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3 Ticagrelor has a beneficial synergistic relationship with endothelial vasodilators in patients with coronary disease
  1. Jennifer A Rossington1,
  2. Khalid M Naseem2,
  3. Benjamin Spurgeon2,
  4. Angela Hoye1
  1. 1Academic Cardiology, Hull York Medical School, Castle Hill Hospital
  2. 2Thrombosis Laboratory, Hull York Medical School, University of Hull


Introduction Endogenous 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.

Methods Participants 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)).

Results Sixty-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).

Conclusion P2Y12 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.

Abstract 3 Figure 1

Evidence of synergism between endothelial vasodilators and ticagrelor following platelet activation (PAR1 agonist 10 µM). A: histogram demonstrating the percentage of platelet inhibition in whole blood (WB) with increasing concentrations of PGI2 and in platelet rich plasma with increasing concentrations of GSNO. Significantly greater inhibition of p-selection expression was seen following ticagrelor, statistically beyond the expected additive effect B: histogram of VASP phosphorylation associated fluorescence (median fluorescence intensity) fold change from unstimulated baseline in response to PGI2. No effect demonstrated by ticagrelor alone but a statistically greater fold change seen in response to PGI2post ticagrelor administration C: dose response curve to PGI2 showing percentage formation of platelet leukocyte aggregates. No significant difference seen in the absence of PGI2 however an important reduction in percentage post ticagrelor with the addition of PGI2.All measurements at baseline (solid bar/black line) and post three days of ticagrelor (open bar/grey line). Error bars to one standard deviation. **p value<0.001; *p value<0.003

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