title: The recovery of platelet cyclooxygenase activity explains interindividual variability in responsiveness to low-dose aspirin in patients with and without diabetes.
abstract: BACKGROUND
  Interindividual variability in response to aspirin has been popularized as 'resistance'. We hypothesized that faster recovery of platelet cyclooxygenase-1 activity may explain incomplete thromboxane (TX) inhibition during the 24-h dosing interval.
  
  
  OBJECTIVE
  To characterize the kinetics and determinants of platelet cyclooxygenase-1 recovery in aspirin-treated diabetic and non-diabetic patients.
  
  
  METHODS
  One hundred type 2 diabetic and 73 non-diabetic patients on chronic aspirin 100 mg daily were studied. Serum TXB(2) was measured every 3 h, between 12 and 24 h after a witnessed aspirin intake, to characterize the kinetics of platelet cyclooxygenase-1 recovery. Patients with the fastest TXB(2) recovery were randomized to aspirin 100 mg once daily, 200 mg once daily or 100 mg twice daily, for 28 days and TXB(2) recovery was reassessed.
  
  
  CONCLUSIONS
  Platelet TXB(2) production was profoundly suppressed at 12 h in both groups. Serum TXB(2) recovered linearly, with a large interindividual variability in slope. Diabetic patients in the third tertile of recovery slopes (≥ 0.10 ng mL(-1) h(-1) ) showed significantly higher mean platelet volume and body mass index, and younger age. Higher body weight was the only independent predictor of a faster recovery in non-diabetics. Aspirin 100 mg twice daily completely reversed the abnormal TXB(2) recovery in both groups. Interindividual variability in the recovery of platelet cyclooxygenase activity during the dosing interval may limit the duration of the antiplatelet effect of low-dose aspirin in patients with and without diabetes. Inadequate thromboxane inhibition can be easily measured and corrected by a twice daily regimen.
authors.affiliation: Department of Pharmacology, Catholic University School of Medicine, Rome, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Rocca
authors.forename: F
authors.initials: F
authors.lastname: Santilli
authors.forename: D
authors.initials: D
authors.lastname: Pitocco
authors.forename: L
authors.initials: L
authors.lastname: Mucci
authors.forename: G
authors.initials: G
authors.lastname: Petrucci
authors.forename: E
authors.initials: E
authors.lastname: Vitacolonna
authors.forename: S
authors.initials: S
authors.lastname: Lattanzio
authors.forename: D
authors.initials: D
authors.lastname: Mattoscio
authors.forename: F
authors.initials: F
authors.lastname: Zaccardi
authors.forename: R
authors.initials: R
authors.lastname: Liani
authors.forename: N
authors.initials: N
authors.lastname: Vazzana
authors.forename: A
authors.initials: A
authors.lastname: Del Ponte
authors.forename: E
authors.initials: E
authors.lastname: Ferrante
authors.forename: F
authors.initials: F
authors.lastname: Martini
authors.forename: C
authors.initials: C
authors.lastname: Cardillo
authors.forename: R
authors.initials: R
authors.lastname: Morosetti
authors.forename: M
authors.initials: M
authors.lastname: Mirabella
authors.forename: G
authors.initials: G
authors.lastname: Ghirlanda
authors.forename: G
authors.initials: G
authors.lastname: Davì
authors.forename: C
authors.initials: C
authors.lastname: Patrono
mesh_terms: D000368:Aged; D001241:Aspirin / Q000008:administration & dosage*; D001792:Blood Platelets / Q000201:enzymology*; D016022:Case-Control Studies; D051545:Cyclooxygenase 1 / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D013929:Thromboxane B2 / Q000097:blood
chemical_list: D013929:Thromboxane B2; D051545:Cyclooxygenase 1; D001241:Aspirin