Physicians' Academy for Cardiovascular Education

Potent P2Y12 receptor inhibitor shows stronger antithrombotic effect in T2DM patients with CVD

A randomized, cross-over study showed a stronger antiplatelet effect and a faster and more potent antithrombotic effect with ticagrelor than with clopidogrel in T2DM patients with stable CVD.

Literature - Zafar MU, Baber U, Smith DA, et al. - Thromb Haemost 2017, published online ahead of print


Type 2 diabetes (T2DM) patients have a high risk of CV morbidity and mortality, which is partly caused by platelet hyperreactivity [1-3]. Inhibition of the P2Y12 receptor by antiplatelet therapy has shown great clinical benefits in the prevention of secondary coronary events in CVD patients [4,5]. However, data on the effects in T2DM patients are limited and usually obtained from subgroup analyses [6]. Available studies show that in addition to increased platelet reactivity, patients respond less to antiplatelet therapy than non-diabetic patients. The PLATO trial demonstrated a faster and significant reduction in CV events in ACS patients treated with ticagrelor compared to clopidogrel. Although results in the diabetic subgroup were similar, no significance was detected [7].

A randomized, cross-over, open-label, 2-treatment trial in T2DM patients with stable CVD was conducted. Patients (n=20) were treated with both therapies, consisting of either ticagrelor or clopidogrel, with a 2-week washout period in between, and randomized to one of the two treatment sequences. Patients received a loading-dose plus one week of daily therapy of each treatment. Antithrombotic effects were measured in an ex vivo model in which non-anticoagulated blood is perfused over a thrombogenic substrate. The difference between thrombus areas before and after the intervention is a measure for the antithrombotic effect of the study treatment. Platelet function was assessed with multiple electrode aggregometry, in which adenosine diphosphate triggers platelet aggregation via the P2Y12-receptor pathway. Moreover, VerifyNow was used to assess aggregation in whole blood treated with the P2Y12-receptor inhibitors, using light transmittance.

Main results


This randomized, cross-over trial demonstrated that treatment with ticagrelor resulted in a stronger inhibition of platelet aggregation, and more importantly, a more potent antithrombotic effect than clopidogrel in T2DM patients with stable CVD.


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