GW24-e3986 Aspirin given twice daily reduced the platelet reactivity more than once daily in people with type 2 diabetes without cardiovascular disease

Abstract

Objectives In type 2 diabetes (T2DM), low dose Aspirin has been established for secondary cardiovascular prevention, but as yet there is no definitive data showing primary cardiovascular prevention. We hypothesized that a double dose of ASA would further reduce platelet reactivity and, given the increased platelet turnover, may be most effective when given in divided doses twice-daily. Methods This 3-period, 3-treatment, crossover study randomized 24 adults (51 ± 7 years old, BMI 31.4 ± 7.2 kg/m2, HbA1c 47 ± 7 mmol/mol) with T2DM and no prior cardiovascular disease to 2-week treatment periods with single (100 mg once-daily), double (200 mg once-daily) or split (100 mg twice-daily) ASA doses, with intervening 2 week washout periods. A generalized linear mixed model with random subject effect was used to estimate the dose response of platelet reactivity using Verify Now ASA™ as the primary outcome. Results ASA at all doses significantly reduced platelet reactivity measured by all platelet function tests except PFA-100 CADP. Verify Now ASA™ was decreased significantly from baseline 650.0 ± 19.4 aspirin reaction units (ARU) to 447.6 ± 68.1 ARU with single dose (p<0.0001), 430.1 ± 64.6 ARU with double dose (p<0.0001), and 416.4 ± 38.5 ARU with split dose (p<0.0001) aspirin. After fitting the model, Verify Now ASA™ was reduced to a greater extent with split dose compared with single dose ASA (p = 0.043), but did not differ significantly for single versus double dose (p = 0.20) or double versus split dose (p = 0.44). Split dose was also more effective compared to single dose, as measured by PFA-100™ CEPI (p = 0.031) and urinary thromboxane (p = 0.048) with a trend toward reduced reactivity measured by serum thromboxane (p = 0.055). Both high (p = 0.0043) and split (p<0.0001) doses were more effective than low dose ASA at reducing AA-induced Multiplate™ aggregation. No significant differences between ASA doses were seen for LTA (AA and ADP) or PFA-100™ CADP. Conclusions ASA 100 mg given twice-daily was numerically the most effective regimen for reducing platelet reactivity as measured by platelet function tests, but future clinical outcome trials are required to confirm whether ASA 100 mg twice-daily will reduce the risk of primary cardiovascular events in patients with T2DM. Clinical Trial Registration: 2011-003123-35 (need to list URL for EUDRACT website)