Twice daily dosing of aspirin improves platelet inhibition in whole blood in patients with type 2 diabetes mellitus and micro- or macrovascular complications

Abstract

The efficacy of low-dose aspirin in type 2 diabetes mellitus (T2DM) has been questioned. We tested if twice daily dosing of aspirin would be more effective in T2DM, possibly due to increased platelet turnover. A randomised cross-over study compared 75 mg aspirin OD, 75 mg BID and 320 mg OD (≥ 2 week treatment periods) in 25 patients with T2DM and micro- or macrovascular complications. Platelet responses were examined by impedance aggregometry (WBA) and the IMPACT-R aspirin test in whole blood, light transmittance aggregometry in platelet-rich plasma (LTA), and urinary 11-dehydro-thromboxane B2 (TxM). Aspirin 75 mg BID decreased arachidonic acid (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 Ohms; p = 0.049). WBA responses to collagen were similarly attenuated by BID or high dosing (by 12-14%; p = 0.02 for both). The IMPACT-R showed a better response to 75 mg BID compared to 75 mg OD (p = 0.049), but not to 320 mg OD. AA-induced aggregation by LTA was <6.5% on all occasions, with no differences between aspirin dosages. TxM was reduced after 320 mg OD (p = 0.002), but not 75 mg BID (p = 0.07). Reticulated platelets were highly correlated with mean platelet volume (MPV; r2 = 0.74, p<0.0001). Both markers for platelet turnover were correlated with AA-induced WBA, but neither identified patients who benefited from BID dosing dependably. In conclusion, twice daily dosing improved laboratory responses to aspirin in high risk T2DM patients. Studies of whether BID dosing of aspirin can improve clinical outcomes in such patients are of interest.

In Vivo Platelet Activation and Aspirin Responsiveness in Type 1 Diabetes

“…Consistently, we found no evidence of accelerated platelet turnover in T1DM as shown by a number of reticulated platelets that were even slightly decreased in patients (Supplementary Table 2). These findings demonstrate, for the first time, that T1DM does not share the abnormal aspirin pharmacodynamics previously described in T2DM (9,10). Neither glycemic control nor its 24-h variability influenced aspirin responsiveness of T1DM, providing indirect evidence that the impaired platelet COX-1 inhibition reported in T2DM is not a consequence of hyperglycemia.…”

“…However, the duration of the antiplatelet effect of low-dose aspirin may be reduced in patients with T2DM, and a twice-daily dosing improves inhibition of T2DM platelets versus the standard oncedaily regimen (9,10). Whether this applies to T1DM remains unexplored.…”

Antithrombotic Therapy for Secondary Prevention in Patients With Diabetes Mellitus and Coronary Artery Disease

“…21 Several studies have demonstrated that twice-daily administration of aspirin resulted in greater platelet inhibition than once-daily administration and a dosedependent suppression of serum TXB2 levels in DM patients. [17][18][19] However, the clinical implications of a twice-daily dosing regimen remain unknown. Figure 3).…”

The prognostic utility of tests of platelet function for the detection of ‘aspirin resistance’ in patients with established cardiovascular or cerebrovascular disease: a systematic review and economic evaluation

“…[66][67][68][69][70] Increasing the frequency of aspirin administration to twice daily has been shown to effectively improve the inhibition of platelet function by aspirin in these settings, although the clinical benefit of this therapy modification remains unknown. 63,64,[71][72][73] Although the characteristics associated with poor response have been explored in detail, 74 it is noteworthy that the different studies have used different platelet function methodologies to explore the determinants of platelet responses. In parallel, a number of different studies have shown platelet function assay results to lack correlation and agreement among themselves, thus identifying different patients as poor responders to aspirin and having different determinants of response.…”