3 Ticagrelor has a beneficial synergistic relationship with endothelial vasodilators in patients with coronary disease

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IntroductionEndogenous endothelial vasodilators and ticagrelor both vasodilate and inhibit platelets. This study evaluated a potential mechanistic interaction between ticagrelor and endothelial vasodilators in patients with stable coronary disease.MethodsParticipants were assessed at baseline and after 3 days of ticagrelor. Blood samples were incubated with nitric oxide (GSNO) donor or prostacyclin (PGI2) and then maximally activated. Using flow cytometry, P-selectin, VASP phosphorylation (-P) and platelet leukocyte aggregate (PLA) associated fluorescence were quantified as measures of platelet activation. EndoPAT measured endothelial function (reactive hyperaemic index (RHI)).ResultsSixty-three patients were included. There was a synergistic relationship between ticagrelor and both vasodilators (GSNO and PGI2) (Figure). VASP-P, as evidence of signalling, was significantly increased in platelets post ticagrelor. PLA results were consistent and showed a greater response to prostacyclin after ticagrelor. RHI increased post ticagrelor (1.91 to 2.04 p=0.049). The magnitude of RHI increase positively correlated to the extent of platelet inhibition by ticagrelor (p=0.014).ConclusionP2Y12 inhibition by ticagrelor enhances the antiplatelet effects of endothelial vasodilators and endothelial function. The extent of endothelial improvement can predict the anti-platelet response to ticagrelor.

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