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. Patients/Methods. One hundred type 2 diabetic and 73 non-diabetic patients on chronic aspirin 100mg daily were studied. Serum TXB2 was measured every 3h, between 12 and 24h after a witnessed aspirin intake, to characterize the kinetics of platelet cyclooxygenase-1 recovery. Patients with the fastest TXB2 recovery were randomized to aspirin 100mg once daily, 200mg once daily or 100mg twice daily, for 28days and TXB2 recovery was reassessed. Results and Conclusions. Platelet TXB2 production was profoundly suppressed at 12h in both groups. Serum TXB2 recovered linearly, with a large interindividual variability in slope. Diabetic patients in the third tertile of recovery slopes (≥0.10ngmL-1h-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 100mg twice daily completely reversed the abnormal TXB2 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. © 2012 International Society on Thrombosis and Haemostasis.