Abstract 15018: Better Platelet Inhibition in Whole Blood is Achieved by Twice Daily Dosing of Aspirin in Patients With Type 2 Diabetes Mellitus.
The efficacy of low dose aspirin in diabetes mellitus (DM) has been questioned. Diabetic patients have high platelet reactivity and may have a higher platelet turnover compared to non diabetics. We hypothesized that twice daily dosing of aspirin would be more effective than increasing the dose to 320 mg/day in type 2 DM.
Methods: A randomized, open, cross-over study in 25 patients with type 2 DM and micro- or macrovascular complications. Patients took 75mg aspirin once daily, 75mg twice daily or 320mg once daily for at least two weeks in a randomised order. Blood sampling was at the end of the dosing interval. Platelet responses to arachidonic acid (AA; 0.5 mM), collagen and ADP were examined by light transmittance aggregometry in platelet rich plasma (LTA), impedance aggregometry in whole blood (WBA; AA and collagen), the IMPACT-R Cone-and-Plate(let) Analyser in whole blood and urinary 11-dehydro-thromboxane B2 (TxM). Reticulated platelets (RP) and mean platelet volume (MPV) were measured as indices of platelet turnover.
Results: Aspirin 75mg BID decreased AA-induced WBA compared to 75 mg OD (9.7±4.5 vs 12.6±3.5 ohm; P=0.003) or to 320 mg OD (11.5±4.2 ohm; P= 0.005); 320 mg OD also gave better inhibition than 75 mg OD (P=0.049). WBA responses to collagen were similarly attenuated by 75 mg BID and 320 mg dosing (P= 0.02 for both). The IMPACT-R showed a better response to 75mg BID compared to 75 mg OD (mean surface coverage 4.1±2.2 vs 3.4±1.6% P=0.049), but not to 320 mg OD. All patients had low AA-induced aggregation using LTA with all aspirin dosages, indicating good compliance, and high aggregation with ADP and collagen, indicating highly reactive platelets. No differences between aspirin dosages were observed by LTA. Urinary TxM was reduced after 320 mg as compared to 75 mg OD (P=0.022) but not after 75 mg BID, probably reflecting better COX inhibition of other cells by the high dose. RP were well correlated with MPV (r2=0.74). In a stepwise regression analysis MPV correlated better than RP with AA-induced WBA during all treatment periods.
Conclusions: Our results support the hypothesis that twice daily dosing can improve the laboratory response to aspirin in type 2 DM. It may be worthwhile to study if twice daily dosing could improve the clinical efficacy of aspirin in DM.
- © 2010 by American Heart Association, Inc.