Abstract 14822: Aspirin Given Twice Daily Reduced the Platelet Reactivity More Than Once Daily in People With Type 2 Diabetes Without Cardiovascular Disease
Background: In type 2 diabetes (T2DM), Aspirin at low doses 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 and Results: 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 VerifyNow ASA™ as the primary outcome.
ASA at all doses significantly reduced platelet reactivity measured by all platelet function tests except PFA-100 CADP. VerifyNow 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, VerifyNow 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.
- © 2013 by American Heart Association, Inc.