title: Randomized controlled trial comparing impact on platelet reactivity of twice-daily with once-daily aspirin in people with Type 2 diabetes.
abstract: OBJECTIVE
  Reduced aspirin efficacy has been demonstrated in people with Type 2 diabetes. Because increased platelet reactivity and/or turnover are postulated mechanisms, we examined whether higher and/or more frequent aspirin dosing might reduce platelet reactivity more effectively.
  
  
  METHODS
  Participants with Type 2 diabetes (n = 24) but without known cardiovascular disease were randomized in a three-way crossover design to 2-week treatment periods with aspirin 100 mg once daily, 200 mg once daily or 100 mg twice daily. The primary outcome was platelet reactivity, assessed using the VerifyNow(™) ASA method. Relationships between platelet reactivity and aspirin dosing were examined using generalized linear mixed models with random subject effects.
  
  
  RESULTS
  Platelet reactivity decreased from baseline with all doses of aspirin. Modelled platelet reactivity was more effectively reduced with aspirin 100 mg twice daily vs. 100 mg once daily, but not vs. 200 mg once daily. Aspirin 200 mg once daily did not differ from 100 mg once daily. Aspirin 100 mg twice daily was also more effective than once daily as measured by collagen/epinephrine-stimulated platelet aggregation and urinary thromboxane levels, with a similar trend measured by serum thromboxane levels. No episodes of bleeding occurred.
  
  
  CONCLUSIONS
  In Type 2 diabetes, aspirin 100 mg twice daily reduced platelet reactivity more effectively than 100 mg once daily, and numerically more than 200 mg once daily. Clinical outcome trials evaluating primary cardiovascular disease prevention with aspirin in Type 2 diabetes may need to consider using a more frequent dosing schedule.
authors.affiliation: Diabetes Trials Unit, University of Oxford, Oxford, UK.|Oxford National Institute for Health Research Biomedical Research Centre, Churchill Hospital, Oxford, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Bethel
authors.affiliation: School of Immunity and Infection, University of Birmingham Medical School, Birmingham, UK.
authors.forename: P
authors.initials: P
authors.lastname: Harrison
authors.affiliation: Diabetes Trials Unit, University of Oxford, Oxford, UK.|Oxford National Institute for Health Research Biomedical Research Centre, Churchill Hospital, Oxford, UK.
authors.forename: H
authors.initials: H
authors.lastname: Sourij
authors.affiliation: Peking University People's Hospital, Beijing, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Diabetes Trials Unit, University of Oxford, Oxford, UK.|Oxford National Institute for Health Research Biomedical Research Centre, Churchill Hospital, Oxford, UK.
authors.forename: L
authors.initials: L
authors.lastname: Tucker
authors.affiliation: Diabetes Trials Unit, University of Oxford, Oxford, UK.|Oxford National Institute for Health Research Biomedical Research Centre, Churchill Hospital, Oxford, UK.
authors.forename: I
authors.initials: I
authors.lastname: Kennedy
authors.affiliation: Diabetes Trials Unit, University of Oxford, Oxford, UK.|Oxford National Institute for Health Research Biomedical Research Centre, Churchill Hospital, Oxford, UK.
authors.forename: S
authors.initials: S
authors.lastname: White
authors.affiliation: Department of Haematology, John Radcliffe Hospital, Oxford, UK.
authors.forename: L
authors.initials: L
authors.lastname: Hill
authors.affiliation: Diabetes Trials Unit, University of Oxford, Oxford, UK.|Oxford National Institute for Health Research Biomedical Research Centre, Churchill Hospital, Oxford, UK.
authors.forename: A
authors.initials: A
authors.lastname: Oulhaj
authors.affiliation: Diabetes Trials Unit, University of Oxford, Oxford, UK.
authors.forename: R L
authors.initials: RL
authors.lastname: Coleman
authors.affiliation: Diabetes Trials Unit, University of Oxford, Oxford, UK.|Oxford National Institute for Health Research Biomedical Research Centre, Churchill Hospital, Oxford, UK.
authors.forename: R R
authors.initials: RR
authors.lastname: Holman
mesh_terms: D000328:Adult; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000150:complications / Q000453:epidemiology / Q000517:prevention & control*; D018592:Cross-Over Studies; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications*; D003925:Diabetic Angiopathies / Q000453:epidemiology / Q000517:prevention & control*; D058065:Diabetic Cardiomyopathies / Q000453:epidemiology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004351:Drug Resistance; D004739:England / Q000453:epidemiology; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced / Q000150:complications / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D012306:Risk; D018570:Risk Assessment
chemical_list: D016861:Cyclooxygenase Inhibitors; D010975:Platelet Aggregation Inhibitors; D001241:Aspirin