
  • Arachidonic Acid / administration & dosage
  • Aspirin / administration & dosage*
  • Clopidogrel
  • Coronary Artery Disease / blood*
  • Coronary Artery Disease / complications
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetic Angiopathies / blood*
  • Drug Administration Schedule
  • Drug Resistance / physiology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Platelet Activation / drug effects
  • Platelet Activation / physiology
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Prospective Studies
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives

Substances

  • Platelet Aggregation Inhibitors
  • Arachidonic Acid
  • Clopidogrel
  • Ticlopidine
  • Aspirin