Protease-Activated Receptor-Mediated Platelet Aggregation In Patients With Type 2 Diabetes On Potent P2Y12 Inhibitors
Abstract Background: Dual antiplatelet therapy is a cornerstone in the secondary prevention of ischemic events following percutaneous coronary intervention (PCI) with stent implantation. The new, more potent adenosine diphosphate (ADP) P2Y12 receptor inhibitors prasugrel and ticagrelor have been shown to improve patients’ outcomes. Whether or not these drugs have equal efficacy in diabetic as in non-diabetic individuals is disputed. Furthermore, platelets can be activated by thrombin, which is, at least in part, independent of ADP-inducible activation. Protease-activated receptor (PAR)-1 and -4 are thrombin receptors on human platelets activated by the agonists SFLLRN and AYPGKF, respectively. In the current study, we sought to compare the in vitro efficacy of prasugrel (n=121) and ticagrelor (n=99) to inhibit PAR-mediated platelet activation in patients with type 2 diabetes (n=55).Materials and Methods: We compared P2Y12-, PAR-1- and PAR-4-mediated platelet aggregation as assessed by multiple electrode platelet aggregometry between prasugrel- and ticagrelor-treated patients without and with type 2 diabetes who underwent acute PCI. Results: There were no significant differences of on-treatment platelet aggregation in response to ADP, SFLLRN and AYPGKF between patients on prasugrel or on ticagrelor. Diabetic and non-diabetic patients responded equally. There was no significant correlation between either; ADP-, SFLLRN-, or AYPGKF-inducible platelet aggregation and levels of HbA1c or the body mass index. However, we observed patients with high residual platelet reactivity to SFLLRN and AYPGKF in all cohorts.Conclusion: Prasugrel and ticagrelor inhibit platelet aggregation in diabetic and non-diabetic patients to a similar extent.