Protease-activated receptor-mediated platelet aggregation in patients with type 2 diabetes on potent P2Y12 inhibitors.

Abstract

BackgroundAntiplatelet therapy is a cornerstone in the secondary prevention of ischemic events following percutaneous coronary intervention (PCI). The new P2Y12 receptor inhibitors prasugrel and ticagrelor have been shown to improve patients' outcomes. Whether or not these drugs have equal efficacy in individuals with or without diabetes is disputed. Furthermore, platelets can be activated by thrombin, which is, at least in part, independent of P2Y12‐mediated platelet activation. Protease‐activated receptor (PAR)‐1 and −4 are thrombin receptors on human platelets. We sought to compare the in vitro efficacy of prasugrel (n = 121) and ticagrelor (n = 99) to inhibit PAR‐mediated platelet aggregation in individuals with type 2 diabetes (prasugrel n = 26, ticagrelor n = 29).Materials and MethodsWe 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.ResultsOverall, there were no differences of P2Y12‐, PAR‐1‐ and PAR‐4‐mediated platelet aggregation between prasugrel‐ and ticagrelor‐treated patients. However, both drugs inhibited P2Y12‐mediated platelet aggregation stronger, and thereby to a similar extent in patients with type 2 diabetes than in those without diabetes. There was no correlation between either P2Y12‐, or PAR‐1‐ or PAR‐4‐mediated platelet aggregation and levels of HbA1c or the body mass index (BMI). However, we observed patients with high residual platelet reactivity in response to PAR‐1 and PAR‐4 stimulation in all cohorts.ConclusionPrasugrel and ticagrelor inhibit P2Y12‐ and PAR‐mediated platelet aggregation in individuals with diabetes to a similar extent, irrespective of HbA1c levels and BMI.