M A Bethel1,2, P Harrison3, H Sourij1,2, Y Sun4, L Tucker1,2, I Kennedy1,2, S White1,2, L Hill5, A Oulhaj1,2, R L Coleman1, R R Holman1,2. 1. Diabetes Trials Unit, University of Oxford, Oxford, UK. 2. Oxford National Institute for Health Research Biomedical Research Centre, Churchill Hospital, Oxford, UK. 3. School of Immunity and Infection, University of Birmingham Medical School, Birmingham, UK. 4. Peking University People's Hospital, Beijing, People's Republic of China. 5. Department of Haematology, John Radcliffe Hospital, Oxford, UK.
Abstract
AIMS: Reduced aspirin efficacy has been demonstrated in people with Type 2 diabetes. Because increased platelet reactivity and/or turnover are postulated mechanisms, we examined whether higher and/or more frequent aspirin dosing might reduce platelet reactivity more effectively. METHODS:Participants with Type 2 diabetes (n = 24) but without known cardiovascular disease were randomized in a three-way crossover design to 2-week treatment periods with aspirin 100 mg once daily, 200 mg once daily or 100 mg twice daily. The primary outcome was platelet reactivity, assessed using the VerifyNow(™) ASA method. Relationships between platelet reactivity and aspirin dosing were examined using generalized linear mixed models with random subject effects. RESULTS:Platelet reactivity decreased from baseline with all doses of aspirin. Modelled platelet reactivity was more effectively reduced with aspirin 100 mg twice daily vs. 100 mg once daily, but not vs. 200 mg once daily. Aspirin 200 mg once daily did not differ from 100 mg once daily. Aspirin 100 mg twice daily was also more effective than once daily as measured by collagen/epinephrine-stimulated platelet aggregation and urinary thromboxane levels, with a similar trend measured by serum thromboxane levels. No episodes of bleeding occurred. CONCLUSIONS: In Type 2 diabetes, aspirin 100 mg twice daily reduced platelet reactivity more effectively than 100 mg once daily, and numerically more than 200 mg once daily. Clinical outcome trials evaluating primary cardiovascular disease prevention with aspirin in Type 2 diabetes may need to consider using a more frequent dosing schedule.
RCT Entities:
AIMS: Reduced aspirin efficacy has been demonstrated in people with Type 2 diabetes. Because increased platelet reactivity and/or turnover are postulated mechanisms, we examined whether higher and/or more frequent aspirin dosing might reduce platelet reactivity more effectively. METHODS:Participants with Type 2 diabetes (n = 24) but without known cardiovascular disease were randomized in a three-way crossover design to 2-week treatment periods with aspirin 100 mg once daily, 200 mg once daily or 100 mg twice daily. The primary outcome was platelet reactivity, assessed using the VerifyNow(™) ASA method. Relationships between platelet reactivity and aspirin dosing were examined using generalized linear mixed models with random subject effects. RESULTS: Platelet reactivity decreased from baseline with all doses of aspirin. Modelled platelet reactivity was more effectively reduced with aspirin 100 mg twice daily vs. 100 mg once daily, but not vs. 200 mg once daily. Aspirin 200 mg once daily did not differ from 100 mg once daily. Aspirin 100 mg twice daily was also more effective than once daily as measured by collagen/epinephrine-stimulated platelet aggregation and urinary thromboxane levels, with a similar trend measured by serum thromboxane levels. No episodes of bleeding occurred. CONCLUSIONS: In Type 2 diabetes, aspirin 100 mg twice daily reduced platelet reactivity more effectively than 100 mg once daily, and numerically more than 200 mg once daily. Clinical outcome trials evaluating primary cardiovascular disease prevention with aspirin in Type 2 diabetes may need to consider using a more frequent dosing schedule.
Authors: Felix Aberer; Peter N Pferschy; Norbert J Tripolt; Caren Sourij; Anna M Obermayer; Florian Prüller; Eva Novak; Philipp Reitbauer; Harald Kojzar; Barbara Prietl; Selina Kofler; Martina Brunner; Eva Svehlikova; Tatjana Stojakovic; Hubert Scharnagl; Abderrahim Oulhaj; Faisal Aziz; Regina Riedl; Harald Sourij Journal: Diabetes Obes Metab Date: 2019-11-03 Impact factor: 6.577