Abstract
BackgroundDespite increased atherothrombotic risk in type 2 diabetes mellitus, (T2DM) the best preventative antithrombotic strategy remains undetermined. We defined the effects of three antiplatelet agents on functional readout and biomarker kinetics in platelet activation and coagulation in patients with T2DM.Materials and methods56 patients with T2DM were randomised to antiplatelet monotherapy with aspirin 75 mg once daily (OD), clopidogrel 75 mg OD or prasugrel 10 mg OD during three periods of a crossover study. Platelet aggregation (PA) was determined by light-transmittance aggregometry and P-selectin expression by flow cytometry. Markers of fibrin clot dynamics, inflammation and coagulation were measured. Plasma levels of 14 miRNA were assessed by quantitative polymerase chain reactions.ResultsOf the 56 patients, 24 (43%) were receiving aspirin for primary prevention of ischaemic events and 32 (57%) for secondary prevention. Prasugrel was the strongest inhibitor of ADP-induced PA (mean ± SD maximum response to 20μmol/L ADP 77.6 ± 8.4% [aspirin] vs. 57.7 ± 17.6% [clopidogrel] vs. 34.1 ± 14.1% [prasugrel], p < 0.001), P-selectin expression (30 μmol/L ADP; 45.1 ± 21.4% vs. 27.1 ± 19.0% vs. 14.1 ± 14.9%, p < 0.001) and collagen-induced PA (2 μg/mL; 62.1 ± 19.4% vs. 72.3 ± 18.2% vs. 60.2 ± 18.5%, p < 0.001). Fibrin clot dynamics and levels of coagulation and inflammatory proteins were similar. Lower levels of miR-24 (p = 0.004), miR-191 (p = 0.019), miR-197 (p = 0.009) and miR-223 (p = 0.014) were demonstrated during prasugrel-therapy vs. aspirin. Circulating miR-197 was lower in those cardiovascular disease during therapy with aspirin (p = 0.039) or prasugrel (p = 0.0083).ConclusionsPrasugrel monotherapy in T2DM provided potent platelet inhibition and reduced levels of a number of platelet-associated miRNAs. miR-197 is a potential marker of cardiovascular disease in this population. Clinical outcome studies investigating prasugrel monotherapy are warranted in individuals with T2DM.Trial registration EudraCT, 2009-011907-22. Registered 15 March 2010, https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-011907-22/GB.
Highlights
Despite increased atherothrombotic risk in type 2 diabetes mellitus, (T2DM) the best preventative antithrombotic strategy remains undetermined
Prasugrel was the strongest inhibitor of adenosine diphosphate- (ADP-)induced Platelet aggregation (PA), P-selectin expression (30 μmol/L ADP; 45.1 ± 21.4% vs. 27.1 ± 19.0% vs. 14.1 ± 14.9%, p < 0.001) and collagen-induced PA (2 μg/ mL; 62.1 ± 19.4% vs. 72.3 ± 18.2% vs. 60.2 ± 18.5%, p < 0.001)
Prasugrel monotherapy in T2DM provided potent platelet inhibition and reduced levels of a number of platelet-associated micro ribonucleic acid (miRNA). miR-197 is a potential marker of cardiovascular disease in this population
Summary
Despite increased atherothrombotic risk in type 2 diabetes mellitus, (T2DM) the best preventative antithrombotic strategy remains undetermined. Thrombotic events are associated with a large burden of morbidity and mortality in the general population [1], with an even higher risk in patients with type 2 diabetes mellitus (T2DM) [2]. Following coronary ischaemia requiring percutaneous intervention, prasugrel has shown enhanced vascular protective properties compared with clopidogrel in T2DM patients without an increase in bleeding risk, in contrast to individuals without T2DM [8, 9]. In the clopidogrel vs aspirin in patients at risk of ischemic events (CAPRIE) study, clopidogrel, used as single antiplatelet therapy (SAPT) showed better protection against vascular ischaemia compared with aspirin monotherapy in patients with T2DM [10], an effect that was even more pronounced in insulin-treated subjects [11]. Prasugrel as SAPT has not been well studied and data on patients with T2DM are scarce
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