Pharmacodynamic Effects of Different Aspirin Dosing Regimens in Type 2 Diabetes Mellitus Patients With Coronary Artery Disease

Abstract

Background— Patients with type 2 diabetes mellitus (T2DM) have reduced aspirin-induced pharmacodynamic effects. This may be attributed to increased platelet turnover rates resulting in an increased proportion of non–aspirin-inhibited platelets during the daily dosing interval. The hypothesis of this study was that an increase in the frequency of drug administration [twice daily (bid) versus once daily (od)] may provide more effective platelet inhibition in T2DM patients. Methods and Results— T2DM patients with stable coronary artery disease were prospectively recruited. Patients modified their aspirin regimen on a weekly basis according to the following scheme: 81 mg/od, 81 mg/bid, 162 mg/od, 162 mg/bid, and 325 mg/od. Pharmacodynamic assessments included light-transmittance aggregometry after arachidonic acid, collagen and adenosine diphosphate stimuli; VerifyNow-Aspirin assay; and serum thromboxane B 2 (TXB 2 ) levels. Twenty patients were analyzed. All patients were sensitive and compliant to aspirin irrespective of dose, as assessed by arachidonic acid–induced aggregation. When aspirin was administered once daily, there was no significant effect on platelet reactivity by increasing the once-daily dosing using aspirin-sensitive assays (collagen-induced aggregation and VerifyNow-Aspirin). An increase in aspirin dose by means of a second daily administration was associated with a significant reduction in platelet reactivity assessed by collagen-induced aggregation and VerifyNow-Aspirin between 81 mg/od and 81 mg/bid ( P <0.05 for both assays) and between 81 mg/od and 162 mg/bid ( P <0.05 for both assays). There was no impact of aspirin dosing regimens on adenosine diphosphate–induced aggregation. A dose-dependent effect of aspirin was observed on serum TXB 2 levels ( P =0.003). Conclusions— Aspirin dosing regimens are associated with different pharmacodynamic effects in platelets from T2DM patients and stable coronary artery disease, with a twice-daily, low-dose aspirin administration resulting in greater platelet inhibition than once-daily administration as assessed by aspirin-sensitive assays and a dose-dependent effect on serum TXB 2 levels. The clinical implications of a modified aspirin regimen tailored to T2DM patients warrant further investigation. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01201785.