title: The influence of aspirin dose and glycemic control on platelet inhibition in patients with type 2 diabetes mellitus.
abstract: BACKGROUND
  Low-dose aspirin seems to offer no benefit in the primary prevention of cardiovascular disease in type 2 diabetes mellitus (DM2). The anti-platelet effect may be diminished by poor glycemic control or inadequate dosing of aspirin.
  
  
  OBJECTIVE
  To study the effects of both glycemic control and increasing aspirin dose on platelet response to aspirin in DM2 patients and matched controls.
  
  
  METHODS
  Platelet effects of increasing doses of aspirin (30, 100 and 300 mg daily) were prospectively assessed in 94 DM2 patients and 25 matched controls by measuring thromboxane levels in urine (11-dhTxB2) and platelet aggregation using VerifyNow(®) and light transmission aggregometry (LTA). DM2 patients were stratified for glycemic control (hemoglobin-A1c [HbA1c] ≤ 53, 53-69, ≥ 69 mmol mol(-1)).
  
  
  RESULTS
  At baseline, median 11-dhTxB2 excretion was higher in the poorly controlled patients (77 ng mmol(-1)), and the moderately controlled (84 ng mmol(-1)) compared with the well-controlled patients (64 ng mmol(-1)) and controls (53 ng mmol(-1)), P < 0.01. Next, 30 mg of aspirin reduced 11-dhTxB2 excretion to 31, 29 and 24 ng mmol(-1) in the poorly, moderately and well-controlled patients, respectively, and to 19 ng mmol(-1) in controls, P < 0.001. VerifyNow(®) and LTA were also incompletely suppressed in DM2 patients using 30 mg of aspirin, but 100 mg resulted in similar platelet suppression in all groups, with no additional effect of 300 mg.
  
  
  CONCLUSIONS
  DM2 patients with inadequate glycemic control (HbA1c > 53 mmol mol(-1)) have higher baseline platelet activity and incomplete suppression of platelet activity with 30 mg of aspirin. However, 100 mg of aspirin leads to optimal inhibition irrespective of glycemic control, and 300 mg does not further improve platelet suppression.
authors.affiliation: Department of Internal Medicine, Academic Medical Center, Amsterdam, the Netherlands. b.a.lemkes@amc.nl
authors.forename: B A
authors.initials: BA
authors.lastname: Lemkes
authors.forename: L
authors.initials: L
authors.lastname: Bähler
authors.forename: P W
authors.initials: PW
authors.lastname: Kamphuisen
authors.forename: A K
authors.initials: AK
authors.lastname: Stroobants
authors.forename: E J
authors.initials: EJ
authors.lastname: Van Den Dool
authors.forename: J B
authors.initials: JB
authors.lastname: Hoekstra
authors.forename: R
authors.initials: R
authors.lastname: Nieuwland
authors.forename: V E
authors.initials: VE
authors.lastname: Gerdes
authors.forename: F
authors.initials: F
authors.lastname: Holleman
mesh_terms: D000328:Adult; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage*; D015415:Biomarkers / Q000652:urine; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D016009:Chi-Square Distribution; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009426:Netherlands; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D010979:Platelet Function Tests; D011446:Prospective Studies; D012044:Regression Analysis; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine; D016896:Treatment Outcome
chemical_list: D001241:Aspirin; D015415:Biomarkers; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D010975:Platelet Aggregation Inhibitors; D013929:Thromboxane B2; C517652:hemoglobin A1c protein, human; C049235:11-dehydro-thromboxane B2